Liver and Bile
Lancet. 2023;401(10390):1786–97
Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicenter, open-label, randomized trial
Background: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomized trial.
Methods: The authors did a multicenter, open-label, randomized trial at 3 major hospitals in Rome, Italy. They included participants aged 25–70 years with obesity (BMI 30–55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. They randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary end point of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up.
Findings: Between April 15, 2019, and June 21, 2021, the authors biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. The authors randomly assigned 288 participants (67%) with biopsy-proven NASH to lifestyle modification plus best medical care (n = 96 [33%]), Roux-en-Y gastric bypass (n = 96 [33%]), or sleeve gastrectomy (n = 96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary end point was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p < 0.0001). The calculated probability of NASH resolution was 3.60 times greater (95% confidence interval [CI]: 2.19–5.92; p < 0.0001) in the Roux-en-Y gastric bypass group and 3.67 times greater (95% CI: 2.23–6.02; p < 0.0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per-protocol analysis (236 participants [82%] who completed the trial), the primary end point was met in 54 of 77 participants (70%) in the Roux-en-Y gastric bypass group and 55 of 79 participants (70%) in the sleeve gastrectomy group, compared with 15 of 80 (19%) in the lifestyle modification group (p < 0.0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in 10 participants (6%) who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management.
Interpretation: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimized medical therapy in the treatment of non-alcoholic steatohepatitis.