Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis

Background: Non-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). Methods: A 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. Results: Seven 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. Conclusions: This 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.