Zobair Younossi, MD, MPH, is chairman of the Global NASH/MASH Council and professor and chairman of Beatty Liver and Obesity Research at Inova Health System.

Zobair Younossi, MD, MPH

Diagnostic Performance of NITs Across MASLD Subgroups, With Zobair Younossi, MD

As metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise globally, the need for accurate, accessible risk stratification has never been greater. Historically, clinicians have relied on liver biopsy to identify the subgroup of patients with metabolic dysfunction–associated steatohepatitis (MASH) at the greatest risk for progression to cirrhosis, liver cancer, and liver-related mortality.

Because biopsy is invasive, costly, and not without risk, the field of hepatology has grown increasingly reluctant to rely on it for widespread screening and longitudinal monitoring. As Zobair Younossi, MD, professor and chairman of the Global NASH Council, explains in an interview with 

, the past decade has been defined by efforts to develop noninvasive alternatives that can match biopsy not only in staging accuracy but also in predicting long-term outcomes.

“NITs were first established on a liver biopsy to see if they're accurately predicting the stage that we want to look for,” he explained. “More recently, there is also data to suggest that these NITs predict outcome as well as liver biopsy, and maybe sometimes even better than a liver biopsy, which makes them ideal for clinical use and also for use in clinical trials.”

Specifically, Younossi references 3 main categories of noninvasive tests:

Imaging modalities like VCTE, shear wave elastography, and MRE

He additionally describes combination tests leveraging combined clinical data from existing NITs, including the FAST score, AGILE 3, and AGILE 4.

Younossi’s research, a trio of sequentially published papers, has explored how NITs perform across regions, how well they predict liver-related outcomes compared with biopsy, and how their accuracy varies in key subgroups.

Of note, while all NITs demonstrated outcome prediction comparable to, and in some cases better than, biopsy, their performance was not uniform. He says FIB-4, for example, performs less reliably in patients at extremes of age and in those with diabetes, and regional variability was observed, with weaker performance in South Asia and Latin America. In contrast, liver stiffness measurement was less affected by age or diabetes but was influenced by severe obesity. Among the available tools, AGILE 3 and AGILE 4 emerged as particularly stable across regions and subgroups.

Clinically, Younossi emphasizes a stepwise algorithm. FIB-4 remains the recommended first-line test to identify patients at low risk who can be monitored periodically versus those who warrant second-line assessment with VCTE or ELF. Beyond risk stratification, he says NITs now guide treatment selection, particularly for noncirrhotic MASH patients eligible for recently approved agents such as resmetirom or semaglutide and enable longitudinal monitoring.

Editors’ Note: Younossi reports relevant disclosures with Intercept, Cymabay, Boehringer Ingelheim, Ipsen, BMS, GSK, Novo Nordisk, Siemens, Madridgal, Merck, Aligos, Akero, Sanofi and Abbott.

Younossi ZM, de Avila L, Petta S, et al. Diagnostic Accuracy of Non-Invasive Tests for MASLD Across Age, Type 2 Diabetes, and Obesity Subgroups: A Multinational Study. 

. Published online January 28, 2026. doi:10.1016/j.cgh.2026.01.016

Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed February 12, 2026. 

https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed February 12, 2026. 

https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash

Videos

Younossi explains the growing interest in NITs for MASLD and reviews his research on their performance in age, diabetes, and obesity subgroups.

Diagnostic Performance of NITs Across MASLD Subgroups, With Zobair Younossi, MD, MPH

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

Health-Related Quality of Life Improvements With Resmetirom, With Zobair Younossi, MD, MPH

While the hepatic benefits of resmetirom (Rezdiffra) are well established following its US Food and Drug Administration approval for metabolic dysfunction-associated steatohepatitis (MASH), new research is shedding light on the treatment’s impact on health-related quality of life (HRQoL).

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

 by Zobair Younossi, MD, MPH, chairman of the Global NASH/MASH Council and professor and chairman of Beatty Liver and Obesity Research at Inova Health System, and highlight improvements in select disease-specific HRQoL scores among patients without or with cirrhosis due to MASLD treated with resmetirom in the phase 3 MAESTRO-NAFLD trial.

