Hepatitis B and C virus infections and anti‐tumor necrosis factor‐α therapy: Guidelines for clinical approach

Abstract

Anti-tumor necrosis factor-α (TNF) therapy has recently been recognized to be associated with activation of hepatitis B virus (HBV) infection, with a potentially fatal outcome, mirroring experience in the setting of immune suppression and subsequent reconstitution in cancer chemotherapy and transplantation. Although there is no current evidence that anti-TNF therapy influences the natural history of hepatitis C virus (HCV) infection, the involvement of TNF in the pathogenesis of hepatic injury and extrapolation from other clinical situations heighten awareness of a potential conflict. Preventive strategies should be mandatory. These include screening of all patients for HBV and HCV infection prior to commencement of anti-TNF therapy, and active monitoring of aminotransferases and, for HBV, viral load during and for 3 months after therapy has terminated. Prophylactic or early intervention strategies with nucleoside analogs are recommended for patients with evidence of HBV infection.

Safety of tumor necrosis factor α blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti–hepatitis B core antigen positive) with rheumatic diseases

“…Of 732 patients, 72 were identified as anti-HBc carriers, but 5 of them were HBsAg positive and therefore were not enrolled in the study; the latter were treated with lamivudine prophylaxis before the onset of anti-TNF␣ therapy, and are still under treatment in accordance with the current guidelines (4,32). Sixty-seven patients were included in the study.…”

“…On the other hand, many cases have been described in which TNF blockade, either in association with lamivudine prophylactic therapy or not, did not lead to HBV reactivation (6,(25)(26)(27)(28)(29)(30), and recently a retrospective study showed no reactivation during anti-TNF␣ therapy (31). The use of lamivudine to prevent HBV reactivation is recommended in HBsAg-positive patients undergoing immunosuppressive therapies, including anti-TNF␣ drugs (4,32), but its use can lead to viral resistance (33). There are no prospective studies regarding HBV reactivation and TNF␣ blocker therapy, and in particular few data are available about HBsAg-negative, antiHBc-positive patients.…”

Reactivation of chronic hepatitis B virus infection following rituximab administration for rheumatoid arthritis

“…On the other hand, a diagnosed chronic HBV infection may cause delay to or undertreatment of patients with rheumatic diseases. Reactivation of chronic HBV infection has been reported with anti-TNF agents (6,7). However, under prophylactic antiviral treatment these agents seem, at least in a restricted number of patients and under short-term follow up, to be relatively safe (8,9).…”

Viral infection and reactivation in autoimmune disease

“…In a recent review of the literature describing patients with HBV infection who had been treated with TNF inhibitors, the authors reported that ϳ50% of such patients experienced hepatitis flares (33), and acute flare of HBV infection has been reported to occur 2-3 months after infliximab withdrawal (34). Serious sequelae, including deaths, have occurred in patients with previously asymptomatic HBV infection who had normal results of liver tests and no detectable viral replication before treatment with immunosuppressive drugs (31,32,34,35).…”