英国伦敦国王学院Geltrude Mingrone团队比较了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的疗效。2023年4月20日，该研究成果发表在《柳叶刀》杂志上。

观察性研究表明，减肥代谢手术可能极大地改善非酒精性脂肪性肝炎（NASH）。然而，在一项随机试验中，手术治疗NASH的疗效尚未与生活方式干预和药物治疗的效果进行比较。

研究组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，纳入年龄在25~70岁的肥胖（BMI 30-55 kg/m²）、患或不患2型糖尿病、经组织学证实患有NASH的参与者。将参与者随机分配（1:1:1）进行生活方式改变加最佳医疗护理、Roux-en-Y胃旁路术或袖状胃切除术。该研究的主要终点是在1年的随访中，NASH的组织学消退而没有纤维化恶化。

2019年4月15日至2021年6月21日，研究组对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%）拒绝参与。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胃旁路术（n=96[%3]）或袖状胃切除术（n=96 33%]）。

在意向治疗分析中，Roux-en-Y胃旁路术组（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著高于生活方式改变组（15[16%]）。与生活方式改变组相比，Roux-en-Y胃旁路术组NASH消退的计算概率高出3.60倍（p＜0.0001），袖状胃切除术组NASH消退的计算概率为3.67倍（p＞0.0001）。

在按方案分析中（完成试验的236名[82%]参与者），Roux-en-Y胃旁路术组77名参与者中有54名（70%）、袖状胃切除术组79名参与者中55名（70%）达到了主要终点，而生活方式改变组80名参与者中只有15名（19%，p<0.0001）。研究未报告死亡或危及生命的并发症。10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，严重不良事件通过医疗或内镜治疗得以解决。

研究结果表明，在NASH的治疗中，减肥代谢手术比生活方式干预和优化的药物治疗更有效。

附：英文原文

Title: Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial

Author: Ornella Verrastro, Simona Panunzi, Lidia Castagneto-Gissey, Andrea De Gaetano, Erminia Lembo, Esmeralda Capristo, Caterina Guidone, Giulia Angelini, Francesco Pennestrì, Luca Sessa, Fabio Maria Vecchio, Laura Riccardi, Maria Assunta Zocco, Ivo Boskoski, James R Casella-Mariolo, Pierluigi Marini, Maurizio Pompili, Giovanni Casella, Enrico Fiori, Francesco Rubino, Stefan R Bornstein, Marco Raffaelli, Geltrude Mingrone

Issue&Volume: 2023-04-20

Abstract:

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 randomised trial.

Methods

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/m2), 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 ClinicalTrials.gov, NCT03524365.

Findings

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.

Interpretation

Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH.

DOI: 10.1016/S0140-6736(23)00634-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00634-7/fulltext