Viral hepatitis increases the risk of cholangiocarcinoma: a systematic review and meta-analysis

Background: Whether viral hepatitis increases the risk of cholangiocarcinoma ( CCA) has been controversial. The reasons for the differences between previous research results may be related to the differences in sample size, region, living environment and course of disease. A meta- analysis is needed to clarify the correlation between them and select the key population for early screening of CCA. Meta-analysis was used to explore the relationship between viral hepatitis and the risk of CCA, so as to provide evidence for the prevention and treatment of CCA. Methods: We systematically searched EmBase, SinoMed, PubMed, Web of Science China National Knowledge Infrastructure, and Wanfang databases. The quality of the included literature was evaluated using the Newcastle Ottawa Scale. Before merging the effect quantities, the data was first subjected to heterogeneity testing. Heterogeneity testing was evaluated using I-2 (the proportion of heterogeneity variation to overall variation). Subgroup analysis was used to identify sources of heterogeneity in this study. The effect odds ratio (OR) of various studies was extracted or calculated for consolidation. Beta's rank correlation, Egger's Law of Return and funnel plot were used to test publication bias. Conduct subgroup analysis based on the regions included in the literature. Results: A total of 2,113 articles were retrieved, and a total of 38 articles were included in the metaanalysis. There are 29 case-control studies and 9 Cohort study, including 333,836 cases and 4,042,509 controls. The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis B virus (HBV) infection (OR =1.75, OR =1.49, and OR =2.46, respectively). The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis C virus (HCV) infection (OR =1.45, OR =2.00, and OR =2.81, respectively). The research points of HCV and CCA were asymmetric, indicating that there may be publication bias in the study of HCV and CCA. Conclusions: HBV and HCV infection could increase the risk of CCA. Therefore, in clinical practice, attention should be paid to CCA screening and early prevention of HBV and HCV infected patients.