Hepatology

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

Seladelpar, an investigational selective agonist of peroxisome proliferator–activated receptor-delta (PPAR-delta), significantly improves liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with primary biliary cholangitis (PBC), according to the full results of the RESPONSE phase 3 study.

“At a dose of 10 mg daily, 1 in 4 patients normalize their alkaline phosphatase level,” chief investigator Gideon Hirschfield, PhD, BM BChir, with the Toronto Center for Liver Disease at Toronto General Hospital, Toronto, Ontario, Canada, said in an interview.

‘Unequivocal’ Progress

Up to 40% of patients with PBC have an inadequate response to first-line therapy with ursodeoxycholic acid (UDCA) and are at a high risk for disease progression. More than half of patients with the disease fail to respond to second-line therapy with obeticholic acid.

Seladelpar, and the dual PPAR-alpha and PPAR-delta agonist elafibranor, are an “unequivocal sign of progress, marking the arrival of a new era in which PBC treatment is expected to provide both biochemical benefits and amelioration of symptoms for patients,” David N. Assis, MD, with the Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, wrote in a linked editorial.

Significant Reduction in Pruritus

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the seladelpar group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score of 4 or higher out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with seladelpar than with placebo (change from baseline, −3.2 points vs −1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate to severe pruritus population and the overall population also favored seladelpar over placebo for itch relief, which had a positive impact on sleep. Similar results demonstrating reductions in itch and improvements in sleep were observed using the PBC-40 questionnaire.

Adverse events that led to discontinuation of seladelpar or placebo were rare, and there was no between-group difference in the incidence of serious adverse events.

“No worrisome adverse events affecting the muscles were observed, including among patients receiving statins. Certain gastrointestinal events — abdominal pain, abdominal distention, and nausea — were reported more frequently in the seladelpar group than in the placebo group,” the study authors wrote.

The most common adverse events that occurred in ≥ 5% of patients in either group were COVID-19 and pruritus. A greater percentage of patients treated with placebo reported pruritus (15.4% vs 4.7%) as an adverse event — a finding consistent with the positive effect of seladelpar on reducing pruritus.

The researchers noted that 96.4% of patients who participated in the RESPONSE trial chose to enroll in the extension trial to evaluate long-term safety and the side-effect profile of seladelpar.
 

Potential First-Line Treatment?

In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”

“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.

“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.

Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.

“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.

Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.

The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Augmenting an intake of vitamin E, via both diet and supplements, may help prevent metabolic dysfunction–associated steatotic liver disease (MASLD), particularly in adults without hyperlipidemia, new data showed.

METHODOLOGY:

• MASLD (formerly known as nonalcoholic fatty liver disease) is a common chronic liver disease, and its severe form — metabolic dysfunction–associated steatohepatitis (formerly nonalcoholic steatohepatitis) — is associated with oxidative stress. As an antioxidant, vitamin E may protect against MASLD.
• Researchers analyzed data for 6122 adults from the National Health and Nutrition Examination Survey from 2017 to 2020.
• Information on dietary, supplementary, and total vitamin E intake was obtained from two 24-hour dietary recall interviews.
• The extent of hepatic steatosis was measured by liver ultrasound transient elastography, with MASLD defined as a controlled attenuated parameter threshold of ≥ 288 dB/m.

TAKEAWAY:

• After adjustment for sociodemographic characteristics, adults with MASLD had lower dietary and total intake of vitamin E, and dietary and total vitamin E intake was inversely associated with MASLD outcome.
• Adults in the top quartile of dietary vitamin E intake had approximately 40% lower odds of MASLD (odds ratio [OR], 0.60; P = .0091).
• Vitamin E supplement use was associated with 34% reduced odds of MASLD (OR, 0.66; P = .0249), whereas adults in the top quartile of total vitamin E intake had a 33% lower likelihood of MASLD (OR, 0.67; P = .0538).
• The findings were robust to sensitivity analysis, and the effects were stronger in those without hyperlipidemia.

IN PRACTICE:

“Increasing dietary sources of vitamin E is beneficial for preventing [MASLD], particularly in individuals without hyperlipidemia,” the researchers concluded.

SOURCE:

The study, with first author Xiangjun Qi, Guangzhou University of Chinese Medicine, Guangzhou, China, was published online in Scientific Reports.

