Sobia Laique, MD, is a gastroenterologist and transplant hepatologist at Cleveland Clinic.

Sobia Laique, MD

Can Metabolic Surgery Reverse MASH Cirrhosis?

For decades, cirrhosis has been understood as an irreversible, fibrotic scar replacing functional liver tissue, largely viewed as an endpoint. However, emerging evidence is challenging that assumption, particularly in the setting of 

metabolic dysfunction-associated steatohepatitis (MASH)

New research presented by Sobia Laique, MD, a gastroenterologist and transplant hepatologist, Chair of the MASLD Task Force, and director of the Multidisciplinary MASLD Center at Cleveland Clinic, at Digestive Disease Week (DDW) 2026 in Chicago, IL, suggests that for select patients with compensated MASH cirrhosis, metabolic bariatric surgery may not only halt disease progression, but actually reverse it.

The research builds on previously published findings from the SPECIAL study, which demonstrated a 72% reduction in major adverse liver outcomes, including variceal hemorrhage, hepatic encephalopathy, liver cancer, need for transplant, and liver-related death, in patients with compensated MASH cirrhosis who underwent MBS.

"When we saw that, it begged the question: did we potentially also reverse the cirrhosis itself?" Laique told 

To explore that question, the team conducted a retrospective cohort study of 30 patients with biopsy-proven compensated MASH cirrhosis who underwent metabolic bariatric surgery between 2004 and 2024 at a single tertiary care center. All patients had F4 fibrosis on baseline biopsy, no prior decompensation or liver transplant, and a median biopsy interval of 6.2 years. The cohort was metabolically advanced, with a mean BMI of 43.7 kg/m² and 87% having diabetes, but carefully selected for compensated disease.

Laique noted that a key insight from the study was methodological: how cirrhosis regression is measured matters. Conventional staging systems, such as the NASH CRN scoring system, define regression as a transition from F4 to F3 or lower, capturing stage changes but potentially missing subtler architectural remodeling, such as thinning or fragmentation of fibrous septa that does not shift the overall stage. When the team applied more granular frameworks, including the Ishak and Beijing classifications, which specifically assess architectural changes within fibrotic tissue, regression rates were meaningfully higher.

Using conventional NASH CRN staging, approximately one-third of patients showed cirrhosis regression. With Ishak scoring, that figure rose to 40%, and with the Beijing classification, to 60%.

"Even if there's a 1-in-3 chance that I have the ability to reverse a patient's disease, that's something I would want to be able to offer them, let alone if that goes up to 40 or 60%," Laique said.

Beyond regression rates, the findings carry broader implications for clinical practice, according to Laique. First, metabolic bariatric surgery can now be positioned as a truly disease-modifying intervention for patients with compensated MASH cirrhosis, one capable of improving long-term outcomes and reversing underlying disease. Second, the field needs to reassess how it measures fibrosis regression, not only in the context of surgical intervention, but also as pharmacologic therapies continue to emerge.

Laique noted that next steps should include prospective studies comparing metabolic bariatric surgery with GLP-1 receptor agonists, as well as mechanistic investigations into what drives cirrhosis regression, work she says her team is actively pursuing at the Cleveland Clinic.

Editor's note: Laique reports no relevant disclosures.

 Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis. 

https://doi.org/10.1038/s41591-024-03480-y

Laique S, Hammad AF, Allende DS, et al. CAN METABOLIC SURGERY REGRESS MASH CIRRHOSIS? EVIDENCE FROM PAIRED BIOPSIES. Presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, May 2-5, 2026.

Videos

New paired biopsy data show histologic regression after metabolic bariatric surgery in compensated MASH patients, challenging the irreversibility of cirrhosis.

Histologic Evidence of MASH Cirrhosis Regression After Metabolic Bariatric Surgery, With Sobia Laique, MD

Metabolic Surgery’s Benefit for MASH-Related Cirrhosis, with Soba Laique, MD

Resmetirom (Rezdiffra) made history in 2024 when it became the first therapeutic to earn US Food and Drug Administration approval for the treatment of 

Although the approval represented a major breakthrough for the field of hepatology and offered a long-awaited pharmacologic treatment option for many affected patients, it did not address the unmet needs of all MASH patients. Indicated specifically for those with noncirrhotic MASH and moderate to advanced fibrosis, resmetirom’s approval did not include patients with MASH-related cirrhosis, a population that still does not have an FDA-approved treatment.

