Liver Disease

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

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

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

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

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

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

People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.

A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.

Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.

“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”

The study was published in Hepatology Communications.
 

More evidence for clinical relevance of MAFLD

The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.

NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.

“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”

In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.

Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.

The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
 

Sorting COVID outcomes by liver steatosis

To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.

They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.

The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.

The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).

They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.

The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).

The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).

For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)

Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.

That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
 

Next steps and new questions

Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.

The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.

“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.

Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.

Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”

The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.

Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.

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

People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.

A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.

Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.

“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”

The study was published in Hepatology Communications.
 

More evidence for clinical relevance of MAFLD

The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.

NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.

“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”

In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.

Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.

The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
 

Sorting COVID outcomes by liver steatosis

To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.

They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.

The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.

The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).

They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.

The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).

The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).

For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)

Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.

That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
 

Next steps and new questions

Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.

The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.

“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.

Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.

Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”

The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.

Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.

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

People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.

A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.

Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.

“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”

The study was published in Hepatology Communications.
 

More evidence for clinical relevance of MAFLD

The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.

NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.

“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”

In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.

Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.

The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
 

Sorting COVID outcomes by liver steatosis

To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.

They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.

The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.

The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).

They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.

The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).

The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).

For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)

Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.

That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
 

Next steps and new questions

Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.

The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.

“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.

Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.

Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”

The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.

Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.

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

For injection drug users with hepatitis C virus (HCV) infection, providing treatment opportunities within a local needle exchange program can provide care to more patients and eventually cure more patients, a new study suggests.

The study’s findings help “counteract the implicit belief within the medical community that people who inject drugs can’t or don’t want to engage in health care,” lead author Benjamin Eckhardt, MD, with NYU Grossman School of Medicine, told this news organization.

“By simply focusing on patient accompaniment, limiting stigma, and removing the punitive response for missed appointments, we can effectively engage people who inject drugs in health care and more specifically cure their infection, making significant inroads to HCV elimination,” Dr. Eckhardt said.

The study was published online  in JAMA Internal Medicine.
 

Nonjudgmental, patient-centered approach

Researchers included 165 injection drug users with HCV (mean age, 42 years; 78% men); 82 were randomly allocated to the accessible care intervention and 83 to a usual care control group.

The accessible care model provides HCV treatment within a community-based needle exchange program in a comfortable, nonjudgmental atmosphere, “without fear of shame or stigma that people who inject drugs often experience in mainstream institutions,” the investigators explain.

Control participants were connected to a patient navigator who facilitated referrals to community direct antigen antiviral therapy programs that were not at a syringe service program.

In an intent-to-treat analysis, those enrolled in the accessible care group achieved sustained viral eradication at 12 months at significantly higher rates than those in the control group (67% vs. 23%; P < .001).

Once patients initiated treatment, cure rates were the same in both groups (86%), indicating that the major benefit of the accessible care program was in facilitating treatment, rather than increasing adherence to or response to treatment, the researchers noted.

This is reflected in the fact that the percentage of participants who advanced along the care cascade was significantly higher at each step for the accessible care group than the control group, from referral to an HCV clinician (93% vs. 45%), attendance of the initial HCV clinical visit (87% vs. 37%), completion of baseline laboratory testing (87% vs. 31%), and treatment initiation (78% vs. 27%).
 

Getting to the population in need

“The most surprising aspect of the study was how successful we were at recruiting, engaging, and treating people who inject drugs who lived outside the immediate community where the syringe exchange program was located and had no prior connection to the program,” Dr. Eckhardt said.

“We had numerous individuals travel 45-plus minutes on the subway from the South Bronx, passing four major medical centers with robust hepatitis C treatment programs, to seek care for hepatitis C in a small, dark office – but also an office they’d heard can be trusted – without fear of stigma or preconditions,” Dr. Eckhardt said.

Commenting on the study’s findings, Nancy Reau, MD, section chief of hepatology at Rush Medical College, Chicago, said, “This is another successful example of making therapy accessible to the population who is in need versus trying to move them into a tertiary care model.”

Dr. Reau noted that similar care models exist in the United States but are not always accessible to the population in need.

“The safety and efficacy of current therapy and the simplified care cascade make HCV an appropriate disease for this delivery,” she said, adding that this study “highlights not just the importance of these programs but also the necessity of engaging the medical community, changing policy, and using patient navigators and monetary support/prioritization to provide appropriate HCV management to those who are at high risk for the disease and for transmission.”
 

Accessible care beyond HCV

The coauthors of an accompanying editor’s note point out that the treatment for HCV has improved substantially, but it can be a real challenge to provide treatment to injection drug users because the U.S. health care system is not oriented toward the needs of this population.

“It is not surprising that the accessible care arm achieved a higher rate of viral eradication, as it created a patient-focused experience,” write Asha Choudhury, MD, MPH, with the University of California, San Francisco, and Mitchell Katz, MD, with NYC Health and Hospitals. “Creating inviting and engaging environments is particularly important when caring for patients from stigmatized groups. Having more sites that are accessible and inclusive like this for treating patients will likely increase treatment of hepatitis C.”

In their view, the study raises “two dueling questions: Is this model replicable across the U.S.? And, conversely, why isn’t all medical care offered in friendly, nonjudgmental settings with the intention of meeting patient goals?”

They conclude that the study’s lessons extend beyond this particular population and have implications for the field at large.

“The model is replicable to the extent that health care systems are prepared to provide nonjudgmental supportive care for persons who inject drugs,” they write. “However, all patients would benefit from a health care system that provided more patient-centered environments.”

The study was funded by the National Institute on Drug Abuse. Dr. Eckhardt reports receiving grants from the National Institutes of Health and Gilead during the conduct of the study. Dr. Choudhury, Dr. Katz, and Dr. Reau report no relevant financial relationships.

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

For injection drug users with hepatitis C virus (HCV) infection, providing treatment opportunities within a local needle exchange program can provide care to more patients and eventually cure more patients, a new study suggests.

The study’s findings help “counteract the implicit belief within the medical community that people who inject drugs can’t or don’t want to engage in health care,” lead author Benjamin Eckhardt, MD, with NYU Grossman School of Medicine, told this news organization.

“By simply focusing on patient accompaniment, limiting stigma, and removing the punitive response for missed appointments, we can effectively engage people who inject drugs in health care and more specifically cure their infection, making significant inroads to HCV elimination,” Dr. Eckhardt said.

The study was published online  in JAMA Internal Medicine.
 

Nonjudgmental, patient-centered approach

Researchers included 165 injection drug users with HCV (mean age, 42 years; 78% men); 82 were randomly allocated to the accessible care intervention and 83 to a usual care control group.

The accessible care model provides HCV treatment within a community-based needle exchange program in a comfortable, nonjudgmental atmosphere, “without fear of shame or stigma that people who inject drugs often experience in mainstream institutions,” the investigators explain.

Control participants were connected to a patient navigator who facilitated referrals to community direct antigen antiviral therapy programs that were not at a syringe service program.