LIMITATIONS:

Causality cannot be determined due to the cross-sectional study design. Dietary recalls may not fully reflect the dietary status of participants, which may influence assessment of exposure to some extent.

DISCLOSURES:

The study had no specific funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with steatotic liver disease (SLD) related to alcohol consumption are at greater risk of mortality than men with the same condition, new research suggested.

METHODOLOGY:

• Researchers analyzed data from the US National Health and Nutrition Examination Survey III (NHANES III, 1988-1994), which included standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake.
• Among 10,007 participants aged 20 years and older (mean age, 42 years; 50.3% men) who were included and followed for a median of 26.7 years, 1461 had metabolic dysfunction–associated steatotic liver disease (MASLD), 105 alcohol-related liver disease (ALD), 225 metabolic dysfunction-associated and alcohol-related liver disease (MetALD), 180 other types of SLD, and 8036 no SLD.
• Researchers examined SLD-associated risks for all-cause mortality after adjustment for baseline age, smoking status, systolic blood pressure, antihypertensives, type 2 diabetes, diabetic medication use, body mass index, total cholesterol, high-density lipoprotein cholesterol, lipid-lowering therapy, race, and family income.

TAKEAWAY:

• In men, the prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, whereas the corresponding prevalence among women was 10.3%, 1.2%, and 0.3%, respectively.
• In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex compared with those without SLD.
• In contrast, MetALD was associated with an 83% higher hazard of all-cause mortality in women (hazard ratio [HR], 1.83), but not significantly associated with mortality in men.
• ALD was significantly associated with all-cause mortality in both sexes, with a greater magnitude in women than men (HRs, 3.49 vs 1.89, respectively) — the equivalent of about a 160% higher mortality risk for women.
• With regard to SLD severity, the trend across worsening phenotypes (ie, MASLD, MetALD, or ALD) was significant for sex differences in mortality but not in prevalence.

IN PRACTICE:

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” the authors wrote.

SOURCE:

The study, led by Hongwei Ji of Qingdao University, Qingdao, Shandong, China, and Susan Cheng, MD, Cedars-Sinai Medical Center, Los Angeles, was published in the February issue of Journal of Hepatology.

LIMITATIONS:

The study data came from NHANES III, which was conducted between 1988 and 1994. This is a potential limitation, as the prevalence of metabolic dysfunction and alcohol use may have changed since then.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China, the Taishan Scholar Program of Shandong Province, the Shandong Provincial Natural Science Foundation, the National Institutes of Health, and the NIH National Center for Advancing Translational Sciences UCLA Clinical and Translational Research Center. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Cognitive impairment in some US veterans may be due to treatable hepatic encephalopathy (HE) rather than dementia, new research suggested.

From 5%-10% of veterans diagnosed with dementia had possible undiagnosed cirrhosis, implicating HE as a contributor to cognitive impairment, found the study by Jasmohan S. Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Virginia, and colleagues.

The research was prompted, in part, by an earlier case study by Dr. Bajaj and colleagues that showed that two older men diagnosed with dementia and Parkinson’s disease actually had HE, meaning their symptoms were due to advanced but treatable liver disease.

“Once they were properly diagnosed, whatever had been considered dementia was gone,” Dr. Bajaj said. “The spouse of one man said, ‘My husband is a different person now.’ It’s not that clinicians don’t know how to treat HE; the problem was that they did not suspect it.”

Among veterans with cirrhosis, concomitant dementia is common and is difficult to distinguish from HE, but the extent to which patients with dementia also have undiagnosed cirrhosis and HE is unknown, the authors of the current study wrote. “Undiagnosed cirrhosis among veterans with dementia could raise the possibility that part of their cognitive impairment may be due to reversible HE,” they added.

To investigate, the researchers examined the prevalence and risk factors of undiagnosed cirrhosis — and therefore, possible HE — among US veterans.

The study was published online in JAMA Network Open.
 

Dementia or Cirrhosis?

Using the VHA Corporate Data Warehouse, researchers analyzed medical records of 177,422 US veterans diagnosed with dementia but not cirrhosis between 2009 and 2019 and with sufficient laboratory test results to calculate their Fibrosis-4 (FIB-4) scores. The mean age was 78.35 years, 97.1% were men, and 80.7% were White individuals.

