Association Between Non-alcoholic Fatty Liver Disease and Risk of Stroke: A Systematic Review and Meta-Analysis

Abstract

Background/objectives: Recent observational studies have explored the association between non-alcoholic fatty liver disease (NAFLD) and stroke with controversial results. We therefore performed a meta-analysis to investigate this possible association.

Methods: PubMed, EMBASE and Web of Science database were searched from inception until December 2019, and updated on May 2021. Random-effects meta-analyses were performed by generic inverse variance method. Subgroup and sensitivity analyses were also conducted. The PROSPERO registered number of this study is CRD42020167330.

Results: Twenty observational (15 cohort, 4 cross-sectional, and 1 case-control) studies with 17,060,388 participants were included in the meta-analysis. Meta-analysis of data from 18 studies with 17,031,672 participants has shown that NAFLD was associated with mildly increased risk of stroke (OR = 1.18, 95% CI: 1.08-1.30, P = 0.0005). Similar results were observed in most of the subgroup analyses we performed. Sensitivity analyses did not alter these findings. Meta-analysis of data from 3 studies with 29,614 participants has shown that insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke.

Conclusions: We found that NAFLD was associated with increased risk of stroke. However, there was insufficient evidence to support the proposed association between NAFLD-fibrosis and an increased risk of stroke. To better understand any association, future well-designed prospective studies that take fully account of specific population, type of stroke, and confounding factors are warranted.

Systematic review registration: Unique Identifier: CRD42020167330.

Keywords: meta-analysis; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; stroke; systematic review.