“As physicians, we always look at biochemical, physiological, liver histology or NITs as ‘important’ endpoints or outcomes, but from a patient's perspective, it's how they feel, how they experience the disease or the treatment,” Younossi explained to 

. “To me, that should be the most important, because if you're going to do patient-centered care, then the patient has to be at the center…. In my opinion, putting the patient-reported outcome at least on an equal footing to the physiological, biochemical and other outcomes is extremely important.”

Research he presented at AASLD explored the HRQoL impacts of treatment with resmetirom in MAESTRO-NAFLD. Patients with MASLD with cirrhosis (CP-A) or MASLD without cirrhosis were enrolled in a 52-week, phase 3 double-blind placebo-controlled study of resmetirom (Period 1 of MAESTRO-NAFLD) and upon treatment completion, were offered to enroll in a 52-week open-label extension study of resmetirom (Period 2). HRQoL was assessed using LDQOL, CLDQ-NAFLD and WPAI throughout treatment period 1 at baseline, week 24, week 52 and treatment Period 2 at day 1, week 12, week 28, and week 52.

For non-cirrhotic MASLD, PDFF response was defined as a decrease in MRI-PDFF ≥30% from baseline. For cirrhotic MASLD, it was defined as ≥20% decrease in MRI-PDFF if baseline MRI-PDFF was >5%.

MAESTRO NAFLD included a total of 1307 MASLD patients. Of these, 193 had cirrhosis (23% with baseline MRI-PDFF ≤5%) and 1114 were without cirrhosis (baseline MRI-PDFF ≥8%).

At baseline, HRQoL scores of patients with cirrhosis were significantly lower (up to -16% of score range) for all 6 domains of CLDQNAFLD, 14/17 domains of LDQOL, Activity Impairment of WPAI (p<0.05). Among patients with cirrhosis, there was no significant difference in baseline HRQL scores between those with MRI-PDFF ≤5% and >5% (all 

>.05). By week 24 of treatment with resmetirom during period 1, patients with cirrhosis experienced improvements in Worry (CLDQ-NAFLD) and Health Distress (LDQOL) up to +4% of score range which sustained by week 52 and throughout Period 2 (

In cirrhotic patients with MRI-PDFF >5%, PDFF response by Period 1 week 52, there was an improvement in Stigma score (LDQOL; mean change, +4.0 vs -5.7; 

= .011). By weeks 24 and 52 of treatment, non-cirrhotic patients receiving placebo experienced worsening of HRQL in some physical health-related domains of LDQOL (mean decrease up to -5%; 

<.05) while no decreases were observed in non-cirrhotic patients treated with resmetirom.

Additionally, non-cirrhotic patients receiving resmetirom experienced improvement in Abdominal and Worry domains of CLDQ-NAFLD and Health Distress of LDQOL (mean increase up to +5% of score range size), while no similar improvements were observed in placebo (all 

>.05). Non-cirrhotic patients with PDFF response also experienced improvements in Abdominal and Worry scores (up to +7%), which were greater than those seen in placebo or non-responders.

“From my perspective, the PROs really have 2 important aspects in this context,” Younossi explained. “One is that the drug that you're using is not worsening patients' quality of life, because some drugs, historically, interferon for hepatitis C, have caused a lot of side effects, and quality of life actually took a dive. Here, not only are you not seeing a decline in quality of life, but you're actually seeing improvement, so you're improving our patient's experience and how they feel.”

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

Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed November 11, 2025. 

Younossi Z, Nader F, Labriola D, et al. Improvement In Health-Related Quality of Life After Treatment with Resmetirom in Cirrhotic and Non-Cirrhotic Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Data From MAESTRO‑NAFLD. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

Younossi explains the importance of patient-reported outcomes and assessing HRQoL, breaking down findings from an analysis of the MAESTRO-NAFLD trial of resmetirom.