Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
Aliment Pharmacol Ther. 2022 May;55(9):1076-1087. doi: 10.1111/apt.16808. Epub 2022 Mar 14.
Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs.
Medline, EMBASE and CENTRAL were searched for randomised controlled trials evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, at least 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and at least 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. Among 49 included trials, treatments modulating energy (Risk ratio (RR): 1.92, Credible intervals (Crl): 1.59-2.34) were most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.66, Crl: 0.65-4.50), bile acids (RR: 1.37, Crl: 0.99-1.92) and inflammation (RR: 1.00, Crl: 0.75-1.33). Energy and bile acids modulation were effective in at least 2-point NAS reduction without worsening of fibrosis (RR: 1.52, Crl 1.30-1.77; RR: 1.69, Crl 1.41-2.03) and at least 1-point reduction in fibrosis (RR: 1.26, Crl:1.05-1.49; RR: 1.54, Crl: 1.20-1.97).
This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.
非酒精性脂肪性肝炎（NASH）是最常见的肝脏疾病病因。然而，不同 NASH 药物类别的疗效比较缺乏。我们通过比较药物的组织学结果和靶点进行了一项网络荟萃分析，以评估药物类别。
我们在 Medline、EMBASE 和 CENTRAL 中检索了评估活检证实的 NASH 患者 NASH 药物的随机对照试验。主要结局包括无纤维化恶化的 NASH 缓解、至少 2 分的非酒精性脂肪性肝病活动评分（NAS）降低而纤维化无恶化以及至少 1 分的纤维化降低。治疗方法分为炎症、能量、胆汁酸和纤维化调节剂。该分析采用贝叶斯网络模型和累积排序曲线下面积（SUCRA）分析。在 49 项纳入的试验中，调节能量的治疗方法（风险比（RR）：1.92，可信区间（Crl）：1.59-2.34）最有可能实现 NASH 缓解，其次是调节纤维化的治疗方法（RR 1.66，Crl：0.65-4.50）、胆汁酸（RR：1.37，Crl：0.99-1.92）和炎症（RR：1.00，Crl：0.75-1.33）。能量和胆汁酸调节在至少 2 分的 NAS 降低而纤维化无恶化（RR：1.52，Crl 1.30-1.77；RR：1.69，Crl 1.41-2.03）和至少 1 分的纤维化降低（RR：1.26，Crl：1.05-1.49；RR：1.54，Crl：1.20-1.97）方面是有效的。
本网络分析表明，调节能量途径和胆汁酸的药物在 NASH 治疗中具有相对优势。这为联合治疗药物的开发和选择提供了指导。
