| Summary: | Background and aim: With conflicting data from previous observational studies on the relationship between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and pancreatic cancer (PC), we decided to conduct a systematic review and meta-analysis in order to evaluate any potential association. Design: This is a systematic review and meta-analysis. Methods: We conducted a search of three databases (PubMed, Embase, and Web of Science) from the time of their creation up to June 2023. The summary results, including hazard ratio (HR) with 95% confidence interval (CI), were pooled using a generic inverse variance method and a random-effects model. Furthermore, subgroup and sensitivity analyses were conducted. Results: In this meta-analysis, 22 cohort studies with a total of 10,572,865 participants were analyzed. Meta-analysis from 15 cohort studies revealed that HBV infection was correlated with an increased risk of PC (HR = 1.53, 95% CI: 1.40–1.68, p < 0.00001) with no heterogeneity ( I 2 = 0%, p = 0.49). Meta-analysis from 14 cohort studies showed that HCV infection was associated with an increased risk of PC (HR = 1.82, 95% CI: 1.51–2.21, p < 0.00001). Most of our subgroup analyses yielded similar results. Meta-analysis from four cohort studies indicated that co-infection with HBV and HCV was linked to an increased risk of PC (HR = 2.32, 95% CI: 1.40–3.85, p = 0.001) with no heterogeneity observed ( I 2 = 0%, p = 0.60). The results of sensitivity analyses were robust. Conclusion: Our meta-analysis showed that HBV/HCV infection or co-infection with HBV and HCV was associated with an increased risk of PC. Future prospective cohort studies need to take into account various ethnicities and any confounding factors, as well as investigate the potential mechanisms of PC development in those with HBV/HCV. Trial registration: Open Science Framework registries (No: osf.io/n64ua).
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