Nonalcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta‐analysis

BACKGROUND: Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra-hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta-analysis of relevant studies to examine the association between NAFLD and the risk of GERD. METHODS: We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross-sectional, case-control and cohort studies investigating the association between NAFLD and GERD. RESULTS: Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta-analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12-1.44, I2  = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03-1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62-2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association. CONCLUSION: NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.