Nonalcoholic Steatohepatitis Is Associated With Increased Mortality in Obese Patients Undergoing Bariatric Surgery.
Nonalcoholic Steatohepatitis Is Associated With Increased Mortality in Obese Patients Undergoing Bariatric Surgery.
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DOI：
10.1016/j.cgh.2015.10.010
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发表时间：
2016-11
期刊：
影响因子：
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通讯作者：
Giostra E
中科院分区：
文献类型：
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作者：
Goossens N;Hoshida Y;Song WM;Jung M;Morel P;Nakagawa S;Zhang B;Frossard JL;Spahr L;Friedman SL;Negro F;Rubbia-Brandt L;Giostra E
减肥手术可改善重度肥胖患者的预后。我们研究了非酒精性脂肪性肝炎（NASH）与接受减肥手术患者肝脏基因表达模式的预后相关性。我们对1997年1月至2004年12月在瑞士的一个中心接受胃旁路减肥手术的492名受试者进行了回顾性分析；收集常规围手术期肝活检，进行组织学分析，并分离RNA。我们收集了总生存率、临床和生化参数的数据，并将这些数据与参加第三次全国健康与营养检查调查（NHANES III）的倾向评分匹配受试者的数据进行了比较。我们使用肝脏活检来识别患有NASH的减肥手术患者；NHANES III型NASH患者是根据肝脏超声高回声和谷丙转氨酶水平升高来确定的。我们分析了47例减肥手术NASH患者肝组织中与NAFLD严重程度相关的32个基因特征，并使用最近模板预测和生存分析评估其预后特征。基线时，接受减肥手术患者的中位体重指数为43.6 kg/m2；根据组织学结果，12%的患者有NASH， 16%的患者有纤维化。在手术后平均10.2年的随访中，4.2%的受试者死亡。在多变量Cox回归中，NASH（风险比[HR]， 2.9； P= 0.02）和动脉高血压（风险比[HR]， 3.9； P= 0.02）的存在与总死亡率相关。当减肥手术患者与NHANES III参与者匹配时，减肥手术降低了随访期间的死亡风险（HR, 0.54； P= 0.04）。然而，与患有NASH的NHANES III参与者相比，减肥手术患者的死亡风险并没有降低（HR, 0.90； P= 0.85）。在多变量分析中，我们在NASH患者的肝组织中发现了与死亡风险增加相关的32个基因的表达模式（HR, 7.7； P= 0.045）。在减肥手术后10.2年的中位随访中，组织学证实的NASH与未接受减肥手术的患者相比，死亡风险增加有关。对NASH患者进行减肥手术的生存率可能会降低。32个基因表达模式确定了接受减肥手术且生存时间较短的NASH患者。
Bariatric surgery is associated with improved outcomes in subjects with severe obesity. We investigated the prognostic relevance of non-alcoholic steatohepatitis (NASH) and liver gene expression patterns in patients undergoing bariatric surgery. We performed a retrospective analysis of 492 subjects who underwent gastric bypass bariatric surgery at a single center in Switzerland from January 1997 through December 2004; routine peri-operative liver biopsies were collected, analyzed histologically, and RNA was isolated. We collected data on overall survival and clinical and biochemical parameters and compared these with data from propensity score-matched subjects participating in the third National Health and Nutrition Examination Survey (NHANES III). We used liver biopsies to identify bariatric surgery patients with NASH; NHANES III participants with NASH were identified based on a hyperechogenic liver at ultrasound and increased alanine transaminase levels. We analyzed a 32-gene signature associated with NAFLD severity in the liver tissues collected from 47 bariatric surgery patients with NASH, and assessed its prognostic features using nearest template prediction and survival analysis. At baseline, the median body mass index of patients who underwent bariatric surgery was 43.6 kg/m2; based on histologic findings, 12% had NASH and 16% had fibrosis. During a median follow-up of 10.2 years after the surgery, 4.2% of the subjects died. In multivariable Cox regression, the presence of NASH (hazard ratio [HR], 2.9; P=.02) and arterial hypertension (HR, 3.9; P=.02) were associated with overall mortality. When bariatric surgery patients were matched with NHANES III participants, bariatric surgery reduced the risk of death during the follow-up period (HR, 0.54; P=.04). However, bariatric surgery patients with NASH did not have a reduced risk of death compared to NHANES III participants with NASH (HR, 0.90; P=.85). We identified an expression pattern of 32 genes in liver tissues from patients with NASH that was associated with increased risk of death in multivariable analysis (HR, 7.7; P=.045). Histologically proven NASH is associated with increased risk of death within a median follow-up of 10.2 years after bariatric surgery, compared to patients who undergo bariatric surgery without NASH. The survival benefit of bariatric surgery in subjects with NASH may be reduced. A 32-gene expression pattern identified NASH patients who underwent bariatric surgery and had shorter survival times.