Liver Disease

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

BERLIN — Hepatocellular carcinoma (HCC) could be detected earlier, treated more effectively, and prevented more widely if European countries adopt structured, risk-stratified surveillance alongside systemic public health strategies, according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).

The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 . 

“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.

“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.

HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.

 

Risk-Stratified HCC Surveillance

In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.

EASL’s key recommendations include:

• Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
• Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
• Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
• A de-escalation in low-risk individuals
• Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions

Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.

Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”

Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”

Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.

 

Barriers to Screening Uptake

HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.

Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”

However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.

Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.

 

Expanded Training and Public Health Measures

The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.

The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.

“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.

Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.

A version of this article appeared on Medscape.com.

BERLIN — Hepatocellular carcinoma (HCC) could be detected earlier, treated more effectively, and prevented more widely if European countries adopt structured, risk-stratified surveillance alongside systemic public health strategies, according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).

The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 . 

“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.

“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.

HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.

 

Risk-Stratified HCC Surveillance

In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.

EASL’s key recommendations include:

• Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
• Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
• Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
• A de-escalation in low-risk individuals
• Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions

Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.

Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”

Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”

Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.

 

Barriers to Screening Uptake

HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.

Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”

However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.

Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.

 

Expanded Training and Public Health Measures

The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.

The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.

“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.

Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.

A version of this article appeared on Medscape.com.

BERLIN — Hepatocellular carcinoma (HCC) could be detected earlier, treated more effectively, and prevented more widely if European countries adopt structured, risk-stratified surveillance alongside systemic public health strategies, according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).

The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 . 

“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.

“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.

HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.

 

Risk-Stratified HCC Surveillance

In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.

EASL’s key recommendations include:

• Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
• Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
• Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
• A de-escalation in low-risk individuals
• Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions

Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.

Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”

Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”

Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.

 

Barriers to Screening Uptake

HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.

Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”

However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.

Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.

 

Expanded Training and Public Health Measures

The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.

The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.

“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.

Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.

A version of this article appeared on Medscape.com.

BERLIN — A novel investigational ileal bile acid transporter (IBAT) inhibitor, linerixibat, significantly and rapidly reduced cholestatic pruritus in patients with primary biliary cholangitis (PBC), according to phase 3 results from the GLISTEN trial.

The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.

“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.

Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.

Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.

 

The GLISTEN Trial

Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.

Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).

The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.

The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.

 

24-Week Data

Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.

Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).

“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.

In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.

Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).

“In summary, it is a safe drug from our perspective,” said Kremer.

 

Focusing on Symptoms, Not Biochemical Response

Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”

Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.

“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”

Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.

Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.

The GLISTEN study was funded by GSK.

A version of this article appeared on Medscape.com.

BERLIN — A novel investigational ileal bile acid transporter (IBAT) inhibitor, linerixibat, significantly and rapidly reduced cholestatic pruritus in patients with primary biliary cholangitis (PBC), according to phase 3 results from the GLISTEN trial.

The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.

“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.

Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.

Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.

 

The GLISTEN Trial

Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.

Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).

The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.

The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.

 

24-Week Data

Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.

Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).

“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.

In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.

Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).

“In summary, it is a safe drug from our perspective,” said Kremer.

 

Focusing on Symptoms, Not Biochemical Response

Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”

Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.

“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”

Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.

Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.

The GLISTEN study was funded by GSK.

A version of this article appeared on Medscape.com.

BERLIN — A novel investigational ileal bile acid transporter (IBAT) inhibitor, linerixibat, significantly and rapidly reduced cholestatic pruritus in patients with primary biliary cholangitis (PBC), according to phase 3 results from the GLISTEN trial.

The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.

“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.

Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.

Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.

 

The GLISTEN Trial

Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.

Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).

The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.

The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.

 

24-Week Data

Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.

Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).

“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.

In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.

Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).

“In summary, it is a safe drug from our perspective,” said Kremer.

 

Focusing on Symptoms, Not Biochemical Response

Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”

Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.

“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”

Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.

Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.

The GLISTEN study was funded by GSK.

A version of this article appeared on Medscape.com.

Global consensus recommendations were recently published for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).

These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.

“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”

To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.

Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.

The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”

For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.

Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.

Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.

The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.

Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.

“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.

The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.







 

Global consensus recommendations were recently published for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).

These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.

“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”

To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.

Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.

The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”

For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.

Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.

Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.

The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.

Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.

“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.

The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.







 

Global consensus recommendations were recently published for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).

These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.

“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”

To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.

Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.

The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”

For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.

Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.

Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.

The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.

Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.

“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.

The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.