Bariatric Surgery Lowers Risk for Liver Complications in MASH

Among patients with obesity and compensated cirrhosis, bariatric surgery may significantly lower the risk of developing serious liver disease complications, according to a recent study by Cleveland Clinic researchers.

Compared with patients who received medical therapy alone, those who underwent bariatric surgery had a 72% lower risk of developing serious complications of liver disease and an 80% lower risk for progression to decompensated cirrhosis.

The results could have major implications for patients with metabolic dysfunction–associated steatohepatitis (MASH), particularly given that about 20% of patients with MASH progress to cirrhosis, the researchers said.

“Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis,” said Steven Nissen, MD, the senior author and chief academic officer of the Miller Family Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland.

“However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population,” he said. “This study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”

The study was published online in Nature Medicine.

Significantly Reduced Risks

As part of the Surgical Procedures Eliminate Compensated Cirrhosis in Advancing Long-Term (SPECCIAL) observational study, Nissen and colleagues compared the long-term effects of metabolic surgery and medical treatment in patients with obesity and compensated, biopsy-proven MASH-related cirrhosis. They looked for six major adverse liver outcomes (MALO): Ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and all-cause mortality.

Among nearly 37,000 patients who underwent liver biopsy at the Cleveland Clinic Health System between 1995 and 2020, the research team identified 168 patients (69.6% women) with MASH-related cirrhosis, Child-Pugh class A, and model for end-stage liver disease scores ≤10. Among those, 62 underwent metabolic surgery (37 Roux-en-Y gastric bypass and 25 sleeve gastrectomy) and 106 had nonsurgical treatment.

After overlap weighting, the groups had balanced baseline characteristics, including mean body mass index of 42.7, fibrosis-4 score of 2.1, albumin of 4.1 g/dL, bilirubin of 0.6 mg/dL, and Elixhauser comorbidity index of 9. In each group, 84.5% had type 2 diabetes and 79.1% had Ishak fibrosis stage 6.

Overall, the 15-year cumulative incidence of MALO was 20.9% in the surgical group and 46.4% in the nonsurgical group (adjusted hazard ratio [aHR], 0.28; P = .003), with MALO occurring in 10 surgical patients and 42 nonsurgical patients.

Assuming a causal effect, the number needed to treat with metabolic surgery to avoid one incidence of MALO over a 15-year timespan was 4.5. 

The 15-year incidence of MALO was similar between surgical methods, with 20.1% for Roux-en-Y gastric bypass and 19.9% for sleeve gastrectomy.

In addition, the 15-year cumulative incidence of progression to decompensated cirrhosis was 15.6% in the surgical group and 30.7% in the nonsurgical group (aHR, 0.2; P = .01), with decompensation occurring in four surgical patients and 33 nonsurgical patients.

At 15 years, patients in the surgical group lost 31.6 kg or about 26.6% of their weight, and those in the nonsurgical group lost 10.7 kg or 9.8%.

Among patients with type 2 diabetes at baseline, metabolic surgery was associated with a reduction in A1c levels, as well as diabetes remission for some patients.

Potential to Fill an Unmet Need

Previous studies have indicated that bariatric surgery can effectively treat noncirrhotic MASH and lead to histologic resolution of MASH. In a 2021 study, Nissen and colleagues found bariatric surgery was associated with a lower risk for MALO and major adverse cardiovascular events in patients with biopsy-proven MASH without cirrhosis. Now, Nissen said, the SPECCIAL study indicates surgery may be a good option for MASH-related cirrhosis as well.

The study authors also noted that similar findings are theoretically possible from medical therapies, given the emergence of a new generation of anti-obesity medications. In this study, 16.8% of the surgical group and 14.3% of the nonsurgical group took semaglutide or tirzepatide at some point during the follow-up period.

“Patients with MASH-related cirrhosis have extremely limited treatment options,” said Sobia Laique, MD, study co-author and a transplant hepatologist at the Cleveland Clinic, Cleveland, who specializes in MASH-related cirrhosis. She co-founded the Cleveland Clinic’s task force on metabolic dysfunction–associated steatotic liver disease (MASLD) to improve screening, management, and patient outcomes for MASLD and related comorbidities.

“No therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications for these patients,” she said. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”

No funding was reported for this study. Several authors reported receiving grant funding, consultant fees, and advisory roles for various pharmaceutical companies.

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape Medical News, MDedge, and WebMD.