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Abstract：
UNASSIGNED: Due to lack of targeted treatment options and inconsistent utilization of histologic endpoints among clinical trials, identifying efficacious pharmacotherapies for nonalcoholic steatohepatitis [NASH] has proven challenging.
UNASSIGNED: A thorough systematic review and frequentist random-effects network meta-analysis was performed across all randomized clinical trials reporting a pharmacotherapeutic intervention on biopsy-proven NASH. Primary outcomes were based on the most current, up-to-date recommended histologic endpoints.
UNASSIGNED: A total of 40 RCTs were identified including 6593 total patients. The most effective and statistically significant treatment interventions for minimum two-point improvement in NAFLD Activity Score were aldafermin 1 mg [RR 7.69, 95% CI 2.00; 29.57], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 3.38, 95% CI 1.88; 6.07], pioglitazone 45 mg [RR 3.29, 95% CI 1.74; 6.22], vitamin E 800 IU [RR 2.06, 95% CI 1.33; 3.18], resmetirom 80 mg [RR 1.74, 95% CI 1.03; 2.94], obeticholic acid 25 mg [RR 1.63, 95% CI 1.32; 2.01], and obeticholic acid 10 mg [RR 1.31, 95% CI 1.02; 1.67]). The most robust pharmacotherapies for NASH resolution without worsening fibrosis were found to be aldafermin 1 mg [RR 5.77, 95% CI 1.48; 22.51], pioglitazone 45 mg [RR 2.65, 95% CI 1.43; 4.91], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 2.64, 95% CI 1.36; 5.12], pioglitazone 30 mg [RR 2.46, 95% CI 1.56; 3.88], vitamin E 800 IU [RR 1.90, 95% CI 1.20; 3.00], and obeticholic acid 25 mg [RR 1.52, 95% CI 1.03; 2.23]). Obeticholic acid had a significant improvement on fibrosis. Multiple interventions were found to improve individual histologic scores across secondary outcome analyses and are detailed below.
UNASSIGNED: This novel systematic review and network meta-analysis represents the most comprehensive investigation to date regarding the pharmacotherapeutic options for biopsy-proven NASH using current recommended histologic endpoints.
UNASSIGNED: A thorough systematic review and frequentist random-effects network meta-analysis was performed across all randomized clinical trials reporting a pharmacotherapeutic intervention on biopsy-proven NASH. Primary outcomes were based on the most current, up-to-date recommended histologic endpoints.
UNASSIGNED: A total of 40 RCTs were identified including 6593 total patients. The most effective and statistically significant treatment interventions for minimum two-point improvement in NAFLD Activity Score were aldafermin 1 mg [RR 7.69, 95% CI 2.00; 29.57], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 3.38, 95% CI 1.88; 6.07], pioglitazone 45 mg [RR 3.29, 95% CI 1.74; 6.22], vitamin E 800 IU [RR 2.06, 95% CI 1.33; 3.18], resmetirom 80 mg [RR 1.74, 95% CI 1.03; 2.94], obeticholic acid 25 mg [RR 1.63, 95% CI 1.32; 2.01], and obeticholic acid 10 mg [RR 1.31, 95% CI 1.02; 1.67]). The most robust pharmacotherapies for NASH resolution without worsening fibrosis were found to be aldafermin 1 mg [RR 5.77, 95% CI 1.48; 22.51], pioglitazone 45 mg [RR 2.65, 95% CI 1.43; 4.91], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 2.64, 95% CI 1.36; 5.12], pioglitazone 30 mg [RR 2.46, 95% CI 1.56; 3.88], vitamin E 800 IU [RR 1.90, 95% CI 1.20; 3.00], and obeticholic acid 25 mg [RR 1.52, 95% CI 1.03; 2.23]). Obeticholic acid had a significant improvement on fibrosis. Multiple interventions were found to improve individual histologic scores across secondary outcome analyses and are detailed below.
