Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta‐analysis

Abstract

To assess the effects of prophylactic lamivudine on reactivation and mortality following immunosuppressive therapy in hepatitis B surface antigen (HBsAg)-positive patients, we performed a meta-analysis. Systematic review and meta-analysis of randomized and nonrandomized prospective controlled trials and retrospective comparative case series were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. The primary outcomes were virological reactivation, clinical reactivation and mortality. Secondary outcomes included hepatitis B virus (HBV)-related mortality, liver histology, discontinuation or disruption of immunosuppressive therapy, lamivudine-resistant HBV strains and adverse events. A total of 21 studies were included, two of which were randomized controlled trials. Clinical and virological reactivation were significantly reduced in the lamivudine group [odds ratio (OR) 0.09; 95% confidence interval (CI) 0.05-0.15 and OR 0.04; 95% CI 0.01-0.14 respectively]. All-cause mortality was significantly reduced in the lamivudine group (OR 0.36; 95% CI 0.23-0.56) which translates to only 11 patients who need to be treated to prevent one death. Lamivudine significantly reduced HBV-related mortality, and discontinuations or disruptions of the immunosuppressive treatment. No adverse effects of lamivudine were recorded, and resistance to lamivudine occurred in low rates. We demonstrated a clear benefit of lamivudine in terms of clinical and virological HBV reactivation, overall mortality, HBV-related mortality and interruptions or discontinuations in the immunosuppressive treatment. Lamivudine should be administered prophylactically to HBsAg-positive patients who are about to receive immunosuppressive therapy.

Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease

“…[64][65][66] One meta-analysis of lamivudine for prophylaxis of HBV reactivation in immunosuppressed patients included 21 studies and showed that this drug reduced mortality. 67 The American Association for the Study of Liver Disease (AASLD), 68 the European Association for the Study of the Liver (EASL) 68 and the European Crohn and Colitis Organization (ECCO) 16 recommend early introduction of nucleoside ⁄ nucleotide analogues for all HBsAgpositive patients requiring immunosuppressive therapy. Anti-viral therapy should be administered to those patients who exhibit positive HBsAg titres with or without active viral replication.…”

Screening for Hepatitis B Surface Antigen before Chemotherapy: Current Practice and Opportunities for Improvement

“…The potential clinical consequences of hbv reactivation include liver damage from reactivation hepatitis, interruption of cancer treatment, and a mortality rate of up to 5% 7 . Prophylaxis with anti-hbv nucleoside/nucleotide analogs such as lamivudine reduces the incidence and severity of reactivation hepatitis in hbv carriers receiving chemotherapy [8][9][10][11][12] .…”

Follow-up of the Chronic HBV Infected Patients Planned Chemotherapy Due to Solid Organ Malignancy

“…They concluded that clinical (OR= 0.09; 95% CI 0.05-0.15) and virological HBV reactivation rates (OR= 0.04; 95% CI 0.01-0.14) as well as HBV-related mortality were significantly reduced (OR= 0.20; 95% CI 0.09-0.45) in the lamivudine group. 32 In our study, group III (chronic HBV infection), two patients with HBV reactivation had neither serious reactivation nor hepatitis clinic which may be associated with their below the detectable level of HBV-DNA levels at the beginning of chemotherapy. When evaluating the reactivation phases associated with HBV, lamivudine prophylaxis may have a possible mechanism of inhibiting new hepatocytes from infection by suppressing the increase of viral replication occurring in the first phase of the reactivation and preventing hepatocyte damage associated with the reconstitution of the second phase immune system.…”