美国俄亥俄州克利夫兰诊所Steven E. Nissen团队研究了在经活检证实的非酒精性脂肪性肝炎患者中，减肥手术与重大不良肝脏和心血管结局的相关性。这一研究成果发表在2021年11月11日出版的《美国医学会杂志》上。

在非酒精性脂肪性肝炎（NASH）患者中，尚无治疗显示可降低严重不良结局的风险。该研究旨在探讨肥胖和活检证实无肝硬化的纤维性NASH患者的减肥手术与重大不良肝脏结局和重大不良心血管事件（MACE）之间的长期关系。

2004至2016年，美国卫生系统进行了25828次肝活检，确定1158名成年肥胖患者符合入选标准，包括确诊的NASH组织学诊断和肝纤维化（组织学1-3期）。采用重叠加权法，将在减肥手术时同时进行肝活检患者的基线临床特征、组织学疾病活动和纤维化分期与非手术对照组进行平衡。后续随访于2021年3月结束。

减肥手术包括Roux-en-Y胃分流术、袖状胃切除术，其他患者接受非手术护理。主要结局是重大不良肝脏结局（进展为临床或组织学肝硬化、发生肝细胞癌、肝移植或肝相关死亡率）和MACE（冠状动脉事件、脑血管事件、心力衰竭或心血管死亡的综合）的发生率。

1158名患者中740名（63.9%）为女性，中位年龄为49.8岁，中位体重指数为44.1。其中650名患者接受了减肥手术，508名患者接受了非手术对照护理，中位随访时间为7年。重叠加权后，基线协变量的分布（包括肝损伤的组织学严重程度）非常平衡。

在未加权数据集的研究期结束时，减肥手术组的5名患者和非手术对照组的40名患者出现了严重的肝脏不良反应，减肥手术组的39名患者和非手术组的60名患者出现了MACE。

在采用重叠加权法分析的患者中，减肥手术组10年重大不良肝脏结局的累积发生率为2.3%，显著低于非手术护理组的9.6%。减肥手术组和非手术护理组的10年MACE累积发生率分别为8.5%和15.7%，组间差异显著。在减肥手术后的第一年内，4名患者（0.6%）死于手术并发症，包括2例胃肠道渗漏和2例呼吸衰竭。

研究结果表明，在NASH和肥胖患者中，与非手术治疗相比，减肥手术可显著降低发生严重不良肝脏结局和MACE的风险。

附：英文原文

Title: Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis

Author: Ali Aminian, Abbas Al-Kurd, Rickesha Wilson, James Bena, Hana Fayazzadeh, Tavankit Singh, Vance L. Albaugh, Faiz U. Shariff, Noe A. Rodriguez, Jian Jin, Stacy A. Brethauer, Srinivasan Dasarathy, Naim Alkhouri, Philip R. Schauer, Arthur J. McCullough, Steven E. Nissen

Issue&Volume: 2021-11-11

Abstract:

Importance  No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH).

Objective  To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis.

Design, Setting, and Participants  In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021.

Exposures  Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care.

Main Outcomes and Measures  The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework.

Results  A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P=.01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P=.007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n=2) and respiratory failure (n=2).

Conclusions and Relevance  Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

DOI: 10.1001/jama.2021.19569

Source: https://jamanetwork.com/journals/jama/fullarticle/2786270