Andreas Kremer, MD, PhD, MHBA, is the head of hepatology at University Hospital Zurich in Switzerland.

Andreas Kremer, MD, PhD, MHBA

This Year in Hepatology: New MASLD Therapies, HBV Updates, and More

2025 has marked a clear turning point in 

, bringing advances that are reshaping both the scientific landscape and everyday clinical practice. After years defined by limited therapeutic options and slow-moving pipelines, this year delivered transformative progress, from the long-awaited arrival of effective pharmacologic treatments for 

, cholestatic liver diseases, portal hypertension, and alcohol-associated liver disease.

However, the momentum extends well beyond new drugs. Emerging noninvasive diagnostics, evolving disease definitions, AI-enabled pathology, and increasingly patient-centered care models are redefining how clinicians detect, stage, and manage chronic liver disease. Together, these shifts signal a rapidly accelerating era in hepatology that is expanding treatment opportunities while reshaping clinical expectations.

To capture the breadth of this evolution, the editorial team of 

 invited 7 leading experts to weigh in on the most important advances of 2025:

, an assistant professor of medicine and director of the IHEAL Clinic at the University of North Carolina School of Medicine:

I think in the past year, the biggest news has been the increasing use of medications to treat metabolic dysfunction associated-steatotic liver disease, formerly known as fatty liver disease. The weight loss medications, the GLP-1 receptor agonists, are really changing the game for this disease process. Resmetirom is another new medication we have, and just given the sheer number of patients that we have with this disease process, now finally having medications to treat them, albeit with insurance barriers, which we're working on, but I think it's really promising to be able to at least have options for these patients. Hopefully the government and local partners can help bring the prices of these medications down and increase access, because they really are beneficial.

, chairman of the Global NASH/MASH Council and professor and chairman of Beatty Liver and Obesity Research at Inova Health System:

I think the biggest news in hepatology is the drugs that we are developing for MASH. Resmetirom, semaglutide, and probably the new drugs with FGF21s, so hopefully we'll see the results next year. There is also a lot of interest in other liver diseases, understanding the dynamic nature of what we call steatotic liver disease between MASLD, MetALD, and ALD, that this is a dynamic disease that goes back and forth. So that's an important concept to understand, and there is also some hope in terms of better treatment for viral hepatitis, especially delta hepatitis, which may not be a major issue in the United States but is a major issue in some other parts of the world. So all of these actually gave me more hope that we are going to see more and more innovation and interest in this area.

, a transplant hepatologist and assistant professor of medicine at Massachusetts General Hospital and Harvard Medical School:

There have been a few pieces of breaking news in the past year. First, I'd say the most important is steatotic liver disease, and now we finally have 2 approved medications to treat patients with MASH. We used to have no other, or very little, options, except for exercise and lifestyle modification, which is very important, but also hard to do. But now we have medications that actually have been proven to be effective in reducing steatosis and also fibrosis in those patients, so it can prevent further development of advanced liver disease.

Obviously, in addition to that, we're also trying to use a combination of pharmacotherapy and behavioral therapy so once patients lose weight, they'll continue to stay in that weight for a long period of time, and that disease can be controlled or even resolved. In addition to that, what I have noticed is that alcohol-related liver disease continues to be paid attention to. In our liver disease society, we have more researchers, we have more findings in this field, and more and more people are realizing that pharmacotherapy is something that could be utilized by us to manage patients with alcohol-related liver disease, and integrated clinics actually are more utilized across the academic medical centers to manage those patients.

The third part that I've noticed is there are more lectures and more attention that is paid to address psychosocial and structural determinants in patients with chronic liver disease, for example, stigma. This year, we have a specific session for stigma and also psychosocial structural barriers. I think we're paying more and more attention in this area, which is very important, because how patients feel about their disease is also extremely important as to how we can manage and help their disease itself.

, the head of hepatology at University Hospital Zurich:

I don’t want to break it down to one piece of biggest news. I think we have seen a lot of changes from treating underlying diseases, such as in rare cholestatic liver disease the switch to symptom burden, which is more and more addressed in many disorders, which I think is very important to our patients. They sometimes care more about improved symptoms rather than an improved laboratory parameter.

