Liver Disease

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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

Among patients with obesity and compensated cirrhosis, bariatric surgery may significantly lower the risk of developing serious liver disease complications, according to a recent study by Cleveland Clinic researchers.

Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.

The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.

 

“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.

“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”

The study was published online in Nature Medicine.

 

Significantly Reduced Risks

As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.

Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.

After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.

Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.

Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5. 

The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.

In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.

At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.

Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.

 

Potential to Fill an Unmet Need

Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.

The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.

“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.

“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”

No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.

A version of this article appeared on Medscape.com.

Among patients with obesity and compensated cirrhosis, bariatric surgery may significantly lower the risk of developing serious liver disease complications, according to a recent study by Cleveland Clinic researchers.

Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.

The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.

 

“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.

“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”

The study was published online in Nature Medicine.

 

Significantly Reduced Risks

As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.

Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.

After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.

Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.

Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5. 

The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.

In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.

At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.

Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.

 

Potential to Fill an Unmet Need

Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.

The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.

“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.

“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”

No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.

A version of this article appeared on Medscape.com.

Among patients with obesity and compensated cirrhosis, bariatric surgery may significantly lower the risk of developing serious liver disease complications, according to a recent study by Cleveland Clinic researchers.

Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.

The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.

 

“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Ohio.

“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”

The study was published online in Nature Medicine.

 

Significantly Reduced Risks

As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.

Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤ 10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.

After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, Fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.

Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.

Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5. 

The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.

In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.

At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.

Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in hemoglobin A1c levels, as well as diabetes remission for some patients.

 

Potential to Fill an Unmet Need

Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.

The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.

“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study coauthor and a transplant hepatologist at the Cleveland Clinic who specializes in MASH-related cirrhosis. She cofounded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.

“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”

No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.

A version of this article appeared on Medscape.com.

The American Gastroenterological Association (AGA) has released an updated clinical practice guideline on the prevention of hepatitis B virus reactivation (HBVr) in at-risk persons. The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.

Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.

With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.

 

“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”

Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”

 

Main Recommendations

AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.

The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.

1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).

2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.

Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.

3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.

4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.

It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.

 

Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment

The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.

In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.

 

A ‘Useful Clinical Tool’

Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”

In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.

She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.

“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.

Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.

 

The Future

According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.

Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.

The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.

AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.

The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.

A version of this article appeared on Medscape.com.

The American Gastroenterological Association (AGA) has released an updated clinical practice guideline on the prevention of hepatitis B virus reactivation (HBVr) in at-risk persons. The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.

Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.

With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.

 

“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”

Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”

 

Main Recommendations

AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.

The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.

1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).

2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.

Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.

3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.

4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.

It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.

 

Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment

The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.

In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.

 

A ‘Useful Clinical Tool’

Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”

In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.

She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.

“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.

Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.

 

The Future

According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.

Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.

The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.

AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.

The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.

A version of this article appeared on Medscape.com.

The American Gastroenterological Association (AGA) has released an updated clinical practice guideline on the prevention of hepatitis B virus reactivation (HBVr) in at-risk persons. The document was published in Gastroenterology and replaces a previous guideline on prophylaxis for immunosuppressed patients issued in 2014.

Since then, many novel classes of immunosuppressives have been approved for various conditions, and potentially immunosuppressive therapies such as transcatheter arterial chemoembolization have been recognized as relevant to potential HBVr.

With reactivation a risk after immune-modulating exposures, such as to multiple drug classes and disease states, the update provides frontline clinicians with evidence-based advice for the management of HBVr in vulnerable individuals. And while antiviral prophylaxis is recommended for many, in select cases careful clinical monitoring may suffice for risk management.

 

“The risk of HBV reactivation depends on patient-, drug-, and disease-specific factors — and so it can range from very rare to more frequent,” said guideline coauthor Tracey G. Simon, MD, MPH, a hepatologist in the division of gastroenterology at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “Not every at-risk individual needs pharmacologic treatment, but some certainly do, and this guideline was designed to try to better identify who needs treatment, based on those important drug- and virus-specific factors.”

Simon stressed the importance of creating this guideline to include many new therapies that carry varying degrees of reactivation risk. As to the strength of the evidence, she added, “for some of the questions, the panel was satisfied with the level of certainty. However, for other questions, the data are still very sparse, and so we have tried to ensure that these areas of uncertainty are highlighted clearly for providers and patients.”

 

Main Recommendations

AGA based its clinical recommendations on balancing desirable and undesirable effects, patient values and preferences, costs, and health equity considerations. It also provided a clinical decision support tool for making pharmacologic management decisions.

The panelists reviewed data on multiple immunosuppressive therapies from older agents such as anthracycline derivatives, corticosteroids, and anti–tumor necrosis factor (anti-TNF) drugs to chimeric antigen receptor T cells and recent biologics and inhibitors.