In the absence of medical therapies, recent research has focused on other interventions to help improve outcomes for these patients. Designed to examine the long-term association between metabolic surgery and the risk of progression to major adverse liver outcomes (MALO), the Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) study enrolled patients with compensated biopsy-proven MASH-related cirrhosis and compared outcomes between metabolic surgery and medical management.

“What our findings revealed was a 72% lower risk of incident MALOs and an 80% lower risk of hepatic decompensation in the surgical group, which are staggering numbers to see,” Sobia Laique, MD, a gastroenterologist and transplant hepatologist at Cleveland Clinic, explained in an interview with 

She went on to describe the “substantial” clinical impact of this research, highlighting evidence of a reduced risk of cirrhosis progression with metabolic surgery and the potential implications of these findings for liver transplant eligibility in patients who eventually reach decompensated cirrhosis but otherwise may not have been eligible for transplant due to their weight.

“As physicians, we're always trying to push boundaries and find the next best thing to help our patients,” Laique said.

Looking ahead to research she would like to see conducted in the future, Laique highlighted the need for studies assessing the safety and efficacy of metabolic surgery in patients with severe obesity who have cirrhosis and clinically significant portal hypertension; studies comparing medical therapies with surgical weight loss; and studies exploring metabolic surgery’s potential impact on cirrhosis regression.

Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. 

. March 14, 2024. Accessed February 3, 2025. 

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

Brooks A. Metabolic Surgery Improves Long-Term Liver Outcomes in MASH-Related Cirrhosis. 

. January 28, 2025. Accessed February 3, 2025. 

https://www.hcplive.com/view/metabolic-surgery-improves-long-term-liver-outcomes-mash-related-cirrhosis

Laique reviews data supporting the use of metabolic surgery in patients with obesity and cirrhotic MASH.

Addressing Unmet Needs in Cirrhotic MASH with Metabolic Surgery, with Sobia Laique, MD

In March 2024, resmetirom (Rezdiffra) made history when it became the first drug to earn US Food and Drug Administration approval for the treatment of 

, offering a long-awaited pharmacologic treatment option for a patient population once thought to be untreatable.

Despite its undeniable impact on the field of hepatology, the approval of resmetirom did not address the unmet needs faced by all patients with MASH. Indicated specifically for those with noncirrhotic MASH and moderate to advanced fibrosis, resmetirom is not currently approved for those with MASH and cirrhosis.

“The FDA’s approval of resmetirom as the first therapeutic agent for fibrotic, noncirrhotic MASH truly marked a significant milestone in the field,” Sobia Laique, MD, a gastroenterologist and transplant hepatologist at Cleveland Clinic, told 

. “However, we have to acknowledge there are considerable unmet clinical needs remaining, particularly for our patients with MASH-related cirrhosis, because we currently don't have any pharmacological therapies that are specifically approved to treat or reverse cirrhosis associated with MASH.”

In the absence of an FDA-approved drug for these patients, Laique described the different facets of disease management clinicians must be aware of, including optimizing behavioral health; lifestyle interventions; improving cardiometabolic health; mitigating risk factors for disease progression; and monitoring for complications of cirrhosis.

In patients with compensated cirrhosis, she emphasized the importance of preventing progression to decompensated cirrhosis, especially in patients with comorbid obesity.

“The added component of obesity itself increases their risk of decompensation annually by 3-fold, which is substantial,” Laique explained. “This highlights the critical need for obesity management in patients with compensated MASH cirrhosis.”

Recognizing the known impact metabolic surgery has on weight loss and the management of cardiometabolic comorbidities, she described its potential benefit for patients with obesity and compensated MASH cirrhosis and hypotheses about its ability to prevent major adverse liver outcomes (MALO) and hepatic decompensation, which were explored in the Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) study.

Indeed, results highlight a 72% reduced risk of incident MALO and an 80% reduced risk of progression to decompensation with metabolic surgery versus nonsurgical treatment in patients with compensated MASH-related cirrhosis and obesity.

Laique emphasizes the unmet needs for patients with cirrhotic MASH who are not eligible for resmetirom and what role metabolic surgery may play in their care.

Sobia Laique, MD

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