We also see great developments in the field of MASLD and also fibrotic or cirrhotic MASLD. The problem is so far, we have always relied on histology, and we see clear trends towards artificial intelligence based pathology investigations or noninvasive tests to overcome the need for biopsy on a study drug, where we, hopefully, in the future, have certain definitions that indicate this is associated with improved histology, so that we can avoid biopsy and purely rely on noninvasive parameters, whether this is an Agile 4 combined laboratory parameter or a certain elastography-based measurement needs to be shown in the end. There's a clear trend in this large disease moving away.

I think these are important messages and various other aspects a little bit, depending on whom you ask, but I think quite intriguing news we have learned here in Washington, DC.

, chief academic officer of Summit Clinical Research and director of the Steatotic Liver Program at North Shore Gastroenterology:

I think being in the field of hepatology has been very exciting in the last few years. We have new treatments that are being developed for hepatitis B to achieve functional cure, and I think this will be a great addition for these patients. We also see new therapeutics being developed to treat portal hypertension, and these patients have very advanced liver disease. They're on the cusp of decompensation, so if we can take them back into a more stable stage of their disease, that will be a very important development. We are also seeing many new therapeutics to treat cholestatic liver disease, both PSC and PBC, and we also see treatments for genetic cholestasis diseases like progressive familial intrahepatic cholestasis. There's many, many new biomarkers that are being developed and screening algorithms to increase awareness of chronic liver disease in general, so I couldn't be happier to be a hepatologist.

, a professor at the Baruch S. Blumberg Institute and president of the Hepatitis B Foundation:

We have 2 new treatment guidelines for hepatitis B. EASL came out with their hepatitis B guidelines earlier in the year, and AASLD just came out with their updated hepatitis B guidelines a few days ago. We're excited to see how those are going to be implemented. We are excited as a community to have expanded treatment guidelines, and one of the central tenets of both of those guidelines is shared decision-making. We're very, very pleased to see that medical societies are paying attention to what the patient wants and understanding that the decision to initiate treatment should be a shared one between a clinician and a patient.

, a professor of medicine at Houston Methodist Hospital and co-chairman of Summit Clinical Research’s Board of Directors 

I think there are a million biggest pieces of news this year. We can talk about that for an hour, but I think the MASH field just got another big boost. There were multiple acquisitions this year, the efruxiferm acquisition, the pegozafermin acquisition, and the efimosfermin acquisition. In addition, pemvidutide came with a primary endpoint, so now we have multiple attractive phase 3 trials. With having big sponsors, I think we'll start seeing combination therapy and more trials going on. This is probably the hottest year for the MASH field ever, and I look forward to many good years coming down.

 reports relevant disclosures with Intercept, Gilead, Boehringer Ingelheim, Ipsen, Bristol-Myers Squibb, GSK, NovoNordisk, Siemens, Madridgal, Merck, Akero and Abbott. 

 reports relevant disclosures with AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others. 

 reports relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Rivus, Takeda, and others. 

 reports relevant disclosures with Gilead Sciences, GlaxoSmithKline, Vir Biotechnology, Dynavax Technologies, and Roche. 

 reports relevant disclosures with Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda, 89BIO, Altimmune, Boehringer Ingelheim, and others.

Younossi ZM, Zelber-Sagi S, Lazarus JV, et al. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025;169(5):1017-1032.e2. doi:

​Bansal MB, Patton H, Morgan TR, Carr RM, Dranoff JA, Allen AM. Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD Practice Guidance. Hepatology. Published online November 7, 2025. doi:

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025;83(2):502-583. doi:

Articles

The year 2025 has marked significant advancements in hepatology, transforming both scientific research and clinical practice. Notable progress includes the introduction of effective pharmacologic treatments for MASLD/MASH, innovations in viral hepatitis, cholestatic liver diseases, and alcohol-associated liver disease. Additionally, noninvasive diagnostics, AI-enabled pathology, and patient-centered care models are redefining chronic liver disease management. Experts highlight the importance of new medications, the dynamic nature of steatotic liver disease, and the role of psychosocial factors in patient care, signaling a rapidly evolving era in hepatology.

