The present meta-analysis was conducted to evaluate the strength and the consistency of the association between hepatitis C virus (HCV) infection and non-Hodgkin lymphoma (NHL) and other lymphoid neoplasms. Only studies with >= 100 cases which were also adjusted for sex and age were included. Fifteen case-control studies and three prospective studies contributed to present analysis, nine of which had not been included in previous meta-analyses. We calculated the pooled relative risks (RR) with corresponding 95% confidence intervals (95% CI), as a weighted average of the estimated RRs by random-effect models. The pooled RR of all NHL among HCV-positive individuals was 2.5 (95% CI, 2.1-3.0), but substantial heterogeneity was found between studies and by study design. Pooled RRs were 2.5 (95% CI, 2.1-3.1) in case-control studies and 2.0 (95% CI, 1.8-2.2) in cohort ones. The strongest source of heterogeneity seemed to be the prevalence of HCV among NHL-free study subjects (RR for NHL among HCV-positive individuals 3.0 and 1.9, respectively, for >= 5% and < 5% HCV prevalence). RRs were consistently increased for all major B-NHL subtypes, T-NHL, and primary sites of NHL presentation. Thus, previous suggestions that the RRs for HCV differed by NHL subtype were not confirmed in our meta-analysis. Associations weaker than with NHL were found between HCV infection and Hodgkin's lymphoma (RR, 1.5; 95% CI, 1.0-2.1) and multiple myeloma (RR, 1.6; 95% CI, 0.7-3.6), but they were based on much fewer studies than NHL. The etiologic fraction of NHL attributable to HCV varies greatly by country, and may be upward of 10% in areas where HCV prevalence is high.
