Abstract

Background: The association between ABO and Rhesus (Rh) blood groups and susceptibility to hepatitis C virus (HCV) infection remains uncertain. This systematic review and meta-analysis aimed to clarify these associations. Methods: PubMed, Scopus, Embase, and MEDLINE were searched from inception to 23 January 2025. Studies reporting HCV infection by ABO and/or Rh blood group were eligible. Risk of bias was assessed using the NIH tools. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with the I² statistic. Subgroup, sensitivity, and publication bias analyses were also performed. The protocol was registered in PROSPERO (CRD420250635714). Results: Thirty-eight studies comprising 3,404,016 participants were included. No significant associations were observed for blood groups A (OR = 1.03, 95% CI: 0.97–1.10), AB (OR = 0.99, 95% CI: 0.85–1.17), O (OR = 0.94, 95% CI: 0.85–1.06), or Rh factor (OR = 0.99, 95% CI: 0.87–1.12). In contrast, blood group B was associated with an 11% higher odds of HCV infection (OR = 1.11, 95% CI: 1.02–1.22, p = 0.02). This association remained robust in sensitivity analyses. Heterogeneity was generally low to moderate, and Egger’s test indicated no evidence of publication bias. Conclusions: ABO and Rh blood groups were not strongly associated with HCV infection, except for a consistent positive association with blood group B. Interpretation remains limited by study design and methodological variability. Therefore, large, prospective, multi-regional studies with standardized protocols are needed to validate these findings and explore potential biological mechanisms.