1. For individuals at high risk for HBVr, AGA recommended antiviral prophylaxis over monitoring alone. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Prophylaxis should be started before initiating medications that carry a risk for HBVr and should be continued for at least 6 months after discontinuation of risk-imposing therapy (at least 12 months for B cell–depleting agents).

2. For individuals at moderate risk for HBVr, antiviral prophylaxis was recommended over monitoring alone. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: Use antivirals with a high barrier to resistance. Patients who place a higher value on avoiding long-term antiviral therapy and its associated cost and place a lower value on avoiding the small risk of reactivation (particularly those who are hepatitis B surface antigen [HBsAg]–negative) may reasonably select active monitoring over antiviral prophylaxis.

Careful consideration should be given to the feasibility and likelihood of adherence to long-term monitoring performed at 1- to 3-month intervals and including assessment of hepatitis B viral load and alanine aminotransferase.

3. For low-risk individuals, the AGA said monitoring alone may be used. Conditional recommendation, moderate-certainty evidence.

Implementation considerations: This recommendation assumes regular and sufficient follow-up with continued monitoring. Patients who place a higher value on avoiding the small risk of reactivation (particularly those on more than one low-risk immunosuppressive) and a lower value on the burden and cost of antiviral therapy may reasonably select antiviral therapy.

4. For individuals at risk for HBVr, the guideline recommended testing for hepatitis B. Strong recommendation, moderate-certainty evidence.

Implementation considerations: Given the Centers for Disease Control and Prevention’s universal screening guidance on hepatitis B for everyone aged 18 years or older by testing for HBsAg, anti-HBs, and total anti-hepatitis B core (HBc), the guideline said that stratifying screening practices by magnitude of HBVr risk is no longer needed.

It is reasonable to test initially for serologic markers alone (at minimum for HBsAg or anti-HBc) followed by viral load testing (HBV-DNA) if HBsAg and/or anti-HBc is positive.

 

Hepatitis C Virus (HCV) Coinfection With Direct-Acting Antiviral (DAA) Treatment

The panel identified 11 studies that provided data for the computation of baseline risk for HBVr in the HCV coinfection cohort undergoing DAA therapy.

In patients who were HBsAg-positive, the pooled baseline risk for HBVr was 240 per 1000, categorizing them to be at high risk for HBVr. The panel stated it is therefore reasonable to extend antiviral prophylaxis beyond the 12-24 weeks of DAA therapy to 6-12 months after cessation of DAA therapy, tailored by clinician judgment and patient preference.

 

A ‘Useful Clinical Tool’

Commenting on the guideline but not involved in it, Saikiran Kilaru, MD, a hepatologist at NYU Langone Health in New York City, said the update is “absolutely a useful clinical tool. Since the prior guidance was published, there has been a deluge of new medications and medication classes. Prior to the guidance, I was making recommendations based on the limited data available for hepatitis B reactivation risk for these new medications, using the 1%-10% moderate-risk category as guidance.”

In addition, Kilaru said, this guidance is driven by a higher level of evidence certainty than the mostly retrospective evidence that was previously available.

She cautioned that few downgraded risk categories are likely to cause consternation among physicians who have been operating without the benefit of larger meta-analyses of HBVr in new medication categories. “For example, the prior guidance had put anti-TNF as of moderate risk for hepatitis B core–positive-only patients and is now downgraded to low risk.” And other medications such as immune checkpoint inhibitors, which seemed to pose at least moderate risk based on smaller, retrospective studies are now considered to be in the low-risk category.

“It may take some time for these recommendations to be adopted, especially for physicians in the community who have seen fatal or severe reactivations in the past few years,” Kilaru said.

Kilaru pointed out that the guidance update does not clearly cover some standard immunosuppressive therapies used in autoimmune, rheumatologic, and posttransplant regimens, such as mycophenolate, tacrolimus, and cyclosporine. Nor does it address HBVr risk in some liver cancer treatments such as yttrium-90, which have been associated with reports of HBV reactivation.

 

The Future

According to Simon, more data are needed to better estimate HBVr risk in several important settings, including treatment with the most recently approved immunosuppressive drugs for which data are still limited, as well as combination treatments.

Kilaru noted that guideline updates such as this become increasingly relevant as cancer diagnoses rise and hepatitis B exposure and detection increase as well.

The AGA panel acknowledged that uncertainty remains in some patient risk categorizations. “As the armamentarium of immunotherapeutics evolves, it will be crucial to search for, use, and maintain studies that provide baseline HBV serologies; include a clear definition of HBVr; and enroll a large, nonselective cohort that can guide categorization of risk of HBVr,” the panelists wrote.

AGA provided all financial support for the development of this guideline. No funding from industry was offered or accepted to support the writing effort.

The authors reported no relevant competing interests, but one coauthor is an adviser for Gilead Sciences, and other authors disclosed various relationships with multiple private sector companies. Kilaru had no competing interests to disclose.

A version of this article appeared on Medscape.com.

A newly validated risk stratification tool could potentially improve hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis, based to a recent phase 3 biomarker validation study.

The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.

“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.” 

The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.

The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.

In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.

In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.

The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection. 

Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.

“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.

A newly validated risk stratification tool could potentially improve hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis, based to a recent phase 3 biomarker validation study.

The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.

“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.” 

The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.

The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.

In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.

In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.

The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection. 

Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.

“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.

A newly validated risk stratification tool could potentially improve hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis, based to a recent phase 3 biomarker validation study.

The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.

“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.” 

The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.

The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.

In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.

In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.

The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection. 

Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.

“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.

Clinicians should be aware of how to manage certain gastrointestinal (GI) and liver conditions associated with pregnancy, such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy, according to a clinical practice update (CPU) from the American Gastroenterological Association.

Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.  

 

“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.  

“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”  

The update was published online in Gastroenterology.  

 

Pregnancy-Related Concerns

The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.

Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.  

At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.  

Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.  

Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.  

For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.  

For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.  

For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.  

Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.  

Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.  

In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.  

Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.  

Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal. 

Pregnancy-Related Updates in Practice

Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.

“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”  

Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.  

“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”  

The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians should be aware of how to manage certain gastrointestinal (GI) and liver conditions associated with pregnancy, such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy, according to a clinical practice update (CPU) from the American Gastroenterological Association.

Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.  

 

“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.  

“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”  

The update was published online in Gastroenterology.  

 

Pregnancy-Related Concerns

The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.

Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.  

At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.  

Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.  

Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.  

For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.  

For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.  

For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.  

Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.  

Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.  

In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.  

Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.  

Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal. 

Pregnancy-Related Updates in Practice

Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.

“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”  

Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.  

“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”  

The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians should be aware of how to manage certain gastrointestinal (GI) and liver conditions associated with pregnancy, such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy, according to a clinical practice update (CPU) from the American Gastroenterological Association.

Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.  

 

“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.  

“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”  

The update was published online in Gastroenterology.  

 

Pregnancy-Related Concerns

The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.

Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.  

At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.  

Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.  

Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.  

For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.  

For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.  

For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.  

Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.  

Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.  

In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.  

Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.  

Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal. 

Pregnancy-Related Updates in Practice

Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.

“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”  

Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.  

“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”  

The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.

A version of this article appeared on Medscape.com.

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

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

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

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

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log₁₀ IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log₁₀ IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log₁₀ IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log₁₀ IU/mL or > 8 log₁₀ IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log₁₀ IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

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

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Hispanic adults in the US experience significantly higher risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH), compared with non-Hispanic adults, according to a new systematic review and meta-analysis.

These findings underscore worsening health disparities in MASLD management and outcomes in this patient population, Kaleb Tesfai, BS, of the University of California, San Diego, and colleagues reported.

Previously, a 2018 meta-analysis found that Hispanic individuals had a higher MASLD prevalence than non-Hispanic White and Black individuals, along with an elevated relative risk of MASH. 

“In the setting of the evolving obesity epidemic, prevalence of MASLD has increased and characteristics of patient populations of interest have changed since the time of this prior meta-analysis,” Mr. Tesfai and colleagues wrote in Clinical Gastroenterology and Hepatology. “Importantly, MASH has become a leading indication for liver transplant, thereby impacting long-term clinical outcomes. As such, accurate, updated prevalence rates and relative risk estimates of MASLD, MASH, advanced fibrosis/cirrhosis, and clinical outcomes for Hispanic adults in the US remain poorly characterized.”

The present meta-analysis focused specifically on Hispanic adults in the United States; it compared their disease prevalence, severity, and risk to non-Hispanic adults. Twenty-two studies, conducted between January 1, 2010, and December 31, 2023, were included, comprising 756,088 participants, of whom 62,072 were Hispanic. 

Study eligibility required reported data on the prevalence of MASLD, MASH, or advanced fibrosis, as well as racial or ethnic subgroup analyses. Studies were excluded if they did not use validated diagnostic methods, such as liver biopsy or imaging, or if they lacked stratification by Hispanic ethnicity. Prevalence estimates and relative risks were calculated using random-effects models. The analysis also accounted for potential confounding factors, including demographic characteristics, metabolic comorbidities, and social determinants of health (SDOH).

The pooled prevalence of MASLD among Hispanic adults was 41% (95% CI, 30%-52%), compared with 27% in non-Hispanic populations, reflecting a relative risk (RR) of 1.50 (95% CI, 1.32-1.69). For MASH, the pooled prevalence among Hispanic adults with MASLD was 61% (95% CI, 39%-82%), with an RR of 1.42 (95% CI, 1.04-1.93), compared with non-Hispanic adults.

