Abstract

Background:

Health agencies are waiting for studies with an extended follow-up evaluating whether resolution of MASH without worsening of fibrosis is associated with reduced risk of mortality. This study assessed the impact of histological evolution on long-term survival in MASH patients treated with bariatric surgery.

Methods: From 1994 to 2022, 2940 bariatric surgery candidates at CHU de Lille were prospectively included. Liver biopsy was performed systematically at baseline and a consecutive biopsy was proposed at one year for MASH patients. We studied in univariate and multivariate analysis the 15-year survival of baseline MASH and fibrosis as well as MASH resolution without worsening of fibrosis after surgery.

Results: At baseline, liver biopsy was available in 2687 (91%) patients, in whom 232 (8.6%) had biopsy-proven MASH. Paired biopsies before and 1 year after surgery were available in 146/232. Median follow-up of patients with biopsies was 14.7 years. At baseline, MASH patients were different than no-MASH patients for: age 47 vs 42 y, AST 37 vs 22 IU/L, GGT 56 vs 29 IU/L, glucose 133 vs 98 mg/dL, steatosis 60% vs 20% and fibrosis 2 vs 0 (p<0.001 for all), but not for BMI 45.8 vs 46.2 kg/m². At baseline, patients with MASH and patients with significant fibrosis (≥F2) had lower 15-year survival: 83.9% vs 92.7% p<0.001; 79.8% vs 94.0% p<0.001 respectively. After surgery, MASH resolution without worsening of fibrosis was associated with better biological and histological improvement in terms of steatosis 5% (1-20) vs 20% (10-40), fibrosis 1(0-2) vs 3(2-3), AST 21(18-27) vs 29(17-38) IU/L, GGT 22(14-33) vs 32(17-80) IU/L, glucose 93(86-108) vs 104(86-117) mg/dL (p<0.001 for all). MASH resolution was associated with a better 15-year survival in univariate analysis (88.4% vs. 70.8%, p=0.009) and multivariate analysis (HR 0.37, p=0.02) adjusted for age, gender, BMI, diabetes, arterial hypertension, dyslipidemia, and baseline fibrosis. Interestingly, 15-year survival of patients with MASH resolution became similar than those without baseline MASH: 88.4% vs 92.4%, p=0.4 (Figure). 95% of patient with fibrosis regression had MASH resolution. Those achieving a fibrosis regression to F0-F1 at 1 year had a better survival (87.5% vs 69.7% p < 0.01); however, it remained lower compared to baseline F0-F1 patients 95.2% vs 87.5% p=0.03.

Conclusion: Resolution of MASH without worsening of fibrosis is a predictive factor of long-term survival. Fibrosis regression was observed mainly after MASH resolution.