In an intent-to-treat analysis, those enrolled in the accessible care group achieved sustained viral eradication at 12 months at significantly higher rates than those in the control group (67% vs. 23%; P < .001).

Once patients initiated treatment, cure rates were the same in both groups (86%), indicating that the major benefit of the accessible care program was in facilitating treatment, rather than increasing adherence to or response to treatment, the researchers noted.

This is reflected in the fact that the percentage of participants who advanced along the care cascade was significantly higher at each step for the accessible care group than the control group, from referral to an HCV clinician (93% vs. 45%), attendance of the initial HCV clinical visit (87% vs. 37%), completion of baseline laboratory testing (87% vs. 31%), and treatment initiation (78% vs. 27%).
 

Getting to the population in need

“The most surprising aspect of the study was how successful we were at recruiting, engaging, and treating people who inject drugs who lived outside the immediate community where the syringe exchange program was located and had no prior connection to the program,” Dr. Eckhardt said.

“We had numerous individuals travel 45-plus minutes on the subway from the South Bronx, passing four major medical centers with robust hepatitis C treatment programs, to seek care for hepatitis C in a small, dark office – but also an office they’d heard can be trusted – without fear of stigma or preconditions,” Dr. Eckhardt said.

Commenting on the study’s findings, Nancy Reau, MD, section chief of hepatology at Rush Medical College, Chicago, said, “This is another successful example of making therapy accessible to the population who is in need versus trying to move them into a tertiary care model.”

Dr. Reau noted that similar care models exist in the United States but are not always accessible to the population in need.

“The safety and efficacy of current therapy and the simplified care cascade make HCV an appropriate disease for this delivery,” she said, adding that this study “highlights not just the importance of these programs but also the necessity of engaging the medical community, changing policy, and using patient navigators and monetary support/prioritization to provide appropriate HCV management to those who are at high risk for the disease and for transmission.”
 

Accessible care beyond HCV

The coauthors of an accompanying editor’s note point out that the treatment for HCV has improved substantially, but it can be a real challenge to provide treatment to injection drug users because the U.S. health care system is not oriented toward the needs of this population.

“It is not surprising that the accessible care arm achieved a higher rate of viral eradication, as it created a patient-focused experience,” write Asha Choudhury, MD, MPH, with the University of California, San Francisco, and Mitchell Katz, MD, with NYC Health and Hospitals. “Creating inviting and engaging environments is particularly important when caring for patients from stigmatized groups. Having more sites that are accessible and inclusive like this for treating patients will likely increase treatment of hepatitis C.”

In their view, the study raises “two dueling questions: Is this model replicable across the U.S.? And, conversely, why isn’t all medical care offered in friendly, nonjudgmental settings with the intention of meeting patient goals?”

They conclude that the study’s lessons extend beyond this particular population and have implications for the field at large.

“The model is replicable to the extent that health care systems are prepared to provide nonjudgmental supportive care for persons who inject drugs,” they write. “However, all patients would benefit from a health care system that provided more patient-centered environments.”

The study was funded by the National Institute on Drug Abuse. Dr. Eckhardt reports receiving grants from the National Institutes of Health and Gilead during the conduct of the study. Dr. Choudhury, Dr. Katz, and Dr. Reau report no relevant financial relationships.

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

For injection drug users with hepatitis C virus (HCV) infection, providing treatment opportunities within a local needle exchange program can provide care to more patients and eventually cure more patients, a new study suggests.

The study’s findings help “counteract the implicit belief within the medical community that people who inject drugs can’t or don’t want to engage in health care,” lead author Benjamin Eckhardt, MD, with NYU Grossman School of Medicine, told this news organization.

“By simply focusing on patient accompaniment, limiting stigma, and removing the punitive response for missed appointments, we can effectively engage people who inject drugs in health care and more specifically cure their infection, making significant inroads to HCV elimination,” Dr. Eckhardt said.

The study was published online  in JAMA Internal Medicine.
 

Nonjudgmental, patient-centered approach

Researchers included 165 injection drug users with HCV (mean age, 42 years; 78% men); 82 were randomly allocated to the accessible care intervention and 83 to a usual care control group.

The accessible care model provides HCV treatment within a community-based needle exchange program in a comfortable, nonjudgmental atmosphere, “without fear of shame or stigma that people who inject drugs often experience in mainstream institutions,” the investigators explain.

Control participants were connected to a patient navigator who facilitated referrals to community direct antigen antiviral therapy programs that were not at a syringe service program.

In an intent-to-treat analysis, those enrolled in the accessible care group achieved sustained viral eradication at 12 months at significantly higher rates than those in the control group (67% vs. 23%; P < .001).

Once patients initiated treatment, cure rates were the same in both groups (86%), indicating that the major benefit of the accessible care program was in facilitating treatment, rather than increasing adherence to or response to treatment, the researchers noted.

This is reflected in the fact that the percentage of participants who advanced along the care cascade was significantly higher at each step for the accessible care group than the control group, from referral to an HCV clinician (93% vs. 45%), attendance of the initial HCV clinical visit (87% vs. 37%), completion of baseline laboratory testing (87% vs. 31%), and treatment initiation (78% vs. 27%).
 

Getting to the population in need

“The most surprising aspect of the study was how successful we were at recruiting, engaging, and treating people who inject drugs who lived outside the immediate community where the syringe exchange program was located and had no prior connection to the program,” Dr. Eckhardt said.

“We had numerous individuals travel 45-plus minutes on the subway from the South Bronx, passing four major medical centers with robust hepatitis C treatment programs, to seek care for hepatitis C in a small, dark office – but also an office they’d heard can be trusted – without fear of stigma or preconditions,” Dr. Eckhardt said.

Commenting on the study’s findings, Nancy Reau, MD, section chief of hepatology at Rush Medical College, Chicago, said, “This is another successful example of making therapy accessible to the population who is in need versus trying to move them into a tertiary care model.”

Dr. Reau noted that similar care models exist in the United States but are not always accessible to the population in need.

“The safety and efficacy of current therapy and the simplified care cascade make HCV an appropriate disease for this delivery,” she said, adding that this study “highlights not just the importance of these programs but also the necessity of engaging the medical community, changing policy, and using patient navigators and monetary support/prioritization to provide appropriate HCV management to those who are at high risk for the disease and for transmission.”
 

Accessible care beyond HCV

The coauthors of an accompanying editor’s note point out that the treatment for HCV has improved substantially, but it can be a real challenge to provide treatment to injection drug users because the U.S. health care system is not oriented toward the needs of this population.

“It is not surprising that the accessible care arm achieved a higher rate of viral eradication, as it created a patient-focused experience,” write Asha Choudhury, MD, MPH, with the University of California, San Francisco, and Mitchell Katz, MD, with NYC Health and Hospitals. “Creating inviting and engaging environments is particularly important when caring for patients from stigmatized groups. Having more sites that are accessible and inclusive like this for treating patients will likely increase treatment of hepatitis C.”

