Billeter Adrian T, Reiners Beatrice, Seide Svenja E, Probst Pascal, Kalkum Eva, Rupp Christian, Müller-Stich Beat P
Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Hepatobiliary Surg Nutr. 2022 Oct;11(5):696-708. doi: 10.21037/hbsn-21-5.
Non-alcoholic steatohepatitis (NASH) comprises a major healthcare problem affecting up to 30% of patients with obesity and the associated risk for cardiovascular and liver-related mortality. Several new drugs for NASH-treatment are currently investigated. No study thus far directly compared surgical and non-surgical therapies for NASH. This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.
The study was conducted according to the PRISMA guidelines for network meta-analysis. PubMed, CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy. Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected. Patients with liver cirrhosis were excluded. Risk of bias was assessed with ROB-2 and ROBINS-I-tools. A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied. Main outcomes were NASH-resolution and improvement of fibrosis.
Out of 7,913 studies, twelve randomized non-surgical studies and twelve non-randomized surgical trials were included. NASH-resolution after non-surgical intervention was 29% [95% confidence interval (CI): 23-40%] and 79% (95% CI: 72-88%) after surgery. The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication [odds ratio (OR) =2.68; 95% CI: 1.44-4.97] while drug treatment was superior to placebo (OR =2.24; 95% CI: 1.55-3.24). Surgery (OR =2.18; 95% CI: 1.34-3.56) and medication (OR =1.79; 95% CI: 1.39-2.31) were equally effective to treat fibrosis compared to placebo without difference between them. The results did not change when only new drugs specifically developed for the treatment of NASH were included.
Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis. Trials directly comparing surgery with medication must be urgently conducted. Patients with NASH should be informed about surgical treatment options.
非酒精性脂肪性肝炎（NASH）是一个重大的医疗保健问题，影响着高达30%的肥胖患者，以及心血管疾病和肝脏相关死亡率的风险。目前正在研究几种用于治疗NASH的新药。迄今为止，尚无研究直接比较手术和非手术疗法对NASH的疗效。这项网状Meta分析首次使用一种新颖的统计方法比较了不同疗法对NASH的有效性。
本研究按照网状Meta分析的PRISMA指南进行。使用经过验证的检索策略，对PubMed、CENTRAL和科学网进行检索，不受时间或语言限制。选择在基线和至少12个月后进行肝活检的成人NASH治疗研究。排除肝硬化患者。使用ROB-2和ROBINS-I工具评估偏倚风险。应用一种新的人群调整间接比较方法，纳入并比较单臂试验。主要结局为NASH缓解和纤维化改善。
在7913项研究中，纳入了12项随机非手术研究和12项非随机手术试验。非手术干预后NASH缓解率为29%[95%置信区间（CI）：23%-40%]，手术后为79%（95%CI：72%-88%）。网状Meta分析表明，手术治疗NASH缓解的几率高于药物治疗[优势比（OR）=2.68；95%CI：1.44-4.97]，而药物治疗优于安慰剂（OR =2.24；95%CI：1.55-3.24）。与安慰剂相比，手术（OR =2.18；95%CI：1.34-3.56）和药物治疗（OR =1.79；95%CI：1.39-2.31）在治疗纤维化方面同样有效，两者之间无差异。仅纳入专门为治疗NASH开发的新药时，结果未改变。
代谢手术治疗NASH的效果优于药物治疗，而两者在改善纤维化方面同样有效。必须紧急开展直接比较手术和药物治疗的试验。应告知NASH患者手术治疗方案。
