背景:非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)的晚期亚型。NASH患病率呈指数级增加,并且具有疾病进展的高风险,肝硬化,和肝脏相关的死亡率。Aldafermin,成纤维细胞生长因子19(FGF19)类似物,是不断发展的治疗剂之一,具有调节参与NASH发病机理的多种途径的潜力。我们旨在研究aldafermin在NASH患者中的疗效和安全性。
方法:PubMed,Scopus,科克伦图书馆,和WebofScience检索到2023年11月,以确定符合条件的随机对照试验(RCT)。连续数据汇总为平均差(MD),而二分数据合并为风险比(RR),95%置信区间.进行亚组荟萃分析以评估两种剂量(1mg和3mg)的aldafermin的疗效。
结果:纳入4个RCTs,共491名患者。Aldafermin显示肝脏脂肪含量降低≥30%的剂量依赖性改善(RR:2.16,95%CI[1.41,3.32])和(RR:5.00,95%CI[1.34,18.64]),丙氨酸氨基转移酶水平(MD:-19.79,95%CI[-30.28至-9.3])和(MD:-21.91,95%CI[-29.62至-14.21]),谷草转氨酶水平(MD:-11.79,95%CI[-18.06至-5.51])和(MD:-13.9,95%CI[-18.59至-9.21]),和增强的肝纤维化评分(ELF)(MD:-0.13,95%CI[-0.29至0.02])和(MD:-0.33,95%CI[-0.50至-0.17]),分别在1mg和3mg亚组中。在aldafermin组中没有检测到关于组织学终点的显著差异,血脂谱,代谢参数,和总体不利影响,除了aldafermin3mg亚组的腹泻发生率增加。
结论:Aldafermin是一种很有前途的耐受性良好的NASH治疗药物,有证据支持其降低肝脏脂肪含量的能力,纤维化血清生物标志物,和肝酶。然而,它在改善组织学纤维化方面的有效性,在显示数字趋势的同时,仍然缺乏统计学意义。有必要进行更大和更长的NASH试验,以增强证据的稳健性。
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of NASH. We aimed to investigate the efficacy and safety of aldafermin in patients with NASH.
METHODS: PubMed, Scopus, Cochrane Library, and Web of Science were searched till November 2023 to identify eligible randomized controlled trials (RCTs). Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses (1 mg and 3 mg) of aldafermin.
RESULTS: Four RCTs with a total of 491 patients were included. Aldafermin showed a dose-dependent improvement in the ≥30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: -19.79, 95 % CI [-30.28 to -9.3]) and (MD: -21.91, 95 % CI [-29.62 to -14.21]), aspartate aminotransferase levels (MD: -11.79, 95 % CI [-18.06 to -5.51]) and (MD: -13.9, 95 % CI [-18.59 to -9.21]), and enhanced liver fibrosis score (ELF) (MD: -0.13, 95 % CI [-0.29 to 0.02]) and (MD: -0.33, 95 % CI [-0.50 to -0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup.
CONCLUSIONS: Aldafermin is a promising well-tolerated therapeutic agent for NASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer NASH trials are warranted to enhance the robustness of the evidence.