In their view, the study raises “two dueling questions: Is this model replicable across the U.S.? And, conversely, why isn’t all medical care offered in friendly, nonjudgmental settings with the intention of meeting patient goals?”

They conclude that the study’s lessons extend beyond this particular population and have implications for the field at large.

“The model is replicable to the extent that health care systems are prepared to provide nonjudgmental supportive care for persons who inject drugs,” they write. “However, all patients would benefit from a health care system that provided more patient-centered environments.”

The study was funded by the National Institute on Drug Abuse. Dr. Eckhardt reports receiving grants from the National Institutes of Health and Gilead during the conduct of the study. Dr. Choudhury, Dr. Katz, and Dr. Reau report no relevant financial relationships.

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

Compared with White people, Black people are less likely to develop cirrhosis from nonalcoholic steatohepatitis (NASH) but are more likely to die when hospitalized with this condition, researchers say.

The finding highlights the importance of addressing hepatic complications and nonhepatic comorbidities with a comprehensive and interdisciplinary approach that includes social determinants of health, said Emad Qayed, MD, MPH, an associate professor of medicine at Emory University School of Medicine, Atlanta.

“Clinicians should realize that in Black patients with NASH and NASH cirrhosis, mortality can be high despite a low rate of hepatic complications,” he told this news organization.

The study by Dr. Qayed and colleagues was published in the Journal of Clinical Gastroenterology.
 

A nationwide analysis

Previous studies have indicated that Black people are less likely than White people to develop nonalcoholic fatty liver disease (NAFLD), despite the fact that prevalence is increasing. Furthermore, when Black people do develop NAFLD, the disease is less likely to progress to NASH. In cases in which NASH does develop, the evidence has been mixed as to the effect of race on hospital outcomes.

To shed new light on that question, Dr. Qayed and colleagues analyzed data from 2016 to 2018 from the National Inpatient Sample, which is produced by the Healthcare Cost and Utilization Project and is sponsored by the Agency of Healthcare Research and Quality.

They identified 43,409 hospitalizations for NASH, with 41,143 White patients and 2,266 Black patients. The mean age of the Black patients was less than that of the White patients (56.4 years vs. 63.0 years), and Black patients were more likely to be women (69.9% vs. 61.6%).

More of the Black patients had hypertension, obesity, chronic kidney disease, and congestive heart failure, while more of the White patients had diabetes, dyslipidemia, and ischemic heart disease.

Among the Black patients, 33.6% had cirrhosis, compared with 56.4% of the White patients. Likewise, among the Black patients, there were fewer manifestations of decompensated cirrhosis, compared with the White patients. Black patients were also less likely to have had to undergo upper endoscopy and paracentesis.

The Black patients died in the hospital at a rate of 3.9%, which was not significantly higher than the 3.7% rate for the White patients (unadjusted odds ratio = 1.06; 95% confidence interval: 0.84-1.32; P = .6). But, when the researchers adjusted for age, sex, cirrhosis, risk of mortality (based on the overall number and severity of diseases), and insurance status, there were significantly higher odds of mortality among the Black patients (adjusted OR, 1.34; 95% CI: 1.05-1.71; P = .018).

They did not find any association between hospital size, location, or region with mortality.

They also found no difference in mortality between Black patients and White patients among those those with and those without cirrhosis. However, they found that Black patients were more likely to have acute kidney injury, chronic kidney disease, and congestive heart failure.

Regarding the reasons for hospitalization, the researchers found liver-related illnesses, such as hepatic failure and noninfectious hepatitis, to be most common among the White patients. Circulatory disorders, such as heart failure, and endocrine disorders, such as diabetes mellitus with complications, were found to be most common among the Black patients.

The length of time in the hospital was longer for the Black patients than the White patients (6.3 days vs. 5.6 days; P < .0001). The cost of hospitalization was higher for Black patients as well ($18,603 vs. $17,467). This suggests that Black patients were sicker overall, despite their lower rates of liver complications.

“Some of these differences are likely related to socioeconomic factors and clinical comorbidities, such as cardiac and renal disease,” Dr. Qayed said. “However, the underlying etiologies for such disparities in NASH and cirrhosis remain unclear. Further research is warranted to clarify these etiologies.”
 

NASH as part of the metabolic syndrome

“Clinicians should consider NASH as part of the metabolic syndrome,” Paul Martin, MD, chief of digestive health and liver diseases at the University of Miami, told this news organization. He was not involved in the study.

“Typically, these patients have a number of risk factors for fatty liver, including obesity and often hyperlipidemia, hypertension, and sleep apnea,” he said. “Clinicians should screen their patients for such comorbidities and then treat them.”

Genetic factors could also play a role in the difference in susceptibility to fatty liver disease found between Black and White patients, he added.

Dr. Martin noted a prevalence of fatty liver in many Hispanic populations and that it is found in Asia but sometimes in the absence of the risk factors associated with it in the United States.

Dr. Qayed and Dr. Martin reported no relevant financial relationships.

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

Compared with White people, Black people are less likely to develop cirrhosis from nonalcoholic steatohepatitis (NASH) but are more likely to die when hospitalized with this condition, researchers say.

The finding highlights the importance of addressing hepatic complications and nonhepatic comorbidities with a comprehensive and interdisciplinary approach that includes social determinants of health, said Emad Qayed, MD, MPH, an associate professor of medicine at Emory University School of Medicine, Atlanta.

“Clinicians should realize that in Black patients with NASH and NASH cirrhosis, mortality can be high despite a low rate of hepatic complications,” he told this news organization.

The study by Dr. Qayed and colleagues was published in the Journal of Clinical Gastroenterology.
 

A nationwide analysis

Previous studies have indicated that Black people are less likely than White people to develop nonalcoholic fatty liver disease (NAFLD), despite the fact that prevalence is increasing. Furthermore, when Black people do develop NAFLD, the disease is less likely to progress to NASH. In cases in which NASH does develop, the evidence has been mixed as to the effect of race on hospital outcomes.

To shed new light on that question, Dr. Qayed and colleagues analyzed data from 2016 to 2018 from the National Inpatient Sample, which is produced by the Healthcare Cost and Utilization Project and is sponsored by the Agency of Healthcare Research and Quality.

They identified 43,409 hospitalizations for NASH, with 41,143 White patients and 2,266 Black patients. The mean age of the Black patients was less than that of the White patients (56.4 years vs. 63.0 years), and Black patients were more likely to be women (69.9% vs. 61.6%).

More of the Black patients had hypertension, obesity, chronic kidney disease, and congestive heart failure, while more of the White patients had diabetes, dyslipidemia, and ischemic heart disease.

Among the Black patients, 33.6% had cirrhosis, compared with 56.4% of the White patients. Likewise, among the Black patients, there were fewer manifestations of decompensated cirrhosis, compared with the White patients. Black patients were also less likely to have had to undergo upper endoscopy and paracentesis.

