| 摘要: | 背景
非酒精性脂肪性肝病（NAFLD）是一般人群中最常見的肝臟疾病。 NAFLD與心血管病死率和發病率增加有關，心血管疾病是NAFLD患者死亡的主要原因。尚無有效的治療方法，指南也未建議使用藥物。最近的報告顯示，在NAFLD患者中使用他汀類藥物可能會降低心血管風險，並防止他們出現心血管事件。這是否是一致的效果或是否可以改善心血管結果尚不清楚。
目標
為了盡可能多地發現和總結現有的他汀類藥物對NAFLD患者心血管病死率和發病率的證據，然後根據發現數據得出他汀類藥物是否可以減少NAFLD患者心血管事件的最終結論。
搜索方法
截至2019年1月，我們在PubMed，Embase，Web of science，clinicaltrial.gov，sciencedirect.com，Cochrane圖書館進行了計算機化文獻檢索。我們對出版語言或出版日期沒有任何限制。
選擇標準
所有使用他汀類藥物治療NAFLD與未治療，安慰劑或其他降血脂藥物和納入研究的隨機臨床試驗和觀察性研究必須對參與者的心血管結果進行評估。參與者被診斷患有NAFLD或NAFLD的替代標誌物升高。
數據收集和分析
納入論文必須由兩位作者進行篩?和選擇。提取數據，兩位評價作者獨立評估每項試驗的偏倚風險。盡可能進行Meta分析。使用了Review Manager 5.2。
主要結果
當使用所描述的搜索方法並且應用搜索結果的資格標準時，發現了877個記錄。其中只有3項是隨機臨床試驗的事後分析和1項被認為符合納入標準的隊列研究。總人口為4329人。
我們將所有研究評估為高度偏倚風險。三項事後分析來自開放標籤隨機對照試驗，回顧性隊列研究的可比性不可靠。
僅在一項隊列研究中報告了關於心血管死亡率的數據，並且2個研究組之間的差異沒有統計學意義，aHR = 1.2（95％CI：0.26-5.54）有利於沒有藥物治療組。在3項事後分析中評估了一致的心血管疾病發病率，即在較高劑量或更強化治療的他汀類藥物可使研究人群心血管事件相對風險降低44％至68％。與安慰劑或中度他汀類藥物組相比，在更強的他汀類藥物組中觀察到肝功能檢查以及脂質譜的統計學顯著改善。較高劑量的阿托伐他汀顯著降低了NAFLD的存在。與使用阿托伐他汀24mg /天的組相比，阿托伐他汀組34mg /天的NAFLD分辨率更高（86％對74％; p = 0.0012）。
作者的結論
根據該評價的結果，其中包括四項具有高偏倚風險和少數參與者的研究，他汀類藥物可能改善血清肝?和血脂水平以及堅定的NAFLD。
就心血管結果而言，我們無法得出關於他汀類藥物對NAFLD患者的益處的確定結論。然而，更強的他汀類藥物治療可降低NAFLD高風險患者（肝功能檢查異常或ALT水平升高）的心血管疾病發病率。
Background
Non-alcoholic fatty liver disease (NAFLD) is the most popular liver disease in the world. NAFLD has been well evidenced to associate with cardiovascular (CV) fatality and morbidity. It appears that cardiovascular complications are the main reason of death in this population. No effective treatment is yet available as well as no medication use was recommended by guidelines. Recent reports have shown that statins treatment in NAFLD patients may result in the reduction of CV risk than prevent them from a cardiovascular event. However, the efficacy of statins on those patients was not ascertained by adequate evidence and remains controversial.
Objectives
To find and summarise as much as we could the presently available evidence of statins treatment on CV fatality and morbidity in patients with non-alcoholic fatty liver disease then draw final conclusion whether statins can reduce cardiovascular events in NAFLD patients or not, based on the reviewd data.
Methods
We conducted a computerized search for literature in the PubMed, EMBASE, Web of science, clinicaltrial.gov, sciencedirect.com and Cochrane library up to January 2019. There was no language restrictions or limitation for the publication date.
Inclusion criteria
Randomized clinical trials and observational studies which use statins as the intervention for patients with NAFLD compare with other lipid-lowering agents, usual care (no treatment) or placebo. Studies for inclusion must have evaluations on the cardiovascular outcome of participants. Participants were diagnosed with NAFLD or have elevated surrogate markers for NAFLD.
Data collection and analysis
Papers for inclusion were screened and selected by one authors. We then independently collected all available data and assessed for the risk of bias in each study. Meta-analyses, sensitivity analysis and publication bias were conduct wherever possible using Review Manager application version 5.2.
Results
After systematic search with the above method and the inclusion criteria, at first place, 877 records were found. In which 3 of them were the post-hoc analysis of randomized clinical trials and 1 cohort study that were considered eligible for inclusion. The total included population was 4329 participants.
We assessed all studies as high risk of bias. The three post-hoc analysis came from open-label RCTs and the comparability of the retrospective cohort study was unreliable.
Data about cardiovascular mortality were reported in the only one cohort study and the difference between 2 study arms was not statistically significant with the aHR = 1.2 (95% CI: 0.26-5.54) favour no medication group. There were consistent findings of cardiovascular morbidity which evaluated in 3 post-hoc analyses, that is, statin with a higher dose or more intensive treatment can reduce from 44% to 68% relative risk of cardiovascular events in the study population. Statistically significant improvement in the liver function tests, as well as lipid profile, was observed in the more intensive statin group compared with the placebo or moderate statin group. The present of NAFLD was significantly reduced by a higher dose of atorvastatin. NAFLD resolution rate was higher in group treated atorvastatin 34mg/day compare to group used atorvastatin 24mg/day (86% vs 74%; p = 0.0012).
Conclusions
From the findings in this systematic review, that contained four studies with moderate sample size and the high risk of bias, it appears that the use statins can benefit liver function tests and lipid levels as well as resolute NAFLD.
In terms of cardiovascular outcomes, we could not draw an ascertain conclusion about statins benefit for NAFLD patients. However, more intensive statin treatment can reduce CV morbidity in patients with a high risk of NAFLD (abnormal liver tests or elevated ALTs level). |
