Association between hepatitis C virus and non-hodgkin’s lymphoma, and effects of viral infection on histologic subtype and clinical course

PURPOSE: Because an etiologic role for hepatitis C virus in non-Hodgkin’s B-cell lymphoma has been suggested by several reports, we assessed the prevalence of hepatitis C virus infection in patients with non-Hodgkin’s B lymphoma and in controls, and evaluated the influence of viral infection on histologic and clinical features of the lymphoma patients. PATIENTS AND METHODS: We prospectively investigated 175 consecutive patients with non-Hodgkin’s lymphoma and 350 controls for serologic and molecular markers of hepatitis C virus infection. Controls were selected from inpatients (n = 175) and outpatients (n = 175) cared for at our hospital. Patients with lymphoma who had hepatitis C virus infection were tested for mixed cryoglobulinemia. Aminotransferase levels were measured in all lymphoma patients at baseline and during and after chemotherapy. RESULTS: Hepatitis C virus prevalence in patients with non-Hodgkin’s lymphoma was significantly greater than in control subjects (37% vs 9%, P = 0.0001). Among patients with lymphoma, viral infection was associated with older mean (±standard deviation) age (67 ± 14 vs 61 ± 8 years, P = 0.001), and women (41 of 87, 47%) were more likely than men (24 of 88, 27%) to have evidence of hepatitis C infection (P = 0.006). Thirteen of the 20 cases of immunocytoma were associated with hepatitis C virus infection, which was also more common in patients with orbital and conjunctival localization of lymphoma. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach were less likely to have evidence of hepatitis C infection. Mixed cryoglobulinemia was much more common in patients with hepatitis C virus infection (14 of 65 vs 1 of 110, P = 0.0001); it was not associated with the histologic type of lymphoma. Patients with and without hepatitis C virus infection underwent similar chemotherapy regimens and had no differences in response to chemotherapy or in overall and disease-free survival. Hepatic toxicity from chemotherapy was seen only in patients with hepatitis C virus infection, although all but one of these patients were able to complete their planned treatment. CONCLUSION: These findings suggest that the hepatitis C virus may have a role as an etiologic agent in non-Hodgkin’s B-cell lymphoma. Some clinical and pathologic features of the disease are associated with hepatitis C virus infection, but the virus does not seem to affect prognosis.