The Black patients died in the hospital at a rate of 3.9%, which was not significantly higher than the 3.7% rate for the White patients (unadjusted odds ratio = 1.06; 95% confidence interval: 0.84-1.32; P = .6). But, when the researchers adjusted for age, sex, cirrhosis, risk of mortality (based on the overall number and severity of diseases), and insurance status, there were significantly higher odds of mortality among the Black patients (adjusted OR, 1.34; 95% CI: 1.05-1.71; P = .018).

They did not find any association between hospital size, location, or region with mortality.

They also found no difference in mortality between Black patients and White patients among those those with and those without cirrhosis. However, they found that Black patients were more likely to have acute kidney injury, chronic kidney disease, and congestive heart failure.

Regarding the reasons for hospitalization, the researchers found liver-related illnesses, such as hepatic failure and noninfectious hepatitis, to be most common among the White patients. Circulatory disorders, such as heart failure, and endocrine disorders, such as diabetes mellitus with complications, were found to be most common among the Black patients.

The length of time in the hospital was longer for the Black patients than the White patients (6.3 days vs. 5.6 days; P < .0001). The cost of hospitalization was higher for Black patients as well ($18,603 vs. $17,467). This suggests that Black patients were sicker overall, despite their lower rates of liver complications.

“Some of these differences are likely related to socioeconomic factors and clinical comorbidities, such as cardiac and renal disease,” Dr. Qayed said. “However, the underlying etiologies for such disparities in NASH and cirrhosis remain unclear. Further research is warranted to clarify these etiologies.”
 

NASH as part of the metabolic syndrome

“Clinicians should consider NASH as part of the metabolic syndrome,” Paul Martin, MD, chief of digestive health and liver diseases at the University of Miami, told this news organization. He was not involved in the study.

“Typically, these patients have a number of risk factors for fatty liver, including obesity and often hyperlipidemia, hypertension, and sleep apnea,” he said. “Clinicians should screen their patients for such comorbidities and then treat them.”

Genetic factors could also play a role in the difference in susceptibility to fatty liver disease found between Black and White patients, he added.

Dr. Martin noted a prevalence of fatty liver in many Hispanic populations and that it is found in Asia but sometimes in the absence of the risk factors associated with it in the United States.

Dr. Qayed and Dr. Martin reported no relevant financial relationships.

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

Compared with White people, Black people are less likely to develop cirrhosis from nonalcoholic steatohepatitis (NASH) but are more likely to die when hospitalized with this condition, researchers say.

The finding highlights the importance of addressing hepatic complications and nonhepatic comorbidities with a comprehensive and interdisciplinary approach that includes social determinants of health, said Emad Qayed, MD, MPH, an associate professor of medicine at Emory University School of Medicine, Atlanta.

“Clinicians should realize that in Black patients with NASH and NASH cirrhosis, mortality can be high despite a low rate of hepatic complications,” he told this news organization.

The study by Dr. Qayed and colleagues was published in the Journal of Clinical Gastroenterology.
 

A nationwide analysis

Previous studies have indicated that Black people are less likely than White people to develop nonalcoholic fatty liver disease (NAFLD), despite the fact that prevalence is increasing. Furthermore, when Black people do develop NAFLD, the disease is less likely to progress to NASH. In cases in which NASH does develop, the evidence has been mixed as to the effect of race on hospital outcomes.

To shed new light on that question, Dr. Qayed and colleagues analyzed data from 2016 to 2018 from the National Inpatient Sample, which is produced by the Healthcare Cost and Utilization Project and is sponsored by the Agency of Healthcare Research and Quality.

They identified 43,409 hospitalizations for NASH, with 41,143 White patients and 2,266 Black patients. The mean age of the Black patients was less than that of the White patients (56.4 years vs. 63.0 years), and Black patients were more likely to be women (69.9% vs. 61.6%).

More of the Black patients had hypertension, obesity, chronic kidney disease, and congestive heart failure, while more of the White patients had diabetes, dyslipidemia, and ischemic heart disease.

Among the Black patients, 33.6% had cirrhosis, compared with 56.4% of the White patients. Likewise, among the Black patients, there were fewer manifestations of decompensated cirrhosis, compared with the White patients. Black patients were also less likely to have had to undergo upper endoscopy and paracentesis.

The Black patients died in the hospital at a rate of 3.9%, which was not significantly higher than the 3.7% rate for the White patients (unadjusted odds ratio = 1.06; 95% confidence interval: 0.84-1.32; P = .6). But, when the researchers adjusted for age, sex, cirrhosis, risk of mortality (based on the overall number and severity of diseases), and insurance status, there were significantly higher odds of mortality among the Black patients (adjusted OR, 1.34; 95% CI: 1.05-1.71; P = .018).

They did not find any association between hospital size, location, or region with mortality.

They also found no difference in mortality between Black patients and White patients among those those with and those without cirrhosis. However, they found that Black patients were more likely to have acute kidney injury, chronic kidney disease, and congestive heart failure.

Regarding the reasons for hospitalization, the researchers found liver-related illnesses, such as hepatic failure and noninfectious hepatitis, to be most common among the White patients. Circulatory disorders, such as heart failure, and endocrine disorders, such as diabetes mellitus with complications, were found to be most common among the Black patients.

The length of time in the hospital was longer for the Black patients than the White patients (6.3 days vs. 5.6 days; P < .0001). The cost of hospitalization was higher for Black patients as well ($18,603 vs. $17,467). This suggests that Black patients were sicker overall, despite their lower rates of liver complications.

“Some of these differences are likely related to socioeconomic factors and clinical comorbidities, such as cardiac and renal disease,” Dr. Qayed said. “However, the underlying etiologies for such disparities in NASH and cirrhosis remain unclear. Further research is warranted to clarify these etiologies.”
 

NASH as part of the metabolic syndrome

“Clinicians should consider NASH as part of the metabolic syndrome,” Paul Martin, MD, chief of digestive health and liver diseases at the University of Miami, told this news organization. He was not involved in the study.

“Typically, these patients have a number of risk factors for fatty liver, including obesity and often hyperlipidemia, hypertension, and sleep apnea,” he said. “Clinicians should screen their patients for such comorbidities and then treat them.”

Genetic factors could also play a role in the difference in susceptibility to fatty liver disease found between Black and White patients, he added.

Dr. Martin noted a prevalence of fatty liver in many Hispanic populations and that it is found in Asia but sometimes in the absence of the risk factors associated with it in the United States.

Dr. Qayed and Dr. Martin reported no relevant financial relationships.

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

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in wait-list dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings in the May issue of Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and wait-list outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to one approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to wait-list dropout.

The wait-list dropout variable was defined by list removal because of death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waiting list.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waiting list. Between the 2003 and 2006 period, the median wait-list time was 123 days, but this median wait-list duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had two LRTs, 6.2% had three LRTs, and 2.2% had greater than or equal to four LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 wait-list days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for wait-list dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of wait-list dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio, 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of wait-list dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of wait-list dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waiting list between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in wait-list dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings in the May issue of Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and wait-list outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to one approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to wait-list dropout.