The FIB-4 score for each patient was calculated using the most recent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels or values and platelet values that were closest to the index date during the two years after the index dementia date.

Age is in the numerator of the FIB-4 score calculation; hence, higher age could lead to an erroneously high FIB-4 score, the authors noted. Therefore, for patients older than 65 years, the researchers entered 65 years as an input variable, rather than the actual age.

A FIB-4 score > 2.67 was suggestive of advanced fibrosis, whereas a score > 3.25 was suggestive of cirrhosis. 

A total of 18,390 (10.3%) veterans had a FIB-4 score > 2.67, and 9373 (5.3%) had a FIB-4 score > 3.25.

In multivariable logistic regression models, a FIB-4 score > 3.25 was associated with older age (odds ratio [OR], 1.07), male sex (OR, 1.43), congestive heart failure (OR, 1.48), viral hepatitis (OR, 1.79), an Alcohol Use Disorders Identification Test score showing problem drinking (OR, 1.56), and chronic kidney disease (OR, 1.11).

In contrast, a FIB-4 score > 3.25 was inversely associated with the White race (OR, 0.79), diabetes (OR, 0.78), hyperlipidemia (OR, 0.84), stroke (OR, 0.85), tobacco use disorder (OR, 0.78), and rural residence (OR, 0.92).

Similar findings were associated with the FIB-4 greater than 2.67 threshold.

In a follow-up validation study among 89 veterans diagnosed with dementia at a single center, the researchers found similar results: 4.4%-11.2% of participants had high FIB-4 scores, suggestive of HE.

After investigating further, they concluded that 5% of patients in that cohort had reasons other than cirrhosis for their high FIB-4 scores. The remaining patients (95%) had evidence of cirrhosis, had risk factors, and/or had no other explanation for their high FIB-4 scores.

“The combination of high FIB-4 scores and other risk factors for liver disease in patients with dementia raises the possibility that reversible HE could be a factor associated with cognitive impairment,” the authors wrote. “These findings highlight the potential to enhance cognitive function and quality of life by increasing awareness of risk factors and diagnostic indicators of advanced liver disease that may be associated with HE as a factor or as a differential diagnosis of dementia among clinicians other than liver specialists.”
 

FIB-4 Screening Advised

“An elderly patient with cirrhosis used to be an oxymoron, because we never used to have people who lived this long or were diagnosed this late with cirrhosis,” Dr. Bajaj told this news organization. “It’s a good problem to have because people are now living longer, but it also means that we need to have every single person who is taking care of patients with what is deemed to be dementia know that the patient could also have an element of encephalopathy.”

Increased awareness is important because, unlike dementia, encephalopathy is very easily treated, Dr. Bajaj said. “The biggest, easiest, correctable cause is to figure out if they have severe liver disease, and if that’s the case, your friendly neighborhood gastroenterologist is waiting for you,” he added.

The finding that cirrhosis was present in 95% of patients in the validation cohort is “very impressive, as they had excluded from the consideration all those with obvious cirrhosis before the FIB-4 was done,” said William Carey, MD, acting hepatology section head in the Department of Gastroenterology, Hepatology and Nutrition at Cleveland Clinic’s Digestive Disease Institute in Ohio. “This validates FIB-4 as a powerful tool for cirrhosis case-finding.” 

Ordering a FIB-4 “is within the skill set of every healthcare provider,” Dr. Carey, who was not involved in the study, told this news organization. “Patients with altered mental status, including suspected or proven dementia, should be screened for possible cirrhosis, as future management will change. Those with elevated FIB-4 results should also be tested for possible HE and treated if it is present.”

The study was partly funded by VA Merit Review grants to Dr. Bajaj. Dr. Bajaj reported receiving grants from Bausch, Grifols, Sequana, and Mallinckrodt outside the submitted work. Dr. Carey reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Pretreatment testing of patients starting systemic immunomodulatory therapies for chronic skin diseases fell short of recommendations, based on an analysis of more than 120,000 individuals in a national commercial insurance claims database.

Because of concerns for the potential reactivation of tuberculosis or hepatitis B or C, or for an increased risk for infections, myelosuppression, and hepatoxicity in the wake of immunomodulator use, some medical societies recommend screening patients for hepatitis B, hepatitis C, and tuberculosis before starting these medications, wrote Maria C. Schneeweiss, MD, of Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues.

