Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine.
School of Medicine & Holistic Integrative Medicine, Medical College of Nanjing University of Chinese Medicine.
Medicine (Baltimore). 2021 Mar 26;100(12):e24884. doi: 10.1097/MD.0000000000024884.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis.
Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed.
Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels.
Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.
非酒精性脂肪性肝病（NAFLD）是一种以肝细胞脂肪过度堆积为特征的高发慢性肝病。由于尚无药物获批用于 NAFLD 治疗，因此本项工作通过网络荟萃分析，研究了两种研究热点的药物（代谢靶点药物和天然植物药物）对 NAFLD 的作用。
检索截止至 2020 年 8 月 14 日的公共数据库，纳入比较奥贝胆酸、艾拉酚胺、塞尼可罗、塞尔西替尼、姜黄素、水飞蓟素和白藜芦醇与安慰剂的随机对照试验。分析肝脏病理改善、肝生化指标和脂质代谢指标。
共纳入 35 项荟萃分析研究。与安慰剂相比，奥贝胆酸可显著提高肝活检改善的频率（OR：2.10；95%CI：1.60，2.77）。肝生化指标的排序结果显示，奥贝胆酸（94.9%）和艾拉酚胺（86.3%）在降低丙氨酸氨基转移酶（ALT）水平方面具有相对优势，奥贝胆酸在降低天冬氨酸氨基转移酶（AST）水平方面也具有优势（95.4%）。考虑脂质代谢指标时，艾拉酚胺（expSMD：0.01；95%CI：0.00，0.05；SUCRA：100%）和奥贝胆酸（expSMD：0.48；95%CI：0.28，0.84；SUCRA：75.6%）均可显著降低 TG 水平；此外，奥贝胆酸而非艾拉酚胺可导致总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平显著升高和高密度脂蛋白胆固醇（HDL-C）水平降低。
新型代谢靶点药物通常比天然植物药物具有更好的效果，尤其是奥贝胆酸和艾拉酚胺。但是，奥贝胆酸会引起 LDL-C 水平升高和 HDL-C 水平降低等严重不良反应。姜黄素对 NAFLD 具有潜在优势，但缺乏统计学意义。
