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他汀类药物在治疗和发展非酒精性脂肪性肝病和脂肪性肝炎中的疗效:系统评价和荟萃分析。

Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis.

机构信息

Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.

Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.

出版信息

Clin Res Hepatol Gastroenterol. 2022 Apr;46(4):101816. doi: 10.1016/j.clinre.2021.101816. Epub 2021 Oct 2.


DOI:10.1016/j.clinre.2021.101816
PMID:34607067
Abstract

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown. PURPOSE: We conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD. METHODS: Electronic databases (MEDLINE and Cochrane CENTRAL) were searched from their inception until May 2021 for observational studies and randomized controlled trials (RCTs) that assessed the efficacy of statins for the treatment of NAFLD and its development. Studies were included irrespective of the dosage or duration, and their risk of bias was assessed. The outcomes of interest for our study were the effect of statins on liver histology (steatosis, fibrosis and necroinflammation, NAFLD activity score [NAS]) and liver enzymes (Alanine transaminase [ALT], Aspartate transaminase [AST], and Gamma-glutamyl transferase [GGT] levels). To pool continuous outcomes, a random-effects model was used to derive weighted mean difference (WMD) or standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs). Generic inverse variance was then used for different measurement units reported by the studies. For studies investigating the effects of statins on the development of NAFLD, generic inverse variance along with random effects model was used to derive odds ratio (ORs) and its corresponding 95% confidence interval (CI). RESULTS: A total of 14 studies including 1,247,503 participants were short-listed for our analysis. All the studies included in our analysis had a low to moderate risk of bias. The results of our analysis suggest that statins may significantly reduce the risk of developing NAFLD (OR:0.69, 95% CI [0.57,0.84]; p = 0.0002; I² =36%). Statin use significantly reduced ALT levels (WMD: -27.28, 95% CI [-43.06, -11.51]; p = 0.0007; I² =90%), AST levels (WMD: -10.99, 95% CI [-18.17, -3.81]; p = 0.003; I² =79%) and GGT levels (WMD: -23.40, 95% CI [-31.82, -14.98]; p < 0.00001; I² = 21%) in patients presenting with NAFLD at baseline. In liver histology outcomes, steatosis grade (SMD: -2.59, 95% CI [-4.61, -0.56]; p = 0.01; I² = 95%), NAS (WMD: -1.03, 95% CI [-1.33, -0.74]; p < 0.00001; I² = 33%), necro-inflammatory stage (WMD: -0.19, 95% CI [-0.26, -0.13]; p < 0.00001; I² = 0%) and significant fibrosis (OR:0.20, 95% CI [0.04, 0.95]; p = 0.04; I² = 97%) underwent notable reduction. However, fibrosis stage outcome (WMD: 0.07, 95% CI [-0.05, 0.20]; p = 0.27; I² = 0%) was non-significant. CONCLUSION: There was a significant decrease in transaminase and transferase levels. Marked improvement in liver histology of NAFLD patients was observed. Statin use also remarkably reduced the risk of developing NAFLD. Future large-scale trials can further aid in identifying the positive impact of statins in treatment for NAFLD and those at risk of developing it.

摘要

背景:非酒精性脂肪性肝病 (NAFLD) 是全球最常见的慢性肝病病因之一。目前,NAFLD 尚无普遍接受的有效治疗方法。虽然各种研究表明他汀类药物可有效降低肝酶并改善肝组织学,但它们在治疗和发展 NAFLD 方面的功效仍不清楚。

目的:我们进行了这项荟萃分析,以评估他汀类药物在治疗和发展 NAFLD 中的疗效。

方法:从电子数据库 (MEDLINE 和 Cochrane CENTRAL) 中检索了从成立到 2021 年 5 月的观察性研究和随机对照试验 (RCT),评估了他汀类药物治疗 NAFLD 及其发展的疗效。无论剂量或持续时间如何,均纳入了这些研究,并对其偏倚风险进行了评估。我们研究的主要结局是他汀类药物对肝组织学 (脂肪变性、纤维化和坏死性炎症、NAFLD 活动评分 [NAS]) 和肝酶 (丙氨酸氨基转移酶 [ALT]、天冬氨酸氨基转移酶 [AST] 和γ-谷氨酰转移酶 [GGT] 水平) 的影响。为了汇总连续结局,使用随机效应模型得出加权均数差 (WMD) 或标准化均数差 (SMD) 及其相应的 95%置信区间 (CI)。对于研究报告的不同测量单位,使用通用逆方差。对于研究他汀类药物对 NAFLD 发展影响的研究,使用通用逆方差和随机效应模型得出比值比 (OR) 及其相应的 95%置信区间 (CI)。

结果:共筛选出 14 项研究,包括 1247503 名参与者。我们分析中纳入的所有研究均具有低至中度的偏倚风险。分析结果表明,他汀类药物可能显著降低 NAFLD 的发病风险 (OR:0.69, 95% CI [0.57,0.84]; p=0.0002; I²=36%)。他汀类药物治疗可显著降低 ALT 水平 (WMD:-27.28, 95% CI [-43.06, -11.51]; p=0.0007; I²=90%)、AST 水平 (WMD:-10.99, 95% CI [-18.17, -3.81]; p=0.003; I²=79%) 和 GGT 水平 (WMD:-23.40, 95% CI [-31.82, -14.98]; p<0.00001; I²=21%),基线时患有 NAFLD 的患者。在肝组织学结局方面,脂肪变性程度评分 (SMD:-2.59, 95% CI [-4.61, -0.56]; p=0.01; I²=95%)、NAS (WMD:-1.03, 95% CI [-1.33, -0.74]; p<0.00001; I²=33%)、坏死性炎症分期 (WMD:-0.19, 95% CI [-0.26, -0.13]; p<0.00001; I²=0%) 和显著纤维化 (OR:0.20, 95% CI [0.04, 0.95]; p=0.04; I²=97%) 显著降低。然而,纤维化程度评分结局 (WMD:0.07, 95% CI [-0.05, 0.20]; p=0.27; I²=0%) 无显著差异。

结论:肝酶和转移酶水平显著降低。NAFLD 患者的肝组织学显著改善。他汀类药物治疗还显著降低了 NAFLD 的发病风险。未来的大规模试验可以进一步帮助确定他汀类药物在治疗 NAFLD 和那些有发病风险的患者中的积极作用。

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