“Conducting this study was crucial because of the increasing use of systemic immunomodulatory agents for chronic inflammatory skin diseases and the recognized need for pretreatment testing to prevent complications,” coauthor Denys Shay, a PhD candidate in population health sciences at Harvard University, Cambridge, Massachusetts, said in an interview.

“Despite recommendations from professional societies, there was a lack of clarity on how consistently these guidelines were being followed in the United States. This study aimed to fill that gap in knowledge, providing a comprehensive view of current practices and highlighting areas for improvement,” he said.

In the study, published online in JAMA Dermatology, he and his coauthors identified 122,308 adults in the United States with psoriasis, hidradenitis suppurativa, or atopic dermatitis who started an immunomodulatory agent, including methotrexate (28,684 patients), tumor necrosis factor (TNF)–alpha inhibitors (40,965), ustekinumab (12,841), interleukin (IL)-23 inhibitors (6116), IL-17A inhibitors (9799), dupilumab (7787), and apremilast (16,116). The data were from a commercial insurance claims database from December 31, 2002, to December 31, 2020.

The primary outcome was the proportion of patients who underwent recommended screening lab tests including tuberculosis, hepatitis, liver function, complete blood cell counts (CBCs), and lipid panels within 6 months before treatment initiation and during the first 2 years of treatment. The median age of the study population was 49 years, and 52.1% were male.

A CBC was the most common pretreatment test across treatments, performed in 41%-69% of patients before starting treatment. Tuberculosis screening occurred in 11%-59% of patients within 6 months of initiating treatment, and 3%-26% had updated tests after 1 year. Similarly, 13%-41% of patients underwent hepatitis screening prior to treatment.

The highest levels of pretreatment testing occurred for TNF-alpha inhibitors, ustekinumab, IL-17A inhibitors, and IL-23 inhibitors, with similar patterns, while the lowest levels of testing occurred with apremilast and dupilumab.

Testing prevalence before starting apremilast and after a year of treatment was 15%-45% and 9%-36%, respectively. Testing before initiation and a year into treatment with dupilumab was 11%-41% and 3%-25%, respectively.

The findings were limited by several factors including the descriptive design, which does not allow for evaluation of the testing practices, the researchers said.

However, the results show the extent of patients with chronic inflammatory skin diseases (CISDs) who do not undergo pretreatment testing, and research is needed to create testing practices on the basis of recommendations for each agent and incorporating each patient’s history and clinical profile, they concluded.

“The finding that less than 60% of patients received recommended pretreatment testing was initially somewhat surprising,” Shay said in the interview. “However, the context provided by higher rates of baseline testing within the 6-12 months before treatment initiation and the potential for additional testing not captured by the dataset — such as hospital stays — suggests that the gap may not be as large as this estimate,” he said.

“The key message for clinicians is that there are considerable variations in laboratory testing practices with regard to the initiation of systemic immunomodulatory agents in patients with CISDs,” Shay said. “This represents a divergence from existing testing guidelines.”

“Further research is needed to understand the reasons for the variations in pretreatment testing practices and whether this heterogeneity affects patient outcomes,” he added.

Resist Routine Testing

The study findings represent a call to action in the form of ongoing assessment of the safety, clinical utility, and cost-effectiveness of pretreatment testing, wrote Clinton W. Enos, MD, Ana Ormaza Vera, MD, and Abby S. Van Voorhees, MD, of the Department of Dermatology, Eastern Virginia Medical School, Norfolk, Virginia, in an accompanying editorial.

The data in the current study suggesting less frequent laboratory testing compared with current guidelines could stem from a high comfort level with many of the therapies that have been available and in use for many years, they noted. Clinicians’ lack of knowledge of the laboratory screening and monitoring guidelines also may play a role, they said.

However, the authors cautioned against routine checking of laboratory results “without purpose” and without attention to their clinical utility and cost. “A thorough medical history is essential and can serve as a sensitive indicator of which patients are more at risk for diseases such as TB or hepatitis, thereby allowing for more meaningful laboratory screening use,” they said.

Evidence supporting prescreening labs for the spectrum of systemic agents used in dermatology varies considerably, “some trapped in time and carried forward for decades until finally questioned, others rooted in treatment mechanism and clinical data,” Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, said in an interview.

