Most Patients With HCV-associated Lymphoma Present With Mild Liver Disease

A Call to Revise Antiviral Treatment Prioritization

Harrys A. Torres; Parag Mahale


Liver International. 2015;35(6):1661-1664. 

In This Article

Abstract and Introduction


Background & Aims Hepatitis C virus (HCV) is associated with development of B-cell non-Hodgkin lymphoma (HCV-NHL). Antiviral therapy (AVT) is prioritized in HCV-infected patients with significant fibrosis/cirrhosis. It is unknown whether current recommendations based on liver parameters cover the risk of HCV-NHL development. We aimed to evaluate the liver disease stages of patients with HCV-NHL.

Methods Hepatitis C virus-NHL patients seen at MD Anderson Cancer Center between 2008 and 2014 were evaluated for underlying liver disease within a year of HCV-NHL diagnosis by non-invasive fibrosis markers, radiology or liver biopsy. Included patients were observed retrospectively (2008–2012) or prospectively (2012–2014).

Results Eightynine patients with HCV-NHL were evaluated. Most patients had genotype 1 (62%) infection, had diffuse large B cell lymphomas (62%), and detectable HCV RNA (90%) at NHL diagnosis. Notably, advanced liver disease (Metavir stage ≥ 3) was present in only 18% of the patients at the time of HCV-NHL diagnosis. All 53 patients with chronic HCV infection documented before lymphoma diagnosis were seen by HCV-treating physicians. Providers did not recommend AVT in almost one half of cases (44%), mostly because of the lack of advanced liver disease at HCV diagnosis (38%).

Conclusions Most patients with HCV-NHL have mild liver disease at cancer diagnosis. Our findings suggest the need for early initiation of AVT in infected patients to eradicate HCV infection and its extra-hepatic manifestations. Treatment prioritization and cost must be weighed against the potential benefits of preventing NHL.


Hepatitis C virus (HCV) infection is an established risk factor for cirrhosis and hepatocellular carcinoma.[1] Anti-HCV seropositivity also increases mortality from several extra-hepatic diseases, including non-liver cancers.[2] HCV is a lymphotropic virus and has been associated with several lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (NHL).[3–6] Prevalence of HCV infection in patients with B-cell NHL has been reported to be as high as 15%,[7] with multiple reports of lymphoma regression after antiviral therapy and attainment of sustained virological response (SVR).[3,5,8] A retrospective study reported lower cumulative incidence rates of lymphoma in HCV-infected patients treated with interferon (IFN) therapy as compared with those who were untreated, suggesting possible prevention of B-cell NHL using HCV therapy.[9]

Current HCV treatment recommendations are mainly based on the severity of underlying liver disease. Recent HCV treatment guidelines suggest that 'highest priority' should be given to patients with advanced liver disease (Metavir score F3–F4), liver transplant recipients and patients with severe extrahepatic manifestations; but concerns regarding B-cell NHL were not addressed.[10]

None of the epidemiological studies of the association between HCV infection and NHL have evaluated patients' liver fibrosis stage at cancer diagnosis. It is essential to determine whether current recommendations based on liver-related parameters cover the risk of development extra-hepatic manifestations of HCV infection such as B-cell NHLs. In this study, we aimed to ascertain the liver disease status of such patients and hypothesize that most patients with HCV-associated NHL present with mild liver disease at cancer diagnosis.