Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg?

Abstract

Reactivation of hepatitis B in the context of immunosuppressive therapy may be severe and potentially fatal. The US Food and Drug Administration has recently drawn attention to the potentially fatal risk of hepatitis B reactivation in patients receiving the anti-CD20 agents ofatumumab or rituximab. This action focuses attention on the broader issue of hepatitis B virus reactivation, which may occur with a wide variety of immunosuppressive therapies in benign or malignant disease. This article summarizes the data behind this issue. These data support the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral infection by testing for hepatitis B surface antigen and the antibody to hepatitis B core antigen in serum. Those who are found to be hepatitis B surface antigen-positive should start appropriate antiviral therapy to prevent reactivation. Additionally, even those who have recovered from hepatitis B will benefit from antiviral therapy in certain circumstances because of the risks associated with a form of hepatitis B virus reactivation referred to as "reverse seroconversion." There remain many uncertain areas that warrant further study, and further advances will benefit from close interactions between various medical specialties, regulatory agencies, and researchers.

Conclusions: There is good evidence to support routine screening of all patients for hepatitis B prior to undergoing chemotherapy or immunosuppressive treatment; use of prompt antiviral treatment appears to diminish the risk of severe or fatal reactivation of hepatitis B.

Conflict of interest statement

Potential conflicts of interest: Dr. Di Bisceglie consults for and received grants from Gilead and Bristol-Myers Squibb; Dr. Martin consults for Gilead and Bristol-Myers Squibb; Dr. Lok consults and received grants from Gilead, advises GlaxoSmithKline, and received grants from Bristol-Myers Squibb; Dr. Perrillo advises Novartis and is on the speakers’ bureau for Gilead and Bristol-Myers Squibb; Dr. Terrault advises Bristol-Myers Squibb and received grants from Gilead.

© 2014 by the American Association for the Study of Liver Diseases.

Figures

Fig. 1

Pattern of typical serological and biochemical changes associated with HBV reactivation (based on examples in Hoofnagle). Abbreviations: ALT, alanine aminotransferase.

Fig. 2

Recommended algorithm for HBV testing and treatment in patients undergoing immunosuppressive therapy.