Metabolic surgery may reverse MASH cirrhosis

Researchers at Cleveland Clinic have demonstrated that metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis regression can occur following metabolic and bariatric surgery (MBS). The study, “Can Metabolic Surgery Regress MASH Cirrhosis? Evidence From Paired Biopsies,” was presented at the 2026 Digestive Disease Week Annual Meeting.

In a retrospective cohort of patients with biopsy-proven compensated MASH cirrhosis undergoing MBS, investigators evaluated long-term outcomes using paired liver biopsies obtained at the time of surgery and at follow-up. Among 30 patients with a median follow-up of more than six years, cirrhosis regression, defined as improvement to a less advanced stage of fibrosis, was observed in one-third of patients.

“These findings challenge the long-held view that cirrhosis is a fixed, end-stage condition,” said Dr Sobia Laique, Director of the Multidisciplinary MASLD Center. “In selected patients, sustained metabolic intervention can lead to meaningful structural improvement in the liver.”

These findings build on prior work from the same investigative team demonstrating that MBS alters the clinical trajectory of MASH cirrhosis. In the SPECCIAL study, ‘Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis’, published in Nature Medicine, MBS was associated with a 72% reduction in major adverse liver outcomes, including liver transplantation, liver cancer, and liver-related death, and an 80% reduction in hepatic decompensation compared with nonsurgical management.

“These findings showed clear clinical benefit,” added Dr Ali Aminian, Director of the Bariatric and Metabolic Institute and senior author on the study. “This study helps contextualise those outcomes, suggesting that regression of cirrhosis may be occurring in a subset of patients.”

In addition to cirrhosis regression, patients showed marked improvement in steatohepatitis, including reduced fat accumulation and liver inflammation, reflecting improvement in the underlying disease process driving progression to hepatic decompensation. Importantly, the extent of observed cirrhosis regression varied by assessment method. Using the NASH Clinical Research Network (CRN) staging system, cirrhosis regression was identified in one-third of patients.

In contrast, alternative approaches that better capture regression within cirrhosis, such as the Beijing classification, suggested higher rates, with regressive features observed in up to 60% of patients. This suggests that traditional stage-based systems may underestimate the extent of recovery following metabolic intervention. Exploratory analyses further suggested that greater weight loss was associated with regressive features when assessed using these approaches, underscoring the importance of how fibrosis remodelling is measured.

Taken together, these findings suggest that MASH cirrhosis may be a dynamic, modifiable disease rather than an irreversible endpoint. Given the limited efficacy of current pharmacologic therapies in compensated MASH cirrhosis, these data support MBS as a disease-modifying strategy in carefully selected patients.

The group has established a dedicated metabolic biorepository, comprising patient tissue and biospecimens, to better define the biological mechanisms underlying cirrhosis regression following MBS and to identify predictors of treatment response. Separately, planned studies include a head-to-head comparison of MBS and GLP-1–based therapy in patients with MASH cirrhosis, as well as expansion of surgical strategies in patients with compensated cirrhosis and oesophageal varices, including evaluation of staged approaches such as transjugular intrahepatic portosystemic shunt followed by sleeve gastrectomy.

The inaugural Cleveland Clinic Multidisciplinary MASH Conference 2026 will be held in August 2026, bringing together experts across specialties to address the full spectrum of MASH and advance multidisciplinary care. For more information, please click here