Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, China.
Drugs. 2024 Apr;84(4):425-439. doi: 10.1007/s40265-024-02015-6. Epub 2024 Mar 13.
Nonalcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects approximately 38% of the world's population, yet no pharmacological therapies have been approved for treatment. We conducted a traditional and network meta-analysis to comprehensively assess the effectiveness of drug regimens on NAFLD, and continued to use the old terminology for consistency.
Randomized, placebo-controlled trials (RCTs) investigating drug therapy in an adult population diagnosed with NAFLD with or without diabetes mellitus were included. We assessed the quality of RCTs via the Risk of Bias 2 (ROB 2) tool. When I < 50%, we chose a random-effects model, otherwise a fixed-effects model was selected. A random effects model was applied in the network meta-analysis. The odds ratio (OR), weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence interval (CI) were used for outcome evaluation. The primary endpoint was the resolution of nonalcoholic steatohepatitis (NASH) without the worsening of liver fibrosis. Other endpoints included histological findings and metabolic changes. The PROSPERO Registration ID was CRD42023404309.
Thiazolidinediones (TZDs), vitamin E plus pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists and fibroblast growth factor-21 (FGF-21) analogue had a higher surface under the cumulative ranking curve (SUCRA = 76.6, 73.0, 72.0 and 71.6) regarding NASH resolution. Improvement of liver fibrosis stage (≥ 1) was observed with obeticholic acid 25 mg/day (OR 2.01, 95% CI 1.35-2.98), lanifibranor 1200 mg/day (OR 2.39, 95% CI 1.19-4.82) and silymarin (OR 4.54, 95% CI 1.18-17.43) in traditional meta-analysis.
The results of the comprehensive analysis suggested hypoglycemic drug therapy as an effective intervention for NAFLD, with or without diabetes mellitus. A prioritized selection of TZDs, vitamin E plus pioglitazone, GLP-1 receptor agonists and FGF-21 analogue may be considered for NASH resolution. Obeticholic acid, lanifibranor and silymarin could be considered for the improvement of liver fibrosis. Each medication was relatively safe compared with placebo.
非酒精性脂肪性肝病（NAFLD），目前被称为代谢功能障碍相关脂肪性肝病（MASLD），影响着全球约 38%的人口，但目前尚无批准用于治疗的药物。我们进行了一项传统和网络荟萃分析，以全面评估药物治疗方案对 NAFLD 的疗效，并为保持一致性继续使用旧术语。
纳入了评估在患有或不患有糖尿病的 NAFLD 成人患者中使用药物治疗的随机、安慰剂对照试验（RCT）。我们使用风险偏倚 2 工具（ROB 2）评估 RCT 的质量。当 I² < 50%时，我们选择随机效应模型，否则选择固定效应模型。在网络荟萃分析中应用随机效应模型。使用比值比（OR）、加权均数差（WMD）或标准均数差（SMD）及其 95%置信区间（CI）进行结局评估。主要终点是不伴有肝纤维化恶化的非酒精性脂肪性肝炎（NASH）缓解。其他终点包括组织学发现和代谢变化。PROSPERO 注册号为 CRD42023404309。
噻唑烷二酮类（TZDs）、维生素 E 加吡格列酮、胰高血糖素样肽-1（GLP-1）受体激动剂和成纤维细胞生长因子-21（FGF-21）类似物在 NASH 缓解方面的累积排序曲线下面积（SUCRA=76.6、73.0、72.0 和 71.6）更高。熊去氧胆酸 25 mg/天（OR 2.01，95%CI 1.35-2.98）、拉尼非尼 1200 mg/天（OR 2.39，95%CI 1.19-4.82）和水飞蓟宾（OR 4.54，95%CI 1.18-17.43）可改善≥1 级肝纤维化阶段。
综合分析结果表明，降糖药物治疗对合并或不合并糖尿病的 NAFLD 是一种有效的干预措施。对于 NASH 缓解，可优先选择 TZDs、维生素 E 加吡格列酮、GLP-1 受体激动剂和 FGF-21 类似物。熊去氧胆酸、拉尼非尼和水飞蓟宾可用于改善肝纤维化。与安慰剂相比，每种药物的安全性都相对较好。