The wait-list dropout variable was defined by list removal because of death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waiting list.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waiting list. Between the 2003 and 2006 period, the median wait-list time was 123 days, but this median wait-list duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had two LRTs, 6.2% had three LRTs, and 2.2% had greater than or equal to four LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 wait-list days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for wait-list dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of wait-list dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio, 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of wait-list dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of wait-list dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waiting list between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in wait-list dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings in the May issue of Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and wait-list outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to one approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to wait-list dropout.

The wait-list dropout variable was defined by list removal because of death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waiting list.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waiting list. Between the 2003 and 2006 period, the median wait-list time was 123 days, but this median wait-list duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had two LRTs, 6.2% had three LRTs, and 2.2% had greater than or equal to four LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 wait-list days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for wait-list dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of wait-list dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio, 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of wait-list dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of wait-list dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waiting list between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

A new mouse model that better represents chronic infection with hepatitis B virus (HBV) in humans may lead to more effective antiviral therapies for HBV, according to investigators.

During human infection, HBV genomes take the form of covalently closed circular DNA (cccDNA), a structure that has thwarted effective antiviral therapy and, until now, creation of an accurate mouse model, reported lead author Zaichao Xu, PhD, of Wuhan (China) University and colleagues.

“As the viral persistence reservoir plays a central role in HBV infection, HBV cccDNA is the key obstacle for a cure,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

Although several previous mouse models have approximated this phenomenon with recombinant cccDNA-like molecules (rcccDNA), the present model is the first to achieve genuine cccDNA, which does not naturally occur in mice.

“Although rcccDNA supports persistent viral replication and antigen expression, the nature of rcccDNA may differ from authentic cccDNA, as additional sequences, like LoxP or attR, were inserted into the HBV genome,” the investigators noted.

The new model was created by first constructing an adeno-associated virus vector carrying a replication-deficient HBV1.04-fold genome (AAV-HBV1.04). When injected into mice, the vector led to cccDNA formation via ataxia-telangiectasia and Rad3-related protein (ATR)–mediated DNA damage response, a finding that was confirmed by blocking the same process with ATR inhibitors.

Immediately after injection, mice tested positive for both hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), with peak concentrations after either 4 or 8 weeks depending on dose. HBV DNA was also detected in serum after injection, and 50% of hepatocytes exhibited HBsAg and hepatitis B core protein (HBc) after 1 week. At week 66, HBsAg, HBeAg, and HBc were still detectable in the liver.

“The expression of HBc could only be observed in the liver, but not in other organs or tissues, suggesting that the AAV-HBV1.04 only targeted the mouse liver,” the investigators wrote.

Further experimentation involving known cccDNA-binding proteins supported the similarity between cccDNA in the mouse model and natural infection.

“These results suggested that the chromatinization and transcriptional activation of cccDNA formed in this model dose not differ from wild-type cccDNA formed through infection.”

Next, Dr. Xu and colleagues demonstrated that the infected mice could serve as a reliable model for antiviral research. One week after injection with the vector, mice were treated with entecavir, polyinosinic-polycytidylic acid (poly[I:C]), or phosphate-buffered saline (PBS; control). As anticipated, entecavir suppressed circulating HBV DNA, but not HBsAg, HBeAg, or HBV cccDNA, whereas treatment with poly(I:C) reduced all HBV markers.

“This novel mouse model will provide a unique platform for studying HBV cccDNA and developing novel antivirals to achieve HBV cure,” the investigators concluded.

The study was supported by the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, Hubei Province’s Outstanding Medical Academic Leader Program, and others. The investigators reported no conflicts of interest.

A new mouse model that better represents chronic infection with hepatitis B virus (HBV) in humans may lead to more effective antiviral therapies for HBV, according to investigators.

During human infection, HBV genomes take the form of covalently closed circular DNA (cccDNA), a structure that has thwarted effective antiviral therapy and, until now, creation of an accurate mouse model, reported lead author Zaichao Xu, PhD, of Wuhan (China) University and colleagues.

“As the viral persistence reservoir plays a central role in HBV infection, HBV cccDNA is the key obstacle for a cure,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

Although several previous mouse models have approximated this phenomenon with recombinant cccDNA-like molecules (rcccDNA), the present model is the first to achieve genuine cccDNA, which does not naturally occur in mice.

“Although rcccDNA supports persistent viral replication and antigen expression, the nature of rcccDNA may differ from authentic cccDNA, as additional sequences, like LoxP or attR, were inserted into the HBV genome,” the investigators noted.

The new model was created by first constructing an adeno-associated virus vector carrying a replication-deficient HBV1.04-fold genome (AAV-HBV1.04). When injected into mice, the vector led to cccDNA formation via ataxia-telangiectasia and Rad3-related protein (ATR)–mediated DNA damage response, a finding that was confirmed by blocking the same process with ATR inhibitors.

Immediately after injection, mice tested positive for both hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), with peak concentrations after either 4 or 8 weeks depending on dose. HBV DNA was also detected in serum after injection, and 50% of hepatocytes exhibited HBsAg and hepatitis B core protein (HBc) after 1 week. At week 66, HBsAg, HBeAg, and HBc were still detectable in the liver.

“The expression of HBc could only be observed in the liver, but not in other organs or tissues, suggesting that the AAV-HBV1.04 only targeted the mouse liver,” the investigators wrote.

Further experimentation involving known cccDNA-binding proteins supported the similarity between cccDNA in the mouse model and natural infection.

“These results suggested that the chromatinization and transcriptional activation of cccDNA formed in this model dose not differ from wild-type cccDNA formed through infection.”

Next, Dr. Xu and colleagues demonstrated that the infected mice could serve as a reliable model for antiviral research. One week after injection with the vector, mice were treated with entecavir, polyinosinic-polycytidylic acid (poly[I:C]), or phosphate-buffered saline (PBS; control). As anticipated, entecavir suppressed circulating HBV DNA, but not HBsAg, HBeAg, or HBV cccDNA, whereas treatment with poly(I:C) reduced all HBV markers.

“This novel mouse model will provide a unique platform for studying HBV cccDNA and developing novel antivirals to achieve HBV cure,” the investigators concluded.

The study was supported by the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, Hubei Province’s Outstanding Medical Academic Leader Program, and others. The investigators reported no conflicts of interest.

A new mouse model that better represents chronic infection with hepatitis B virus (HBV) in humans may lead to more effective antiviral therapies for HBV, according to investigators.

During human infection, HBV genomes take the form of covalently closed circular DNA (cccDNA), a structure that has thwarted effective antiviral therapy and, until now, creation of an accurate mouse model, reported lead author Zaichao Xu, PhD, of Wuhan (China) University and colleagues.

“As the viral persistence reservoir plays a central role in HBV infection, HBV cccDNA is the key obstacle for a cure,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

Although several previous mouse models have approximated this phenomenon with recombinant cccDNA-like molecules (rcccDNA), the present model is the first to achieve genuine cccDNA, which does not naturally occur in mice.

