Hepatitis E virus infection and risk of hepatocellular carcinoma: A systematic review and meta-analysis

The potential role of hepatitis E virus (HEV) infection in developing hepatocellular carcinoma (HCC) is controversial and poorly investigated. We conducted a meta-analysis of observational studies to evaluate whether HEV infection increases the risk of HCC.

We searched international databases (PubMed/Medline, Web of Science Collection, Embase, and Scopus) for peer-reviewed research articles published from inception to May 1, 2023. The pooled estimates of the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated using random-effects models. Between-study heterogeneity was measured using I² and Q-statistic. Sensitivity and cumulative analyses were performed to examine the stability of our results.

We identified seven eligible studies involving 1873 HCC cases and 8679 control subjects; the latter included 7382 healthy controls and 1297 patients with chronic liver diseases (CLD). Overall, we observed statistically significant associations between HEV infection and risk of HCC (OR 1.94; 95%CI 1.26-3.0). According to the types of the controls, the association was significant when healthy individuals were the controls (OR 2.28, 95%CI 1.43-3.64), whereas the association was not significant when the patients had CLD (OR 1.66, 95%CI 0.76-3.61). The Egger's test and funnel plot indicated that there is no publication bias (p = 0.1) in the studies included in the meta-analysis. Sensitivity and cumulative analyses also indicated stability of our results.

Our findings indicate that individuals with HEV infection had an increased risk of HCC; however, further well-designed clinical and experimental studies are needed to confirm these observations. Furthermore, whether various genotypes of HEV differ in promoting HCC also needs to be investigated.