MASH resolution without worsening fibrosis boosts 15-year survival after bariatric surgery

Key takeaways:

• Patients with MASH and significant fibrosis at baseline had lower 15-year survival.
• Survival of patients with MASH resolution was similar to those without baseline MASH.

BOSTON — Resolution of metabolic dysfunction-associated steatohepatitis without worsening of fibrosis was linked to long-term survival after bariatric surgery, similar to that of patients without baseline MASH, according to a presenter.

“The FDA and experts have endorsed the resolution of MASH without worsening of fibrosis or improvement in fibrosis as acceptable surrogate endpoints to assess the prevention of cirrhosis and liver-related mortality,” Guillaume Lassailly, MD, PhD, of the University of Lille in France, said during his presentation at The Liver Meeting. “However, their significance in the natural history of MASH, their link with mortality and their use in the context of MASH treatment, metabolic syndrome and, therefore, bariatric surgery are warranted.”

To examine the effects of histological progression of MASH and fibrosis on long-term survival in patients who underwent bariatric surgery, Lassailly and colleagues assessed 3,028 adults in the Lille bariatric cohort from 1994 to 2022. All patients underwent liver biopsy at baseline, with consecutive biopsies performed at 1 and 5 years for those with MASH and fibrosis.

According to Lassailly, 2,682 patients were included at baseline, of whom 232 had biopsy-proven MASH and 267 had stage F2 to F4 fibrosis. One-year follow-up data was available for 2,522 patients, of whom 746 had consecutive liver biopsies. In this population, 732 patients had available MASH status and 594 had suitable biopsy quality to assess MASH and fibrosis.

The study’s primary outcome was impact of MASH resolution without worsening of fibrosis on 15-year survival, while secondary outcomes included MASH resolution, regardless of fibrosis, and the effect of fibrosis improvement from stage F2 to F4 to F0 to F1 on 15-year survival.

According to results, MASH at baseline was significantly associated with lower 15-year survival (83.9% vs. 92.7%), as was fibrosis of at least stage F2 (79.8% vs. 94%). However, MASH resolution without worsening of fibrosis improved 15-year survival (88.4% vs. 70.8%; HR = 3.84; 95% CI, 1.06-13.9), similar to that of patients without baseline MASH (88.4% vs. 92.4%).

Further, after adjusting for age, gender, diabetes, hypertension, dyslipidemia and baseline fibrosis, the persistence of MASH or worsening of fibrosis increased mortality by 2.54.

Results also showed that MASH resolution, regardless of fibrosis, occurred in about 80% of the cohort, and improvement of fibrosis from stage F2 to F4 to F0 to F1 correlated with longer 15-year survival; however, there was no statistical difference between the group without fibrosis and the one with improvement of fibrosis (HR = 2.04; 95% CI, 0.58-7.22).

“This is the first study to show that resolution of MASH with no worsening of fibrosis is a reliable surrogate endpoint in the context of bariatric surgery,” Lassailly said. “For fibrosis progression, our data suggest that a survival benefit could be obtained only after a significant reduction in liver fibrosis, reaching mild fibrosis stage.”