UNASSIGNED: This novel systematic review and network meta-analysis represents the most comprehensive investigation to date regarding the pharmacotherapeutic options for biopsy-proven NASH using current recommended histologic endpoints.
摘要：
■由于临床试验中缺乏靶向治疗方案和对组织学终点的利用不一致，确定非酒精性脂肪性肝炎[NASH]的有效药物疗法已被证明具有挑战性。
■在所有报告对活检证实的NASH进行药物治疗干预的随机临床试验中，进行了全面的系统评价和频率随机效应网络荟萃分析。主要结果是基于最新的，最新的推荐组织学终点。
■共确定40个RCTs，包括6593名患者。NAFLD活动评分最低两点改善最有效且具有统计学意义的治疗干预措施为aldafermin1mg[RR7.69,95%CI2.00;29.57]，维生素E800IU联合吡格列酮45mg[RR3.38，95%CI1.88；6.07]，吡格列酮45mg[RR3.29，95%CI1.74；6.22]，维生素E800IU[RR2.06，95%CI1.33；3.18]，瑞美特罗姆80毫克[RR1.74，95%CI1.03；2.94]，奥贝胆酸25mg[RR1.63，95%CI1.32；2.01]，和奥贝胆酸10mg[RR1.31，95%CI1.02；1.67]）。发现对于NASH消退而不恶化纤维化的最稳健的药物疗法是aldafermin1mg[RR5.77,95%CI1.48;22.51],吡格列酮45毫克[RR2.65，95%CI1.43；4.91]，维生素E800IU联合吡格列酮45mg[RR2.64，95%CI1.36；5.12]，吡格列酮30毫克[RR2.46，95%CI1.56；3.88]，维生素E800IU[RR1.90，95%CI1.20；3.00]，和奥贝胆酸25mg[RR1.52，95%CI1.03；2.23]）。奥贝胆酸对纤维化有显著的改善作用。发现多种干预措施可改善次要结局分析中的个体组织学评分，详见下文。
■这项新颖的系统评价和网络荟萃分析代表了迄今为止使用当前推荐的组织学终点对活检证实的NASH的药物治疗选择的最全面的研究。
■在所有报告对活检证实的NASH进行药物治疗干预的随机临床试验中，进行了全面的系统评价和频率随机效应网络荟萃分析。主要结果是基于最新的，最新的推荐组织学终点。
■共确定40个RCTs，包括6593名患者。NAFLD活动评分最低两点改善最有效且具有统计学意义的治疗干预措施为aldafermin1mg[RR7.69,95%CI2.00;29.57]，维生素E800IU联合吡格列酮45mg[RR3.38，95%CI1.88；6.07]，吡格列酮45mg[RR3.29，95%CI1.74；6.22]，维生素E800IU[RR2.06，95%CI1.33；3.18]，瑞美特罗姆80毫克[RR1.74，95%CI1.03；2.94]，奥贝胆酸25mg[RR1.63，95%CI1.32；2.01]，和奥贝胆酸10mg[RR1.31，95%CI1.02；1.67]）。发现对于NASH消退而不恶化纤维化的最稳健的药物疗法是aldafermin1mg[RR5.77,95%CI1.48;22.51],吡格列酮45毫克[RR2.65，95%CI1.43；4.91]，维生素E800IU联合吡格列酮45mg[RR2.64，95%CI1.36；5.12]，吡格列酮30毫克[RR2.46，95%CI1.56；3.88]，维生素E800IU[RR1.90，95%CI1.20；3.00]，和奥贝胆酸25mg[RR1.52，95%CI1.03；2.23]）。奥贝胆酸对纤维化有显著的改善作用。发现多种干预措施可改善次要结局分析中的个体组织学评分，详见下文。
■这项新颖的系统评价和网络荟萃分析代表了迄今为止使用当前推荐的组织学终点对活检证实的NASH的药物治疗选择的最全面的研究。
