BackgroundNon-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA).MethodsA search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics.ResultsSeven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36–2.79, I
2=76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52–3.24, I
2=67%) and 1.55 (95%CI: 1.03–2.33, I
2=69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41–2.75, I
2=71%), 2.09 (95%CI, 1.49–2.91, I
2=42%) and 2.05 (95%CI, 1.59–2.64, I
2=0%) for all CCAs, iCCA, and eCCA, respectively.ConclusionsThis meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted.Trial registrationThe protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).Electronic supplementary materialThe online version of this article (10.1186/s12876-017-0696-4) contains supplementary material, which is available to authorized users.
