Hepatology

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

A version of this article first appeared on Medscape.com.

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

A version of this article first appeared on Medscape.com.

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

A version of this article first appeared on Medscape.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

Industry payments to U.S. gastroenterologists and hepatologists increased from 2014 to 2016 before beginning to steadily decrease after 2016, but they're largely concentrated among a small few, according to new research published in Gastroenterology.

South_agency/Getty Images

The study aimed to identify trends in these specialties in the years after the Sunshine Act, enacted in 2010, and the federal program Open Payments, established in 2013.

“Although Open Payments launched in September of 2014, all the joinpoints in our study occurred more than a year later in 2016, suggesting a delay in observable changes in behavior on industry physician relationships,” wrote Xiaohan Ying, MD, of Weill Cornell Medicine in New York, and colleagues. “Since 2016, we have seen a sustained reduction in general industry payments to physicians while research payments remained stable, which is likely the desired outcome of this program.”

That’s also the conclusion of Lawrence Kosinski, MD, MBA, a spokesperson for the American Gastroenterological Association, who was not involved in the study.

“Most all of us are aware of the Sunshine Act and have reacted accordingly, so I am not surprised that reimbursement per physician has declined over the time period,” Dr. Kosinski told this news organization. “Many physicians are very sensitive to their reporting and have decreased their exposures,” said Dr. Kosinski, founder of SonarMD and a member of the Health & Human Services Advisory Committee on Value-Based Payment. “What does surprise me is the marked disparity in payments with a very small number of physicians receiving tremendous reimbursement from speaking engagements and promotions.”

The researchers retrospectively analyzed industry payments to 26,981 practicing pediatric and adults gastroenterologists and hepatologists using the National Plan and Provider Enumeration System and data from Open Payments between January 2014 and December 2020. The researchers excluded education payments and focused on general payments, which “include charitable contribution, speaker fees, consulting fees, ownership and investments, education, entertainment, food and beverages, gift, honoraria, royalty and license, and travel and lodging,” they reported.
 

Who gets paid, and how much?

While $27.5 million was going to research and grants, most of the payments ($403.3 million) were general payments; out of the total payments to specialists, $30 million went to hepatology, and $400.8 million went to gastroenterology. Nearly all of the general payments ($398.1 million) were for noneducation purposes; 90.5% of general payments went to men and 9.5% went to women, at an average of $17,167 per person. Nearly half the payments (43.8%) were for speaker fees, totaling $174.3 million, followed by 18.4% going to consulting ($73.1 million) and 12.9% going to food and beverages ($51.5 million).

Most of the physicians accepting payments (86.6%) received less than $10,000, but this made up only 8.3% of all payments. Meanwhile, 74% of all the payments, $294.6 million, went to just 3.1% of the physicians, all of whom received more than $100,000.

That breakdown is what most caught Dr. Kosinki’s attention.

“It’s one thing for a speaker to declare that they are receiving funds from pharma, but they never let us know how much,” Dr. Kosinski said. “Some of these speakers are realizing a very significant payment, which could change the opinions of those listening to their presentations.”

The authors reported that a group of 50 top earners (0.2%) received more than $1 million between 2014 and 2020. Their payments totaled $94.8 million and accounted for nearly a quarter (23.8%) of all the payments. All but one of these physicians were men, and one physician has received more than $1 million every year since 2014.
 

Payments for guideline authors explored

The authors examined payments to practicing U.S. gastroenterologists and hepatologists who helped write clinical guidelines for the following organizations:

• American Gastroenterological Association (AGA).
• American College of Gastroenterology (ACG).
• American Association for the Study of Liver Disease (AASLD).
• North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).
• American Society for Gastrointestinal Endoscopy (ASGE).

The 186 guidelines published between 2014 and 2020 had 632 physician authors, 415 of whom were practicing gastroenterologists and hepatologists in the United States. Most of these physicians (85.8%) received at least one industry payment, with payments to guideline authors totaling $43.6 million.

Similar to the lopsided breakdown for total payments across all physicians, the majority of the payments (87.4%, or $38.1 million) went to one-quarter of the authors, who each received more than $100,000 per person. Meanwhile, 38.2% of the guideline authors received less than $10,000.

“However, these numbers are likely to decrease in the future as professional societies, such as AASLD, require a majority of the guideline authors to be free of conflict of interest relevant to the subject matter,” the authors wrote. They added that members selected as part of the AGA’s guideline development group (GDG) must report all conflicts of interest, including indirect and intellectual ones, and are recused or excluded when appropriate. These guideline development group participants must also forgo speaking and consulting arrangements until one year after the guideline’s publication.
 

Trends have been shifting

Total industry payments initially grew at a rate of 11.4% a year between 2014 and 2016 before decreasing at a rate of 5.8% per year after 2016 (P = .03). Though a similar trend occurred at the individual level, it did not reach significance.

However, the trend differed slightly between men and women: Payments to men increased 10.4% annually until 2016 then decreased 6.8% per year thereafter, but women’s payments increased 11.3% per year until 2019. Between 2014 and 2019, the amount per person payment dropped 3.5% annually to physicians overall, but payments to women initially increased 35.4% a year between 2014 and 2016 before decreasing.

Although not statistically significant, trends for types of payments showed that speaker and food/beverage fees have been declining since 2016 while consulting fees have been declining since 2014.

“The reduction in industry payments could be due to the Hawthorne effect, where physicians alter their behavior after becoming aware that their payments were being monitored,” the authors wrote. “Although many physicians see themselves as less vulnerable to be biased by industry compensation, studies have shown that even small payments can affect behavior such as prescription pattern. Additionally, studies have found that patients are less likely to trust physicians who have received industry payments.”

The authors acknowledged the role of industry payments in funding clinical trials but noted that pharmaceutical companies themselves have been taking on more design and execution of trials in recent decades. Further, only 6% of all payments went to research and grant funding, a little more than half the payments for food and beverages.

“While industry research funding is undeniably crucial, it simply plays a very small role in total industry compensation for physicians,” the authors wrote. “While speaker events could be beneficial and educational for physicians and other audiences, these events could also be utilized as means to promote specific products. While it is beneficial to seek input from experienced gastroenterologists for novel therapies and devices, actions should be taken to place limitations on industry payments to physicians, especially for the top earners.”

One author reported speaker fees from W.L. Gore & Associates and Cook Medical. The other two others had no disclosures. No external funding was noted. Dr. Kosinski reported having no relevant disclosures.

This article was updated Aug. 9, 2022.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.

Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.

In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.

Sebastian Kaulitzki/Science Photo Library

However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
 

Not all bad news

The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.

There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.

Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).

However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”

Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.

“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
 

A note of caution for early LT

About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.

“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.

He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.

Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.

The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.

Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.

Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.

In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.

Sebastian Kaulitzki/Science Photo Library

However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
 

Not all bad news

The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.

There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.

Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).

However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”

Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.

“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
 

A note of caution for early LT

About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.

“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.

He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.

Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.

The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.

Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.

Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.

In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.

Sebastian Kaulitzki/Science Photo Library

However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
 

Not all bad news

The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.

There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.

Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).

However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”

Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.

“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
 

A note of caution for early LT

About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.

“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.

He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.

Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.

The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.