Recent advancements in hepatology highlight new medications for metabolic dysfunction and liver diseases, promising improved patient outcomes and treatment options.

2025 in Hepatology: New MASLD Therapies, HBV Updates, and More

New Insights into Seladelpar for PBC at AASLD 2025, With Andreas Kremer, MD, PhD

For many years, obeticholic acid was the sole second-line treatment option for patients with primary biliary cholangitis (PBC) who did not respond to or could not tolerate first-line ursodeoxycholic acid. However, in 2024, the PBC treatment landscape saw the addition of 2 new second-line therapies, one being the oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist seladelpar.

The August 2024 accelerated approval was based on data from the phase 3 RESPONSE study, which showed 62% of patients treated with seladelpar achieved the primary endpoint of composite biochemical response at month 12 versus 20% of patients taking placebo.

American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025

, new data provided clinicians with additional insight into seladelpar’s benefit for patients with PBC, including its disease-modifying and symptom-relieving effects. In an on-site interview at the conference, Andreas Kremer, MD, PhD, head of hepatology at University Hospital Zurich, broke down some of the key research and its clinical implications.

“[Seladelpar] has proven to be efficacious in a phase 3 study in regard to anticholestatic, anti-inflammatory properties, but there was also a prespecified secondary endpoint in regard to worst itch NRS improvement that was met, and this was very convincingly shown for those patients with moderate to severe pruritus,” Kremer explained to 

At AASLD, late-breaking RESPONSE and ASSURE open-label extension study data shed light on long-term pruritus outcomes with seladelpar, highlighting sustained, clinically meaningful improvement in itch among patients with moderate-to-severe pruritus in RESPONSE and with up to 30 months of treatment.

Additional analyses from RESPONSE showed improvements in itch-related disability and decreased bodily distribution of itch following treatment with seladelpar as well as greater improvements in their general health and wellbeing after 12 months.

“This adds on to the antipruritic properties of this drug, which is very reassuring, and we have also seen efficacy for several years,” Kremer said.

Editors’ Note: Relevant disclosures for Kremer include AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. August 14, 2024. Accessed November 12, 2025. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Hirschfield G. Seladelpar’s Long-Term Benefit for Pruritus in PBC, With Gideon Hirschfield, FRCP, PhD. HCPLive. November 8, 2025. Accessed November 12, 2025. 

https://www.hcplive.com/view/seladelpar-long-term-benefit-pruritus-pbc-with-gideon-hirschfield-frcp-phd

Kremer A, Jones DE, Mayo M, et al. Reduction in Itch-Associated Disability and Pruritus Distribution in Patients With Primary Biliary Cholangitis Treated With Seladelpar in the RESPONSE Trial. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Kumar S, Kremer A, Londono MC, et al. Improvements in Patient-Reported General Health and Well-Being in Patients With Primary Biliary Cholangitis Treated With Seladelpar in the RESPONSE Trial. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Videos

Kremer breaks down new data on the disease-modifying and symptom-relieving effects of seladelpar presented at AASLD The Liver Meeting 2025.

New Insights Into Seladelpar for PBC at AASLD 2025, With Andreas Kremer, MD, PhD

GLISTEN: Linerixibat Improves Biomarkers and Itch in Patients With PBC, With Andreas Kremer, MD, PhD, MHBA

Results from GLISTEN, the largest investigational study of pruritus in 

 (PBC), highlight the effects of linerixibat on pharmacodynamic biomarkers of bile acid metabolism and mediators of cholestatic pruritus in this patient population.

Andreas Kremer, MD, PhD, MHBA, the head of hepatology in the department of gastroenterology at the University Hospital Zurich, presented the data at the 

. The findings hold important implications for PBC management, showing increases in serum C4 and reductions in FGF-19, total serum bile acids (TSBA), autotaxin (ATX), and interleukin-31 (IL-31), validating the biologic mechanism of linerixibat and its impact on cholestatic pruritus in PBC.

“If you look carefully at the baseline characteristics, 50% of patients were on guideline-recommended therapy yet continued to experience mostly severe itch, clearly illustrating a significant unmet clinical need,” Kremer said in an interview with 

. “Linerixibat, an ileal bile acid transport inhibitor, demonstrated significant improvement in itch over 24 weeks of therapy, as well as in sleep interference and other related parameters.”

