Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11054
Revised: February 25, 2014
Accepted: May 29, 2014
Published online: August 28, 2014
A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.
Core tip: Patients with hepatitis C virus-positive diffuse large B-cell lymphoma should be managed in a multidisciplinary setting. Initial evaluation of liver status and comorbidities is essential to establish if the patient is candidate to curative approaches. Unless contraindicated by adverse clinical conditions, patients should be treated with standard immuno-chemotherapy. Concomitant hepatitis B virus infection and liver failure or cirrhosis confer a significantly higher risk of viral reactivation or therapy related complications. These patients should be managed cautiously and treated with less intense approaches at least for the initial cycles. Antiviral treatment should be considered after the end of immuno-chemotherapy, when lymphoma remission has been achieved.