“Our systematic review and meta-analysis highlights the worsening health disparities experienced by Hispanic adults in the US, with significant increase in the relative risk of MASLD and MASH in contemporary cohorts compared with prior estimates,” the investigators wrote. 

Despite these elevated risks for MASLD and MASH, advanced fibrosis and cirrhosis did not show statistically significant differences between Hispanic and non-Hispanic populations. 

The study also characterized the relationship between SDOH and detected health disparities. Adjustments for factors such as income, education, and health care access eliminated the independent association between Hispanic and MASLD risk, suggesting that these structural inequities play a meaningful role in disease disparities. 

Still, genetic factors, including PNPLA3 and TM6SF2 risk alleles, were identified as contributors to the higher disease burden in Hispanic populations.

Mr. Tesfai and colleagues called for prospective studies with standardized outcome definitions to better understand risks of advanced fibrosis and cirrhosis, as well as long-term clinical outcomes. In addition, they recommended further investigation of SDOH to determine optimal intervention targets.

“Public health initiatives focused on increasing screening for MASLD and MASH and enhancing health care delivery for this high-risk group are critically needed to optimize health outcomes for Hispanic adults in the US,” they concluded.This study was supported by various institutes at the National Institutes of Health, Gilead Sciences, and the SDSU-UCSD CREATE Partnership. The investigators disclosed additional relationships with Eli Lilly, Galmed, Pfizer, and others.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.

Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) predicts long-term outcomes among pediatric patients with biliary atresia, according to investigators.

These findings suggest that LSM may serve as a noninvasive tool for risk stratification and treatment planning in this population, reported lead author Jean P. Molleston, MD, of Indiana University School of Medicine, Indianapolis, and colleagues.

 

“Biliary atresia is frequently complicated by hepatic fibrosis with progression to cirrhosis and portal hypertension manifested by ascites, hepatopulmonary syndrome, and variceal bleeding,” the investigators wrote in Gastroenterology. “The ability to predict these outcomes can inform clinical decision-making.”

To this end, VCTE has been gaining increasing support in the pediatric setting.

“Advantages of VCTE over liver biopsy include convenience, cost, sampling bias, and risk,” the investigators wrote. “VCTE potentially allows (1) fibrosis estimation, (2) prediction of portal hypertension complications/survival, and (3) ability to noninvasively monitor liver stiffness as a fibrosis surrogate.”

The present multicenter study aimed to gauge the prognostic utility of VCTE among 254 patients, aged 21 years or younger, with biliary atresia. All patients had a valid baseline LSM, plus longitudinal clinical and laboratory data drawn from studies by the Childhood Liver Disease Research Network (ChiLDReN). Liver stiffness was assessed noninvasively with FibroScan devices, adhering to protocols that required at least 10 valid measurements and a variability of less than 30%.

The primary outcomes were survival with native liver (SNL), defined as the time to liver transplantation or death, and a composite measure of liver-related events, including the first occurrence of transplantation, death, ascites, variceal bleeding, or hepatopulmonary syndrome. Secondary outcomes focused on the trajectory of platelet decline, a marker of disease progression. The study also explored the relationship between baseline LSM and conventional biomarkers, including platelet count, albumin, and bilirubin.

LSM was a strong predictor of long-term outcomes. Specifically, Kaplan-Meier analysis showed significant differences in 5-year SNL across LSM strata (P < .001). Children with LSM values less than 10 kPa had excellent 5-year SNL rates (LSM 10 to < 15 kPa, 88.9%; 95% CI, 75.1-95.3%), while those with LSM of at least 15 kPa exhibited substantially lower 5-year SNL (58.9%; 95% CI, 46.0-69.7%).

Similarly, event-free survival (EFS) rates declined as LSM values increased (P < .001). Participants with LSM less than 10 kPa had a 5-year EFS rate of 92.2% versus with 61.2% for those with LSM of at least 15 kPa.

LSM also predicted platelet decline. For every twofold increase in baseline LSM, platelet counts declined by an additional 4,000/mm³ per year (P < .001). This association was illustrated through predicted trajectories for participants with LSM values of 4, 7, 12, 18, and 42 kPa, corresponding to different percentiles of disease severity.

Cox proportional hazards analysis indicated that a two-fold increase in LSM was associated with a hazard ratio of 3.3 (P < .001) for liver transplant or death. While LSM had good discrimination on its own (C statistic = 0.83), it did not significantly improve predictive accuracy when added to models based on platelet count, albumin, and bilirubin.

“This noninvasive measurement could potentially be used to predict natural history, stratify patients for clinical trials, plan interventions, and provide anticipatory guidance,” Molleston and colleagues concluded. This study was supported by grants from the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Childhood Liver Disease Research Network; and others. The investigators disclosed no conflicts of interest.