Cholestatic pruritus refers to the bile flow impairment caused by PBC, which creates symptoms of itch, and has an 89% occurrence in the patient population. Linerixibat, an ileal bile acid transporter inhibitor, blocks bile acid reabsorption in the terminal ileum, targeting a root cause of cholestatic pruritus. 

 addressed an unmet need for symptom-specific therapy targeting pruritus.

GLISTEN was a phase 3, randomized, double-blind, placebo-controlled study evaluating pruritus symptoms and pharmacodynamic biomarkers in 238 patients with PBC and moderate-to-severe pruritus. During the 24-week primary intervention period, patients received linerixibat 40 mg twice daily (n = 119) or placebo (n = 119). In the subsequent 8-week crossover period, patients either maintained or switched treatment. Biomarkers were assessed at baseline and every 4 weeks through week 32. A post hoc analysis evaluated correlations between changes from baseline in biomarker levels and weekly itch scores.

The phase 3 findings presented at AASLD aligned with the pharmacology of linerixibat, showing changes in key pharmacodynamic biomarkers reflecting bile acid synthesis and feedback regulation with significant increases in serum C4 (95% confidence interval [CI], 2.22-2.93; 

and decreases in FGF-19 (95% CI, 0.51-0.65; 

<.001) through week 24. Additionally, investigators noted significant reductions in pruritus mediators TSBA (95% CI, 0.66-0.85; 

The crossover period demonstrated reduced C4 levels and increases in FGF-19, TSBA, ATX, and IL-31 in patients who switched from linerixibat to placebo.

In the post hoc analysis, investigators observed a weak correlation between reductions in TSBA (

= .05) with reductions in pruritus at week 4. Additionally, they noted a weak but statistically significant correlation between changes in C4 (r = -.289, 

= .028) with reductions in pruritus over time.

Kremer and colleagues noted the recorded changes in biomarkers and itch scores from baseline were reversible upon linerixibat treatment discontinuation.

“We gained more insights into how [linerixibat] works and are very happy to see these developments," said Kremer. "Hopefully, in the near future, we will have an in-label drug to treat pruritus in PBC.”

Editor’s Note: Kremer reports relevant disclosures with Gilead, Intercept, Roche, AbbVie, and others.

Kremer A, Bowlus C, Lennie J, et al. Impact of linerixibat on pharmacodynamic biomarkers and mediators of cholestatic pruritus in primary biliary cholangitis (PBC) in the Phase 3 GLISTEN study. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Hirschfield GM, Bowlus CL, Jones DEJ, et al. Linerixibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. 

https://doi.org/10.1016/s2468-1253(25)00192-x

GSK. Linerixibat shows positive Phase III results in cholestatic pruritus (relentless itch) in primary biliary cholangitis (PBC). Published 2024. Accessed November 12, 2025. 

https://www.gsk.com/en-gb/media/press-releases/linerixibat-shows-positive-phase-iii-results-in-cholestatic-pruritus

GLISTEN AASLD-presented data show linerixibat reduces biomarkers and itch in PBC, supporting the drug as an ileal bile acid transporter inhibitor.


Long-Term Efficacy and Symptom Relief With Elafibranor in PBC, With Andreas Kremer, MD, PhD

Management of symptoms in primary biliary cholangitis (PBC) has long been one of the most challenging aspects of care. While existing therapies have proven their efficacy for slowing disease progression and reducing cholestasis, many patients continue to struggle with burdensome symptoms of pruritus and fatigue.

Treatment options for these symptoms have been limited, largely off-label, and often hampered by safety, tolerability, or drug-drug interaction concerns. As clinicians become more attentive to patient-reported outcomes, it has become increasingly evident that many patients have not received adequate care for their high symptom burden.

