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 randomised trial. We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25–70 years with obesity (BMI 30–55 kg/m), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at , . Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants 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 endpoint 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% CI 2·19–5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (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 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.

中文翻译：

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减肥代谢手术与生活方式干预加最佳医疗护理治疗非酒精性脂肪性肝炎 (BRAVES)：一项多中心、开放标签、随机试验

观察性研究表明，减肥代谢手术可能会大大改善非酒精性脂肪性肝炎（NASH）。然而，尚未在随机试验中将手术治疗 NASH 的疗效与生活方式干预和药物治疗的效果进行比较。我们在意大利罗马的三家主要医院进行了一项多中心、开放标签、随机试验。我们纳入了年龄 25-70 岁、肥胖（BMI 30-55 kg/m）、患有或不患有 2 型糖尿病、经组织学证实患有 NASH 的参与者。我们随机分配（1:1:1）参与者接受生活方式改变加上最佳医疗护理、Roux-en-Y 胃绕道手术或袖状胃切除术。该研究的主要终点是 1 年随访时 NASH 的组织学消退且纤维化未恶化。这项研究注册于，。2019年4月15日至2021年6月21日期间，我们对431名参与者进行了活检筛查；其中，103 人 (24%) 没有组织学 NASH，40 人 (9%) 拒绝参加。我们将 288 名 (67%) 经活检证实患有 NASH 的参与者随机分配到生活方式改变加最佳医疗护理 (n=96 [33%])、Roux-en-Y 胃绕道手术 (n=96 [33%]) 或袖套治疗组胃切除术（n=96 [33%]）。在意向治疗分析中，Roux-en-Y 胃绕道手术组 (54 [56%]) 和袖状胃切除术组 (55 [57%]) 达到主要终点的参与者百分比显着更高改变生活方式（15 [16%]；p<0·0001）。Roux-en-Y 胃绕道组中 NASH 解决的计算概率高出 3·60 倍（95% CI 2·19–5·92；p<0·0001），高出 3·67 倍（2·23 –6·02；p<0·0001) 袖状胃切除术组与生活方式改变组相比。在每个方案分析中（完成试验的 236 名参与者 [82%]），Roux-en-Y 胃绕道组的 77 名参与者中有 54 名（70%）达到了主要终点，79 名参与者中有 55 名（70%）达到了主要终点。袖状胃切除术组有 80 名参与者，而生活方式改变组有 15 名参与者 (19%) (p<0·0001)。本研究中没有报告死亡或危及生命的并发症。十名 (6%) 接受减肥代谢手术的参与者发生了严重不良事件，但这些参与者不需要再次手术，并且严重不良事件通过药物或内窥镜治疗得到解决。在治疗 NASH 方面，减肥代谢手术比生活方式干预和优化药物治疗更有效。Fondazione Policlinico Universitario A Gemelli、Policlinico Universitario Umberto I 和 S Camillo 医院，罗马，意大利。