Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies
Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies
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DOI：
10.1371/journal.pmed.1003100
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发表时间：
2020-04-01
期刊：
影响因子：
15.8
通讯作者：
Hanratty, Barbara
中科院分区：
文献类型：
--
作者：
Jarvis, Helen;Craig, Dawn;Hanratty, Barbara
背景非酒精性脂肪肝病（NAFLD）是全世界慢性肝病的主要原因。许多人存在与 NAFLD 相关的危险因素，但大多数人不会发展为晚期肝病：肝硬化、肝功能失代偿或肝细胞癌。识别出现这些并发症的高风险人群对于预防疾病进展非常重要。这篇综述综合了代谢危险因素的证据，及其预测有 NAFLD 风险或诊断出 NAFLD 的一般人群肝病结果的潜力。方法和结果我们对基于人群的队列研究进行了系统回顾和荟萃分析。数据库（包括 MEDLINE、EMBASE、Cochrane 图书馆和 ClinicalTrials.gov）的检索截止日期为 2020 年 1 月 9 日。纳入的研究报告了与无代谢风险因素的成人相比，有代谢风险因素的成年个体出现严重肝病结局（定义为肝硬化、肝硬化并发症或肝脏相关死亡）或晚期纤维化/非酒精性脂肪性肝炎 (NASH) 因素。根据临床指示的肝活检选择的队列被排除在外，以更好地反映一般人群的风险。使用 QUIPS 工具评估偏倚风险。汇集类似研究的结果，并使用随机效应荟萃分析获得风险比（HR）的总体估计。在 7,300 篇独特的引用中，22 项研究符合纳入标准并且质量足够，其中 18 项研究提供的数据适合合并在 2 项随机效应荟萃分析中。 2 型糖尿病 (T2DM) 与发生严重肝病事件的风险增加相关（调整后 HR 2.25，95% CI 1.83-2.76，p < 0.001，I-2 99%）。 T2DM 数据来自 12 项研究，对 2280 万人进行了中位数 10 年（IQR 6.4 至 16.9）的随访，经历了 72,792 起肝脏事件。将肥胖（BMI > 30 kg/m(2)）作为预后因素的荟萃分析纳入了 14 项研究，提供了 1,930 万名个体的数据，随访时间中位数为 13.8 年（IQR 9.0 至 19.8），经历了 49,541 起肝脏事件。肥胖与发生严重肝病结果的风险适度增加相关（调整后的 HR 1.20，95% CI 1.12-1.28，p < 0.001，I-2 87%）。还有证据表明，脂质异常（低高密度脂蛋白和高甘油三酯）和高血压均与严重肝病的发生独立相关。荟萃分析中观察到的显着研究异质性和较小的阴性研究可能发表不足被认为是局限性，以及竞争风险对结果的潜在影响。结论在这篇综述中，我们观察到 T2DM 与发生严重肝病的风险增加 2 倍以上相关。随着糖尿病和肥胖症的发病率持续上升，利用这些发现来改善肝病高危人群的病例发现，将有助于进行有效的管理，帮助解决肝病发病率和死亡率不断上升的问题。
BackgroundNon-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD.Methods and findingsWe conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I-2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta -analysis of obesity (BMI > 30 kg/m(2)) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I-2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome.ConclusionsIn this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease.