Pharmacotherapy-Induced Hepatitis B Reactivation Among Patients With Prior Functional Cure: A Systematic Review

To describe and quantify the incidence and morbidity of hepatitis B reactivation (HBVr) secondary to pharmaceutical agents (eg, rituximab, tumor necrosis factor inhibitors, direct-acting antivirals [DAAs] for hepatitis C) among patients with previously resolved hepatitis B infection.

The MEDLINE database was searched from inception through July 2018 using the terms hepatitis B + ( reactivation OR [drug or drug class linked to HBVr]).

Relevant English-language cohort studies or randomized trials quantifying the incidence of HBVr secondary to pharmacotherapy among patients negative for hepatitis B surface antigen and DNA and positive for hepatitis B core antibody were included.

Among 2045 articles, 102 met inclusion criteria. Receipt of rituximab was associated with the highest risk of HBVr (for oncological indication: 6.2% rate [225/3601 patients]) and subsequent hepatitis (up to 52.4% of all HBVr cases). Biologic agents for autoimmune disease were uncommonly associated with HBVr (2.4%, 56/2338), with only 4 cases of hepatitis, all attributable to rituximab. Reactivation caused by DAAs was rare (0.3%, 28/8398), with no cases of hepatitis. Relevance to Patient Care/Clinical Practice: This review compares and contrasts the incidence and clinical relevance of HBVr for various pharmacotherapies among patients with functionally cured hepatitis B, with discussion of appropriate risk mitigation strategies.

Among patients with prior functional cure of hepatitis B, prophylactic antiviral therapy is recommended with rituximab administration irrespective of indication because of a high risk for HBVr-associated morbidity. Enhanced monitoring alone is reasonable for patients receiving nonrituximab biologics or DAAs.