The study elucidated the current state of clinical practice, said Friedman, who was not involved with the study. This includes screening even if the label says it is not necessary and letting screening slide when guidelines say otherwise — even if the guidelines are outdated and insurance requires certain metrics prior to approval, he said.

Looking ahead, “we need better consensus and even better communication/education on said guidance,” Dr. Friedman said. “Clear, concise, evidenced-based, and expert-validated guidance to ensure we are meaningfully using medical resources” is what is needed, he added. “It will certainly take a village, and close collaboration between the industry and practitioners is key to success.”

The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Shay had no financial conflicts to disclose. Lead author Dr. Schneeweiss disclosed grants from UCB Pharma and AbbVie to Brigham and Women’s Hospital outside the submitted work. Other authors disclosed receiving personal fees from Aetion and grants from UCB Pharma and Takeda outside the submitted work; grants from Amarin, Kowa, Novartis, and Pfizer outside the submitted work; and personal fees from Hims & Hers, AbbVie, Sun Pharmaceuticals, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, ACOM, Olaplex, and Legacy Healthcare during the study. No other disclosures were reported.

Editorial author Dr. Enos disclosed serving as an investigator for Amgen and Castle Biosciences and receiving grants from Arcutis Biotherapeutics outside the submitted work. Dr. Van Voorhees disclosed an honorarium outside the submitted work.

Dr. Friedman had no relevant financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

The oral thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in both 80-mg and 100-mg doses was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis, according to the results of the ongoing phase 3 MAESTRO-NASH trial published in The New England Journal of Medicine.

Although certain findings from this trial were initially presented at the European Association for the Study of the Liver Congress 2023, the publication of the full peer-reviewed paper represents a potentially significant milestone in the management of NASH, a disease for which there is currently no approved pharmacologic treatment. 

“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” wrote the authors, led by principal investigator Stephen Harrison, MD, chairman of Pinnacle Clinical Research and Summit Clinical Research in San Antonio, Texas. 

The trial uses the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. 
 

A Closer Look at MAESTRO-NASH

Investigators enrolled 996 participants who were randomly assigned to receive placebo or resmetirom at 80 mg or 100 mg. Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. 

They observed that patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, vs 9.7% on placebo. Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the increasing-dose groups, respectively, compared with 14.2% on placebo (P < .001 for both doses compared with placebo). 

The effects with resmetirom were consistent across key subgroups, regardless of baseline fibrosis stage; baseline NAFLD activity score; or type 2 diabetes status, age, and sex. 

“Multiple non-invasive tests for NASH, steatosis, and fibrosis (including blood biomarkers and imaging) showed a similar direction of effects favoring resmetirom treatment, which supports the findings for the primary end points,” Dr. Harrison and colleagues wrote. 

The majority of patients with NASH also have diabetes. As a result, patients with NASH are known to have a high cardiovascular risk and mortality. However, MAESTRO-NASH investigators reported that compared with those receiving placebo, patients on resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). These findings were consistent with earlier studies of resmetirom. 

From baseline to week 24, LDL cholesterol levels were reduced by -13.6% in the 80-mg and by -16.3% in the 100-mg resmetirom groups compared with 0.1% in the placebo group (P < .001).

More patients in the 100-mg group than in the 80-mg or placebo groups discontinued the trial due to adverse events (6.8% vs 1.8% and 2.2%, respectively). Diarrhea and nausea occurred more frequently in the resmetirom groups than in the placebo group. Serious adverse events occurred with similar incidences across the 100-mg, 80-mg, and placebo groups (12.7%, 10.9%, and 11.5%, respectively).

Although to date the MAESTRO-NASH trial lacks clinical outcomes, over its planned duration of 54 months, investigators will accrue data on liver-related outcomes, including progression to cirrhosis. Likewise, long-term safety data will become available with the trial’s completion. 

Disclosure forms provided by the authors are available with the full text of the NEJM paper at NEJM.org. 

A version of this article appeared on Medscape.com.

To curb alcohol-associated liver disease (ALD), alcohol consumption should be avoided among those with underlying obesity, chronic hepatitis C infection, hepatitis B virus infection, or a history of gastric bypass, according to a new clinical guideline from the American College of Gastroenterology.

In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.

Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.

“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”

The guideline was published in the January issue of the American Journal of Gastroenterology.
 

Updating ALD Recommendations

With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.

In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.

To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.

Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.

“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”

In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.

Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.

