Hepatitis C virus infection is significantly associated with malignant lymphoma in Taiwan, particularly with nodal and splenic marginal zone lymphomas

Aims Hepatitis C virus (HCV) is a hepatotropic and lymphotropic RNA virus causally linked to lymphoma with a strong geographic variation. The aim of this study was to investigate the association of HCV and lymphoma in Taiwan, in which HCV is endemic. Methods Patients diagnosed with lymphoma from January 2004 to December 2008 were investigated for serum anti-HCV, and the infection rate was compared with that in healthy controls. Various lymphoma types were investigated for HCV infection. Immunohistochemistry was performed for HCV nonstructural (NS) 3 protein, and genotyping was performed by reverse transcriptase PCR. Results Thirty-eight (11.0%) of 346 patients with lymphoma were positive for anti-HCV, as compared with 15 (1.8%) of 824 healthy controls (p<0.001, chi(2) test) with an age-adjusted and sex-adjusted OR of 4.57 (95% CI 2.41 to 8.68). Only nodal (five of eight cases) and splenic (two of two cases) marginal zone lymphomas (MZLs) as a group were significantly associated with HCV, as compared with mucosa-associated lymphoid tissue (MALT) lymphomas (1 of 15; p 0.002, Fisher's exact test). All 26 anti-HCV-positive cases stained for HCV-NS3 were negative. The most common genotypes were 1b (22%) and 2a (56%), with no statistical difference from 203 patients with HCV-related chronic liver disease. Conclusions The incidence of HCV infection among lymphoma patients in Taiwan was significantly higher than that for healthy controls. Furthermore, non-MALT (nodal and splenic) MZL was the only group significantly associated with HCV. A larger national study is warranted to re-confirm our findings and to elucidate if any particular HCV genotypes were related to the pathogenesis of lymphoma.