Treatment of Chronic HCV Infection in Patients With Lymphoma Tied to Improved Overall Survival

A relationship between hepatitis C and cancer is reinforced by data from epidemiologic research.

Chronic hepatitis C virus infection (HCVI) is not only a disease of the liver, but also has effects on other parts of the body in many patients. These other effects, known as extrahepatic manifestations, may include lichen planus, porphyria cutanea tarda, and cryoglobulinemia with vasculitis.

Some patients may even develop polyclonal bands of proteins that appear in electrophoresis studies of patient blood samples. Such bands also commonly appear in blood cancers, such as multiple myeloma, lymphoma, and leukemia. These extrahepatic manifestations are believed to result from improperly folded proteins in HCV-infected cells.

The strong suggestion of a relationship between HCVI and cancers is further reinforced by data from epidemiologic research. For instance, patients with chronic HCVI are 2 to 4 times more likely to develop B-NHL than members of the general population.

Because there is a relationship between HCV and lymphoma-like features, physician-researchers Jean-Marie Michot, Danielle Canioni, Henda Driss, and colleagues practicing in several French hospitals and research institutions, investigated the effect of antiviral therapy in patients with HCV-associated B-cell non-Hodgkin lymphoma (B-NHL).

The study, known as the ANRS HC-13 Lympho-C study, included 116 patients with both B-NHL and chronic HCVI recruited over a 6-year period ending in 2012. Upon diagnosis, patients in the study had a median age of 61 years, and had an estimated median duration of chronic HCVI before development of B-NHL of 25 years. Patients had different cytohistological types of B-cell malignancies, including marginal zone lymphoma, diffuse large B-cell lymphoma, and miscellaneous cytopathologies. In the observational study, patients were treated with standard chemotherapies and monitored at 6-month intervals over 5 years.

Of patients receiving antiviral therapy for HCV, rates of 3-year overall survival were significantly better than in patients who did not receive treatment for chronic HCV infection. In all patients, more than three-fourths (78%) of antiviral therapy recipients survived at least 3 years, and nearly two-thirds (64%) were free of cancer progression over the same time period. Results in patients who received anti-HCV treatment were significantly better than results in untreated patients (P = .05), with even data suggesting an even greater benefit in patients with marginal zone lymphoma than in groups with diffuse large B-cell lymphoma (P = .04).

Antiviral treatments in this trial included pegylated interferon alpha and ribavirin for the majority of patients. A small minority of patients (n = 6) also received an oral protease inhibitor (ie, boceprevir or telaprevir). These treatments have since been supplanted by more modern direct-acting antivirals.

Most deaths in the study occurred due to opportunistic infections other than HCV. As a result, investigators noted the importance of preserving immunity in patients with HCV and B-NHL. Strategies for preserving immunity may include both through curative treatment of HCVI and use of less immunotoxic chemotherapy in patients with low-grade lymphoma.

In their conclusion, investigators stated, “Antiviral treatment in HCV-positive NHL could reinforce the results of a successful chemotherapy.” In addition, for some patients, “[antiviral] should be proposed when lymphoma remission is obtained, taking into account the risk/benefit ratio of antiviral treatment.”

Whether or not targeted antiviral therapy had a direct role in changing response rates to lymphoma remains undetermined. Although HCV is linked to development of B-NHL, and treatment of HCV is linked to improved survival and tends to improve progression-free survival as well, whether or not the antiviral therapy has a direct effect on lymphoma remains unknown.

As more and more patients receive anti-HCV therapy, future studies may determine whether or not broad use of anti-HCV therapies reduce lymphoma incidence rates across the general population. Whether or not B-NHL can be prevented through early treatment has yet to be determined. However, an overall survival benefit with curative HCV therapy suggests a therapeutic role of antivirals in targeting some of the underlying factors involved in carcinogenic processes.