In patients with previously cured hepatitis B infection, antiviral therapy should be used prophylactically when rituximab is administered, irrespective of indication, due to a high risk of hepatitis B reactivation (HBVr)-associated morbidity, according to results of a recently published systematic review.

The study aimed to determine the incidence and morbidity of HBVr associated with pharmaceutical agents such as rituximab, tumor necrosis factor inhibitors, and direct-acting antivirals (DAAs). The study authors searched MEDLINE from inception through July 2018 to obtain relevant cohort studies and randomized trials assessing HBVr incidence secondary to pharmaceutical agents. Patients that were included in the study were “negative for hepatitis B surface antigen and DNA and positive for hepatitis B core antibody.”

Of the 2045 articles obtained, 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),” the study authors reported. They added, “Biologic agents for autoimmune disease were uncommonly associated with HBVr (2.4%, 56/2338), with only 4 cases of hepatitis, all attributable to rituximab.” Results of the study also found that DAAs rarely caused reactivation (0.3%; 28/8398) and zero cases of hepatitis were reported.

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Due to the high risk of HBVr, it is important to consider utilizing prophylactic antiviral therapy with rituximab administration in patients with previously cured hepatitis B infection. Since non-rituximab biologics and DAAs were associated with a lower risk of HBVr, only enhanced monitoring is recommended.


Bath RM, Doering BE, Nailor MD. Pharmacotherapy-induced hepatitis B reactivation among patients with prior functional cure: A systemic review. Annals of Pharmacotherapy. 2018.

This article originally appeared on MPR