“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
 

Policy Implications

Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.

“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”

Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.

“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.

Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.

“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”

The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.

A version of this article appeared on Medscape.com.

To curb alcohol-associated liver disease (ALD), alcohol consumption should be avoided among those with underlying obesity, chronic hepatitis C infection, hepatitis B virus infection, or a history of gastric bypass, according to a new clinical guideline from the American College of Gastroenterology.

In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.

Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.

“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”

The guideline was published in the January issue of the American Journal of Gastroenterology.
 

Updating ALD Recommendations

With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.

In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.

To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.

Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.

“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”

In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.

Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.

“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
 

Policy Implications

Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.

“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”

Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.

“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.

Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.

“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”

The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.

A version of this article appeared on Medscape.com.

To curb alcohol-associated liver disease (ALD), alcohol consumption should be avoided among those with underlying obesity, chronic hepatitis C infection, hepatitis B virus infection, or a history of gastric bypass, according to a new clinical guideline from the American College of Gastroenterology.

In addition, health systems need to overcome barriers to treating alcohol use disorder (AUD) and commit to creating a multidisciplinary care model with behavioral interventions and pharmacotherapy for patients.

Experts were convened to develop these guidelines because it was “imperative to provide an up-to-date, evidence-based blueprint for how to care for patients, as well as guide prevention and research efforts in the field of ALD for the coming years,” said the first author, Loretta Jophlin, MD, PhD, assistant professor of medicine in gastroenterology, hepatology, and nutrition and medical director of liver transplantation at the University of Louisville in Kentucky.

“In recent years, perhaps fueled by the COVID-19 pandemic, alcohol use has been normalized in an increasing number of situations,” she said. “Drinking was normalized as a coping mechanism to deal with many of the sorrows we experienced during the pandemic, including loss of purposeful work and social isolation, and many more people are struggling with AUD. So many aspects of our culture have been inundated by the presence of alcohol use, and we need to work hard to denormalize this, first focusing on at-risk populations.”

The guideline was published in the January issue of the American Journal of Gastroenterology.
 

Updating ALD Recommendations

With ALD as the most common cause of advanced hepatic disease and a frequent indicator of eventual liver transplantation, the rising incidence of alcohol use during the past decade has led to rapid growth in ALD-related healthcare burdens, the guideline authors wrote.

In particular, those with ALD tend to present at an advanced stage and progress faster, which can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. This can include alcohol-associated hepatitis (AH), which often presents with a rapid onset or worsening of jaundice and can lead to acute or chronic liver failure.

To update the guideline, Dr. Jophlin and colleagues analyzed data based on a patient-intervention-comparison-outcome format, resulting in 34 key concepts or statements and 21 recommendations.

Among them, the authors recommended screening and treating AUD with the goal of helping patients who have not yet developed significant liver injury and preventing progression to advanced stages of ALD, particularly among at-risk groups who have had an increasing prevalence of severe AUD, including women, younger people, and Hispanic and American Indian patients.

“So many patients are still told to ‘stop drinking’ or ‘cut back’ but are provided no additional resources. Without offering referrals to treatment programs or pharmacologic therapies to assist in abstinence, many patients are not successful,” Dr. Jophlin said. “We hope these guidelines empower providers to consider selected [Food and Drug Administration]-approved medications, well-studied off-label therapies, and nonpharmacologic interventions to aid their patients’ journeys to abstinence and hopefully avert the progression of ALD.”

In addition, the guidelines provide recommendations for AH treatment. In patients with severe AH, the authors offered strong recommendations against the use of pentoxifylline and prophylactic antibiotics, and in support of corticosteroid therapy and intravenous N-acetyl cysteine as an adjuvant to corticosteroids.

Liver transplantation, which may be recommended for carefully selected patients, is being performed at many centers but remains relatively controversial, Dr. Jophlin said.

“Questions remain about ideal patient selection as center practices vary considerably, yet we have started to realize the impacts of relapse after transplantation,” she said. “The guidelines highlight the knowns and unknowns in this area and will hopefully serve as a catalyst for the dissemination of centers’ experiences and the development of a universal set of ethically sound, evidence-based guidelines to be used by all transplant centers.”
 

Policy Implications

Dr. Jophlin and colleagues noted the importance of policy aimed at alcohol use reduction, multidisciplinary care for AUD and ALD, and additional research around severe AH.