“Although rcccDNA supports persistent viral replication and antigen expression, the nature of rcccDNA may differ from authentic cccDNA, as additional sequences, like LoxP or attR, were inserted into the HBV genome,” the investigators noted.

The new model was created by first constructing an adeno-associated virus vector carrying a replication-deficient HBV1.04-fold genome (AAV-HBV1.04). When injected into mice, the vector led to cccDNA formation via ataxia-telangiectasia and Rad3-related protein (ATR)–mediated DNA damage response, a finding that was confirmed by blocking the same process with ATR inhibitors.

Immediately after injection, mice tested positive for both hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), with peak concentrations after either 4 or 8 weeks depending on dose. HBV DNA was also detected in serum after injection, and 50% of hepatocytes exhibited HBsAg and hepatitis B core protein (HBc) after 1 week. At week 66, HBsAg, HBeAg, and HBc were still detectable in the liver.

“The expression of HBc could only be observed in the liver, but not in other organs or tissues, suggesting that the AAV-HBV1.04 only targeted the mouse liver,” the investigators wrote.

Further experimentation involving known cccDNA-binding proteins supported the similarity between cccDNA in the mouse model and natural infection.

“These results suggested that the chromatinization and transcriptional activation of cccDNA formed in this model dose not differ from wild-type cccDNA formed through infection.”

Next, Dr. Xu and colleagues demonstrated that the infected mice could serve as a reliable model for antiviral research. One week after injection with the vector, mice were treated with entecavir, polyinosinic-polycytidylic acid (poly[I:C]), or phosphate-buffered saline (PBS; control). As anticipated, entecavir suppressed circulating HBV DNA, but not HBsAg, HBeAg, or HBV cccDNA, whereas treatment with poly(I:C) reduced all HBV markers.

“This novel mouse model will provide a unique platform for studying HBV cccDNA and developing novel antivirals to achieve HBV cure,” the investigators concluded.

The study was supported by the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, Hubei Province’s Outstanding Medical Academic Leader Program, and others. The investigators reported no conflicts of interest.

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

People who don’t get enough sleep during the week may be able to reduce their risk for nonalcoholic fatty liver disease (NAFLD) by catching up on the weekends, researchers say.

“Our study revealed that people who get enough sleep have a lower risk of developing NAFLD than those who get insufficient sleep,” Sangheun Lee, MD, PhD, from Catholic Kwandong University, Incheon, South Korea, and colleagues wrote in Annals of Hepatology.

However, they cautioned that further research is needed to verify their finding.

Previous studies have associated insufficient sleep with obesity, hypertension, diabetes mellitus, and cardiovascular disease, as well as liver fibrosis.

A busy weekday schedule can make it harder to get enough sleep, and some people try to compensate by sleeping longer on weekends. Studies so far have produced mixed findings on this strategy, with some showing that more sleep on the weekend reduces the risk for obesity, hypertension, and metabolic syndrome, and others showing no effect on metabolic dysregulation or energy balance.
 

Accessing a nation’s sleep data

To explore the relationship between sleep patterns and NAFLD, Dr. Lee and colleagues analyzed data from Korea National Health and Nutrition Examination Surveys collected from 2008 to 2019. They excluded people aged less than 20 years, those with hepatitis B or C infections, liver cirrhosis or liver cancer, shift workers and others who “slept irregularly,” and those who consumed alcohol excessively, leaving a cohort of 101,138 participants.

The survey didn’t distinguish between sleep on weekdays and weekends until 2016, so the researchers divided their findings into two: 68,759 people surveyed from 2008 to 2015 (set 1) and 32,379 surveyed from 2016 to 2019 (set 2).

Set 1 was further divided into those who averaged more than 7 hours of sleep per day and those who slept less than that. Set 2 was divided into three groups: one that averaged less than 7 hours of sleep per day and did not catch up on weekends, one that averaged less than 7 hours of sleep per day and did catch up on weekends, and one that averaged more than 7 hours of sleep throughout the week.

The researchers used the hepatic steatosis index (HSI) to determine the presence of a fatty liver, calculated as 8 x (ratio of serum ALT to serum AST) + body mass index (+ 2 for female, + 2 in case of diabetes). An HSI of at least36 was considered an indicator of fatty liver.
 

Less sleep, more risk

Participants in set 1 slept for a mean of 6.8 hours, with 58.6% sleeping more than 7 hours a day. Those in set 2 slept a mean of 6.9 hours during weekdays, with 59.9% sleeping more than 7 hours. They also slept a mean of 7.7 hours on weekends.

In set 1, sleeping at least7 hours was associated with a 16% lower risk for NAFLD (odds ratio, 0.84; 95% confidence interval, 0.79-0.89).

In set 2, sleeping at least 7 hours on weekdays was associated with a 19% reduced risk for NAFLD (OR, 0.81; 95% CI, 0.74-0.89). Sleeping at least 7 hours on the weekend was associated with a 22% reduced risk for NAFLD (OR, 0.78; 95% CI, 0.70-0.87). Compared with those who slept less than 7 hours throughout the week, those who slept less than 7 hours on weekdays and more than 7 hours on weekends had a 20% lower rate of NAFLD (OR, 0.80; 95% CI, 0.70-0.92).

All these associations held true for both men and women.
 

Why getting your Z’s may have hepatic advantages

One explanation for the link between sleep patterns and NAFLD is that dysregulation of cortisol, inflammatory cytokines, and norepinephrine are associated with both variations in sleep and NAFLD onset, Dr. Lee and colleagues wrote.

They also pointed out that a lack of sleep can reduce the secretion of two hormones that promote satiety: leptin and glucagonlike peptide–1. As a result, people who sleep less may eat more and gain weight, which increases the risk for NAFLD.

Ashwani K. Singal, MD, MS, a professor of medicine at the University of South Dakota, Vermillion, who was not involved in the study, noted that it was based on comparing a cross section of a population instead of following the participants over time.

“So, I think it’s an association rather than a cause and effect,” he said in an interview.

The authors don’t report a multivariate analysis to determine whether comorbidities or other characteristics of the patients could explain the association, he pointed out, noting that obesity, for example, can increase the risk for both NAFLD and sleep apnea.

Still, Dr. Singal said, the paper will influence him to mention sleep in the context of lifestyle factors that can affect fatty liver disease. “I’m going to tell my patients, and tell the community physicians to tell their patients, to follow a good sleep hygiene and make sure that they sleep at least 5-7 hours.”

Dr. Singal and the study authors all reported no relevant financial relationships. The study was supported by the National Research Foundation of Korea.

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

A new prognostic score is more accurate than the commonly used Model for End-Stage Liver Disease (MELD) in predicting post–transjugular intrahepatic portosystemic shunt (TIPS) survival, researchers say.

