Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH

Gastroenterology. 2006 Dec;131(6):1879-86. doi: 10.1053/j.gastro.2006.09.019. Epub 2006 Sep 20.


Background & aims: Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question.

Methods: The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping.

Results: HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma.

Conclusions: These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Data Interpretation, Statistical
  • Europe / epidemiology
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C / blood
  • Hepatitis C / complications*
  • Hepatitis C / epidemiology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / epidemiology*
  • Lymphoma, Large B-Cell, Diffuse / virology*
  • Male
  • Middle Aged
  • Prevalence
  • RNA, Viral / blood
  • Risk Factors


  • RNA, Viral