Long-Term Study Reveals Benefits of Bariatric Surgery for Patients with MASH-Related Cirrhosis

A Cleveland Clinic study shows that patients with obesity and fatty liver-related cirrhosis who had bariatric surgery significantly lowered their future risk of developing serious liver complications compared with patients who received medical therapy alone. The results were published in Nature Medicine journal.

Ali Aminian, MD, director of Cleveland Clinic’s Bariatric & Metabolic Institute and lead investigator of the study, said results show that bariatric surgery should be considered as a treatment option in patients with cirrhosis and obesity. “Bariatric surgery was associated with a 72% lower risk of developing serious complications of liver disease and an 80% lower risk of progression to decompensated stage among patients with compensated cirrhosis and obesity.”

Obesity and diabetes are the leading causes of metabolic dysfunction-associated steatohepatitis (MASH), which is the most common form of chronic liver disease in the United States. Accumulation of fat within liver cells triggers a cascade of events ultimately leading to liver scarring. About 20% of people with MASH can progress to cirrhosis. Approximately three million people in the United States are estimated to have MASH-related cirrhosis.

“Patients with MASH-related cirrhosis have extremely limited treatment options. Currently, no therapeutic interventions have demonstrated efficacy in mitigating the risk of severe liver complications within this patient population,” said Sobia Laique, MD, a transplant hepatologist and the study coinvestigator at Cleveland Clinic. “This underscores a critical unmet need for the development of effective therapies specifically targeting patients with compensated MASH-related cirrhosis.”

Insights from a 15-year study

The aim of the SPECCIAL (Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term) study was to examine the long-term outcomes of bariatric surgery on the risk of developing major adverse liver outcomes (MALO) in patients with obesity and compensated MASH-related cirrhosis, compared with nonsurgical management. The study defined MALO as the first occurrence of ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma (HCC), liver transplantation or all-cause mortality.

A group of 62 Cleveland Clinic patients with compensated MASH-related cirrhosis and obesity who had bariatric surgery were compared with a control group of 106 nonsurgical patients and followed for 15 years. Study participants had similar characteristics such as severity of liver disease at their baseline liver biopsy.

Fifteen years after enrollment, study results show that 20.9% (95% confidence interval [CI], 2.5–35.9%) in the surgical group and 46.4% (95% CI, 25.6–61.3%) in the nonsurgical group developed MALO. The adjusted absolute risk difference of MALO was 22.1% (95% CI, 4.6–37.2%) favoring bariatric surgery, with an adjusted hazard ratio (HR) of 0.28 (95% CI, 0.12–0.64), P = .003.

Broken down by surgery type, the 15-year cumulative incidence of MALO was 20.1% (95% CI, 0.0–38.0%) after Roux-en-Y gastric bypass and 19.9% (95% CI, 0.0–42.0%) after sleeve gastrectomy.

Over the course of 15 years, 15.6% (95% CI, 0–31.3%) in the surgical group and 30.7% (95% CI, 12.9–44.8%) in the nonsurgical group progressed from compensated cirrhosis to the decompensated stage (adjusted absolute risk: 20.6% (95% CI, 3.7–35.2%); adjusted HR: 0.20 (95% CI, 0.06–0.68), P = .01). At 15 years, patients in the bariatric surgery group lost 26.6% (31.6 kg) of their weight and patients in the nonsurgical control group lost 9.8% (10.7 kg) of their weight.

A potential treatment option for a condition with few approved therapies

Steven Nissen, MD, Chief Academic Officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic and the study’s senior investigator, said: “Currently, lifestyle intervention is the only therapeutic recommendation for compensated MASH-related cirrhosis. However, lifestyle changes alone rarely provide the weight loss and metabolic changes needed to reduce the risk of liver complications in this patient population. The SPECCIAL study shows that bariatric surgery is an effective treatment that can influence the trajectory of cirrhosis progression in select patients.”

The authors note that the SPECCIAL study is the first to examine long-term clinical outcomes after bariatric surgery in patients with MASH-related cirrhosis. In 2021, the Cleveland Clinic-led SPLENDOR study suggested bariatric surgery as the first effective treatment for MASH without cirrhosis.

Future research is needed to study the new generation of anti-obesity medications and whether they can provide similar benefits in this patient population.