The Freiburg Index of Post-TIPS Survival (FIPS) could help patients and doctors weigh the benefits and risks of the procedure, said Chongtu Yang, MD, a postgraduate fellow at the Huazhong University of Science and Technology, Wuhan, China.

“For patients defined as high risk, the TIPS procedure may not be the optimal choice, and transplantation may be better,” Dr. Yang told this news organization. He cautioned that FIPS needs further validation before being applied in clinical practice.

The study by Dr. Yang and his colleagues was published online Feb. 9 in the American Journal of Roentgenology. To their knowledge, this is the first study to validate FIPS in a cohort of Asian patients.

Decompensated cirrhosis can cause variceal bleeding and refractory ascites and may be life threatening. TIPS can manage these complications but comes with its own risks.

To determine which patients can best benefit from the procedure, researchers have proposed a variety of prognostic scoring systems. Some were developed for other purposes, such as predicting survival following hospitalization, rather than specifically for TIPS. Additionally, few studies have compared these approaches to each other.
 

A four-way comparison

To fill that gap, Dr. Yang and his colleagues compared four predictive models: the MELD, the sodium MELD (MELD-Na), the Chronic Liver Failure–Consortium Acute Decompensation (CLIF-CAD), and FIPS.

The MELD score uses serum bilirubin, serum creatinine, and the international normalized ratio (INR) of prothrombin time. MELD-Na adds sodium to this algorithm. The CLIF-CAD score is calculated using age, serum creatinine, INR, white blood count, and sodium level. FIPS, which was recently devised to predict results with TIPS, uses age, bilirubin, albumin, and creatinine.

To see which yielded more accurate predictions, Dr. Yang and his colleagues followed 383 patients with cirrhosis (mean age, 55 years; 341 with variceal bleeding and 42 with refractory ascites) who underwent TIPS placement at Wuhan Union Hospital between January 2016 and August 2021.

The most common cause of cirrhosis was hepatitis B infection (58.2% of patients), followed by hepatitis C infection (11.7%) and alcohol use (13.6%).

The researchers followed the patients for a median of 23.4 months. They lost track of 31 patients over that time, and another 72 died. The survival rate after TIPS placement was 92.3% at 6 months, 87.8% at 12 months, and 81.2% at 24 months. Thirty-seven patients received a TIPS revision.

In their first measure of the models’ accuracy, the researchers used a concordance index, which compares actual results with predicted results. The number of concordant pairs are divided by the total number of possible evaluation pairs. A score of 1 represents 100% accuracy.

By this measure, the prediction of survival at 6 months was highest for FIPS followed by CLIF-CAD, MELD, and MELD-Na. However, the confidence intervals overlapped.

Is FIPS worth implementing?

With scores this close, it may not be worth changing the predictive model clinicians use for choosing TIPS candidates, said Nancy Reau, MD, chief of hepatology at Rush University Medical Center, Chicago, who was not involved in the study.

MELD scores are already programmed into many electronic medical record systems in the United States, and clinicians are familiar with using that system to aid in further decisions, such as decisions regarding other kinds of surgery, she told this news organization.

“If you’re going to try to advocate for a new system, you really have to show that the performance of the predictive score is monumentally better than the tried and true,” she said.

Dr. Yang and Dr. Reau report no relevant financial relationships.

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

A new prognostic score is more accurate than the commonly used Model for End-Stage Liver Disease (MELD) in predicting post–transjugular intrahepatic portosystemic shunt (TIPS) survival, researchers say.

The Freiburg Index of Post-TIPS Survival (FIPS) could help patients and doctors weigh the benefits and risks of the procedure, said Chongtu Yang, MD, a postgraduate fellow at the Huazhong University of Science and Technology, Wuhan, China.

“For patients defined as high risk, the TIPS procedure may not be the optimal choice, and transplantation may be better,” Dr. Yang told this news organization. He cautioned that FIPS needs further validation before being applied in clinical practice.

The study by Dr. Yang and his colleagues was published online Feb. 9 in the American Journal of Roentgenology. To their knowledge, this is the first study to validate FIPS in a cohort of Asian patients.

Decompensated cirrhosis can cause variceal bleeding and refractory ascites and may be life threatening. TIPS can manage these complications but comes with its own risks.

To determine which patients can best benefit from the procedure, researchers have proposed a variety of prognostic scoring systems. Some were developed for other purposes, such as predicting survival following hospitalization, rather than specifically for TIPS. Additionally, few studies have compared these approaches to each other.
 

A four-way comparison

To fill that gap, Dr. Yang and his colleagues compared four predictive models: the MELD, the sodium MELD (MELD-Na), the Chronic Liver Failure–Consortium Acute Decompensation (CLIF-CAD), and FIPS.

The MELD score uses serum bilirubin, serum creatinine, and the international normalized ratio (INR) of prothrombin time. MELD-Na adds sodium to this algorithm. The CLIF-CAD score is calculated using age, serum creatinine, INR, white blood count, and sodium level. FIPS, which was recently devised to predict results with TIPS, uses age, bilirubin, albumin, and creatinine.

To see which yielded more accurate predictions, Dr. Yang and his colleagues followed 383 patients with cirrhosis (mean age, 55 years; 341 with variceal bleeding and 42 with refractory ascites) who underwent TIPS placement at Wuhan Union Hospital between January 2016 and August 2021.

The most common cause of cirrhosis was hepatitis B infection (58.2% of patients), followed by hepatitis C infection (11.7%) and alcohol use (13.6%).

The researchers followed the patients for a median of 23.4 months. They lost track of 31 patients over that time, and another 72 died. The survival rate after TIPS placement was 92.3% at 6 months, 87.8% at 12 months, and 81.2% at 24 months. Thirty-seven patients received a TIPS revision.

In their first measure of the models’ accuracy, the researchers used a concordance index, which compares actual results with predicted results. The number of concordant pairs are divided by the total number of possible evaluation pairs. A score of 1 represents 100% accuracy.

By this measure, the prediction of survival at 6 months was highest for FIPS followed by CLIF-CAD, MELD, and MELD-Na. However, the confidence intervals overlapped.

Is FIPS worth implementing?

With scores this close, it may not be worth changing the predictive model clinicians use for choosing TIPS candidates, said Nancy Reau, MD, chief of hepatology at Rush University Medical Center, Chicago, who was not involved in the study.

MELD scores are already programmed into many electronic medical record systems in the United States, and clinicians are familiar with using that system to aid in further decisions, such as decisions regarding other kinds of surgery, she told this news organization.

“If you’re going to try to advocate for a new system, you really have to show that the performance of the predictive score is monumentally better than the tried and true,” she said.

Dr. Yang and Dr. Reau report no relevant financial relationships.

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

A new prognostic score is more accurate than the commonly used Model for End-Stage Liver Disease (MELD) in predicting post–transjugular intrahepatic portosystemic shunt (TIPS) survival, researchers say.

The Freiburg Index of Post-TIPS Survival (FIPS) could help patients and doctors weigh the benefits and risks of the procedure, said Chongtu Yang, MD, a postgraduate fellow at the Huazhong University of Science and Technology, Wuhan, China.

