Antiviral therapies for managing viral hepatitis in lymphoma patients

ABSTRACT

Introduction: In patients with lymphoma the detection of positive hepatitis B or C viruses (HBV and HCV) serology involves crucial therapeutic consequences. In HBV-infected patients the serological profile of active (HBsAg-positive) or resolved (HBsAg-negative/anti-HBcAb-positive) infection is associated to differential risk of viral reactivation during rituximab-based therapy and require appropriate strategies of monitoring and of antiviral prophylaxis. In HCV-associated NHL patients consolidated data demonstrated that interferon (IFN)-based antiviral therapy (AT) is able to induce lymphoma regression strictly related to viral eradication, while preliminary data of the new direct-acting antivirals (DAAs) are very promising.

Areas covered: This review summarizes current evidences about HBV reactivation risk in patients undergoing rituximab-based treatments and appropriate options of antiviral prophylaxis with lamivudine, entecavir or tenofovir, as well as pre-emptive strategy in HBsAg-negative/HBcAb-positive patients. Moreover previous experiences with IFN-based AT as well as recent studies with DAAs in HCV-associated indolent lymphomas or diffuse large B-cell lymphoma (DLBCL) are reviewed.

Expert opinion: Entecavir or tenofovir prophylaxis is recommended for HBsAg-positive patients, while universal prophilaxis with lamivudine may be preferred in HBsAg-negative/anti-HBc-positive patients. In asymptomatic patients with HCV-associated indolent lymphoma DAA-based AT should be used as first-line option, while in DLBCL its deliver after immunochemotherapy-induced complete remission is suggested.

KEYWORDS:

• Hepatitis B virus
• hepatitis C virus
• non-Hodgkin lymphoma
• antiviral therapy
• lamivudine
• entecavir
• tenofovir
• interferon
• direct-acting antivirals
• sofosbuvir

Article highlights

• In patients with newly diagnosed lymphoma the screening for HBV and HCV is of fundamental importance, as HBV- or HCV-positivity implicates critical consequences on the treatment choice and imply potential need of specific antiviral therapies.

• The risk HBV reactivation during or after rituximab-based treatment in patients with NHL is higher in HBsAg-positive patients but it may be estimated greater than 10% also in HBsAg-negative/anti-HBc-positive patients and deserves appropriate monitoring and/or antiviral prophylaxis strategies to prevent potential life-threatening hepatitis.

• A prospective randomized trial demonstrated superiority of ETV- over LMV-prophylaxis in reducing the risk of HBV reactivation (6.6% vs. 30%) and HBV-related hepatitis (0% vs. 13.3%) in HBsAg-positive patients with NHL undergoing R-CHOP.

• In HBsAg-negative/anti-HBc-positive NHL patients undergoing rituximab-chemotherapy two strategies may be adopted: the ‘pre-emptive’ anti-HBV therapy or the ‘universal prophylaxis’ with LMV or ETV.

• In patients with HCV-associated indolent NHL without need of immediate conventional treatment first-line IFN-based AT induced significant lymphoma response, which was strictly related to the achievement of viral eradication.

• Two studies demonstrated that IFN-based AT delivered ‘at any time’ is associated with an independent improvement of OS in patients with HCV-associated indolent NHL.

• The first large study evaluating IFN-free DAA-based AT in patients with HCV-positive indolent NHL demonstrated a 67% ORR (CR rate 26%). MZLs displayed the higher ORR (73%), while no patient with CLL/SLL responded.

• In patients with HCV-positive DLBCL the use of DAAs-based AT after achievement of R-CHOP-induced CR is a highly attractive strategy with the aim to improve the prognosis. Concurrent delivery of DAAs and R-CHOP may be of interest in cases with severe hepatic toxicity and may be tested in prospective clinical trials.

This box summarizes key points contained in the article.

Declaration of interest

L Arcaini received research support from Gilead Sciences Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

Funding

This paper is not funded.