“As a practicing transplant hepatologist and medical director of a liver transplant program in the heart of Bourbon country, I am a part of just one healthcare team experiencing ALD, particularly AH, as a mass casualty event. Healthcare teams are fighting an unrelenting fire that the alcohol industry is pouring gasoline on,” Dr. Jophlin said. “It is imperative that healthcare providers have a voice in the policies that shape this preventable disease. We hope these guidelines inspire practitioners to explore our influence on how alcohol is regulated, marketed, and distributed.”

Additional interventions and public policy considerations could help reduce alcohol-related morbidity and mortality at a moment when the characteristics of those who present with AUD appear to be evolving.

“The typical person I’m seeing now is not someone who has been drinking heavily for decades. Rather, it’s a young person who has been drinking heavily for many months or a couple of years,” said James Burton, MD, a professor of medicine at the University of Colorado School of Medicine and medical director of liver transplantation at the University of Colorado Hospital’s Anschutz Medical Campus in Aurora.

Dr. Burton, who wasn’t involved with the guideline, noted it’s become more common for people to drink multiple alcoholic drinks per day for multiple times per week. Patients often don’t think it’s a problem, even as he discusses their liver-related issues.

“We can’t just keep living and working the way we were 10 years ago,” he said. “We’ve got to change how we approach treatment. We have to treat liver disease and AUD.”

The guideline was supported by several National Institutes of Health grants and an American College of Gastroenterology faculty development grant. The authors declared potential competing interests with various pharmaceutical companies. Dr. Burton reported no financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.

METHODOLOGY:

• Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
• They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
• Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.

TAKEAWAY:

• During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
• After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
• In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
• No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.

IN PRACTICE:

“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”

SOURCE:

The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.

LIMITATIONS:

The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.

DISCLOSURES:

The study did not list funding. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.

METHODOLOGY:

• Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
• They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
• Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.

TAKEAWAY:

• During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
• After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
• In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
• No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.

IN PRACTICE:

“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”

SOURCE:

The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.

LIMITATIONS:

The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.

DISCLOSURES:

The study did not list funding. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Daily consumption of up to half of a standard US drink (7.4 gram/day) does not appear to increase mortality risk in adults with steatotic liver disease (SLD) who have low risk for advanced fibrosis.

METHODOLOGY:

• Researchers used data from the National Health and Nutrition Examination Survey III (1988-1994) to elucidate the dose-dependent association of alcohol use with SLD progression.
• They identified 2834 adults with confirmed SLD (51.8% male, 34.2% non-Hispanic White), including 591 (20.8%) with intermediate or high risk for advanced fibrosis, defined as a Fibrosis-4 index (FIB-4) score of 1.3 or higher.
• Multivariable Cox regression with restricted cubic spines was used to investigate nonlinear associations between alcohol use and mortality.

TAKEAWAY:

• During median follow-up of 26 years, the mortality rate per 100,000 persons was 4342 in the group with intermediate and high risk for advanced fibrosis versus 1099 in the low-risk group.
• After adjustment for demographics and metabolic variables, there was a nonlinear association between alcohol intake and mortality in the low-risk group (P = .001 for nonlinearity).
• In the low-risk group, the mortality risk threshold was < 7.4 gram/day, which equals half a 12-ounce beer or half a glass of wine. Each additional gram above this level led to a higher death rate.
• No safe alcohol limit was evident in the intermediate- and high-risk group; their mortality risk rose with any alcohol intake.

IN PRACTICE:

“Individuals with SLD should be advised to maintain regular health monitoring and lifestyle management. Recent guidelines have recommended the FIB-4 score as a first-line assessment tool given its low cost, high accuracy, and noninvasiveness,” the authors write. “In this cohort study, we proposed using the FIB-4 score to guide clinicians in advising patients with SLD who choose not to abstain completely from alcohol.”

SOURCE:

The study, with the first author Yee Hui Yeo, MD, at Cedars-Sinai Medical Center, Los Angeles, California, was published online on December 14, 2023, in JAMA Network Open.

LIMITATIONS:

The study relied on self-reported alcohol intake and lacked data on drinking patterns. All variables were only available at baseline, with no tracking of alcohol intake changes during follow-up. Individual risks may vary and require case-by-case discussion as the data are population based.

DISCLOSURES:

The study did not list funding. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.