“Historically, we have not managed these symptoms well. We have not asked our patients intensively, because our therapeutic arsenal was very much limited,” Andreas Kremer, MD, PhD, the head of hepatology at University Hospital Zurich, explained to 

Against this backdrop, the emergence of novel peroxisome proliferator-activated receptor (PPAR) agonists offers a meaningful step forward. Among them, elafibranor, a dual PPAR-α/δ agonist, has generated significant interest due to its dual impact on biochemical response and symptom improvement, as emphasized in data from multiple abstracts presented at the 

The first study examined the effect of BMI on elafibranor pharmacokinetics and its efficacy in healthy, overweight, and obese subgroups of the phase 3 ELATIVE trial and found BMI had no clinically relevant effect on exposure to elafibranor or GFT1007 in patients with PBC. Additionally, in the elafibranor arm of ELATIVE, biochemical response rates at week 52 were 56.3%, 46.4% and 44.8% in the healthy weight, overweight and obese subgroups, respectively. Mean changes in ALP levels from baseline to week 52 in the elafibranor arm were –41.5%, –41.8% and –32.3% for elafibranor in the healthy weight, overweight and obese subgroups respectively.

Association Between Symptoms and Cholestatic Biomarkers

Another abstract presented at AASLD assessed the association between improvements in symptoms and cholestatic biomarkers. At baseline, 46/108 and 58/108 patients receiving elafibranor and 20/53 and 30/53 receiving placebo had moderate to severe fatigue according to PFSF 7a and PBC-40 Fatigue scores, respectively. Improvements in PFSF 7a scores were seen within 4 weeks with elafibranor compared with placebo (mean change from baseline, −3.7; SE, 0.9 vs −0.7; SE, 0.9), with further improvements to week 52 (−6.5; SE, 1.2 vs −2.6; SE, 1.6). Changes in PBC-40 Fatigue scores with elafibranor were similar to placebo at week 4 (−2.7; SE, 0.7 vs −2.6; SE, 1.1) but improved to week 52 (−3.6; SE, 1.0 vs −2.1; SE, 1.0).

At baseline, 44/108 patients receiving elafibranor and 22/108 receiving placebo had moderate to severe pruritus. PBC-40 Itch and 5-D Itch improved within 4 weeks with elafibranor versus PBO (−1.4; SE, 0.5 and −2.9; SE, 0.7 vs −0.6; SE, 0.4 and −1.7; SE, 0.8) and continued to week 52 (−2.5; SE, 0.5 and −4.3; SE, 0.7 vs −0.2; SE, 0.7 and −1.7; SE, 1.0).

Proteomic Research on Elafibranor and Fatigue

A third abstract presented at AASLD builds upon a previous analysis presented at the European Association for the Study of the Liver (EASL) Congress 2025, examining the relationship between changes in expression of 10 proteins with a potential role in fatigue or mitochondrial function and fatigue severity with elafibranor. In the study, investigators assessed serum samples collected from patients in the phase 3 ELATIVE trial at baseline and week 52.

Results showed treatment with elafibranor led to expression changes of proteins linked to fatigue or mitochondrial function, significantly correlated with each other and with fatigue improvement and suggesting that PPARα/δ agonism beneficially impacts fatigue-associated pathways linked to mitochondrial function.

“We have seen more and more data that long term safety and efficacy is present for this drug,” Kremer told HCPLive. “It works for up to several years in regard to the anticholestatic and anti-inflammatory properties as measured by laboratory parameters, and we see a long term efficacy in symptom burden improvement, which is very reassuring for such a drug.”

Editors’ Note: Relevant disclosures for Kremer include 

AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

Kremer A, Levy C, Bowlus C, et al. The efficacy of elafibranor is not affected by body mass index in patients with primary biliary cholangitis. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Kremer A, Jones D, Levy C, et al. Changes in fatigue and pruritus in patients with primary biliary cholangitis treated with elafibranor are largely independent from improvements in serum biomarkers. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Brooks A. Elafibranor Benefits Fatigue-Related Pathways Linked to Mitochondrial Function in PBC. HCPLive. November 9, 2025. Accessed November 11, 2025. 

https://www.hcplive.com/view/elafibranor-benefits-fatigue-related-pathways-linked-mitochondrial-function-pbc

Kremer describes recent advancements in the PBC treatment landscape and reviews findings from abstracts on elafibranor presented at AASLD The Liver Meeting 2025.