“For patients defined as high risk, the TIPS procedure may not be the optimal choice, and transplantation may be better,” Dr. Yang told this news organization. He cautioned that FIPS needs further validation before being applied in clinical practice.

The study by Dr. Yang and his colleagues was published online Feb. 9 in the American Journal of Roentgenology. To their knowledge, this is the first study to validate FIPS in a cohort of Asian patients.

Decompensated cirrhosis can cause variceal bleeding and refractory ascites and may be life threatening. TIPS can manage these complications but comes with its own risks.

To determine which patients can best benefit from the procedure, researchers have proposed a variety of prognostic scoring systems. Some were developed for other purposes, such as predicting survival following hospitalization, rather than specifically for TIPS. Additionally, few studies have compared these approaches to each other.
 

A four-way comparison

To fill that gap, Dr. Yang and his colleagues compared four predictive models: the MELD, the sodium MELD (MELD-Na), the Chronic Liver Failure–Consortium Acute Decompensation (CLIF-CAD), and FIPS.

The MELD score uses serum bilirubin, serum creatinine, and the international normalized ratio (INR) of prothrombin time. MELD-Na adds sodium to this algorithm. The CLIF-CAD score is calculated using age, serum creatinine, INR, white blood count, and sodium level. FIPS, which was recently devised to predict results with TIPS, uses age, bilirubin, albumin, and creatinine.

To see which yielded more accurate predictions, Dr. Yang and his colleagues followed 383 patients with cirrhosis (mean age, 55 years; 341 with variceal bleeding and 42 with refractory ascites) who underwent TIPS placement at Wuhan Union Hospital between January 2016 and August 2021.

The most common cause of cirrhosis was hepatitis B infection (58.2% of patients), followed by hepatitis C infection (11.7%) and alcohol use (13.6%).

The researchers followed the patients for a median of 23.4 months. They lost track of 31 patients over that time, and another 72 died. The survival rate after TIPS placement was 92.3% at 6 months, 87.8% at 12 months, and 81.2% at 24 months. Thirty-seven patients received a TIPS revision.

In their first measure of the models’ accuracy, the researchers used a concordance index, which compares actual results with predicted results. The number of concordant pairs are divided by the total number of possible evaluation pairs. A score of 1 represents 100% accuracy.

By this measure, the prediction of survival at 6 months was highest for FIPS followed by CLIF-CAD, MELD, and MELD-Na. However, the confidence intervals overlapped.

Is FIPS worth implementing?

With scores this close, it may not be worth changing the predictive model clinicians use for choosing TIPS candidates, said Nancy Reau, MD, chief of hepatology at Rush University Medical Center, Chicago, who was not involved in the study.

MELD scores are already programmed into many electronic medical record systems in the United States, and clinicians are familiar with using that system to aid in further decisions, such as decisions regarding other kinds of surgery, she told this news organization.

“If you’re going to try to advocate for a new system, you really have to show that the performance of the predictive score is monumentally better than the tried and true,” she said.

Dr. Yang and Dr. Reau report no relevant financial relationships.

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

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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

A new scoring system proved more accurate than several other available models at predicting the 30-day mortality risk for patients with alcohol-associated hepatitis (AH), according to new data.

The system, called the Mortality Index for Alcohol-Associated Hepatitis (MIAAH), was created by a team of Mayo Clinic researchers, who published their results in Mayo Clinic Proceedings.

Among the currently available prognostic models for assessing AH severity are the Model for End-Stage Liver Disease (MELD); the Age, serum Bilirubin, International normalized ratio, and serum Creatinine (ABIC) score; the Maddrey Discriminant Function (MDF); and the Glasgow Alcoholic Hepatitis Score (GAHS). However, these models have poor accuracy, with the area under the curve between 0.71 and 0.77.

By comparison, the new model has an accuracy of 86% in predicting 30-day mortality for AH, said coauthor Ashwani K. Singal, MD, MS, professor of medicine at the University of South Dakota Sanford School of Medicine, Sioux Falls.

“It’s a better predictor of the outcome, and that’s what sets it apart,” he told this news organization. “I think providers and patients will benefit.”

He said accuracy in determining the likelihood of death can help clinicians better determine treatment options and prepare patients and their families.

Camille Kezer, MD, a Mayo Clinic resident internist and first author of the paper, said in a statement, “MIAAH also has the advantage of performing well in patients, regardless of whether they’ve been treated with steroids, which makes it generalizable.”
 

Creating and validating the MIAAH

Researchers analyzed the health records of 266 eligible patients diagnosed with AH between 1998 and 2018 at the Mayo Clinic, Rochester, Minn. The patients collectively had a 30-day mortality rate of 19.2%.

They then studied the effect of several variables, of which the following were found to be significantly associated with mortality: age (P = .002), blood urea nitrogen (P = .003), albumin (P = .01), bilirubin (P = .02), and international normalized ratio (P = .001).

Mayo researchers built the MIAAH model using these variables and found that it was able to achieve a C statistic of 0.86, which translates into its being able to accurately predict mortality more than 86% of the time. When tested in the initial cohort of 266 patients, MIAAH had a significantly superior C statistic compared with several other available models, such as the MELD, MDF, and GAHS, although not for the ABIC.

The researchers then tested the MIAAH model in a validation cohort of 249 patients from health care centers at the University of South Dakota, Sioux Falls, and the University of Kansas, Lawrence. In this cohort, the MIAAH’s C statistic decreased to 0.73, which remained significantly more accurate than the MDF but was comparable to that found with the MELD.
 

Helping with transplant decisions

There are no pharmacologic treatments that can reduce 90-day mortality in severe cases of AH, and only a small survival benefit at 30 days has been reported with prednisolone use.

With a shortage of liver donors, many centers still require 6 months of alcohol abstinence for transplant consideration, although exceptions are sometimes made for cases of early transplant.

A model that more accurately predicts who is at the highest risk of dying within a month can help clinicians decide how best to proceed, Dr. Singal said.

Paul Martin, MD, chief of the division of digestive health and liver diseases, Mandel Chair in gastroenterology, and professor of medicine at the University of Miami, told this news organization that the model is potentially important in light of the rising prevalence of AH.

“The numbers of patients with AH are unequivocally increasing and often in young patients,” he noted, presenting difficult choices of who to treat with steroids and who to refer for a transplant.

“This model is certainly timely,” he said. “We need more accuracy in predicting which patients will recover with medical therapy and which patients won’t in the absence of a liver transplant.”

He noted, however, that the study’s retrospective design requires that it’s validated prospectively: “not only looking at the outcome in terms of mortality of patients, but its potential utility in identifying candidates for liver transplantation who are not going to recover on their own.”

He said it was unlikely that the model would replace others, particularly MELD, which is ingrained in practices in the United States and other countries, but may instead have a complementary role.

Dr. Singal, Dr. Kezer, and Dr. Martin report no relevant financial relationships.

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