A Comparison of Entecavir and Lamivudine for the Prophylaxis of Hepatitis B Virus Reactivation in Solid Tumor Patients Undergoing Systemic Cytotoxic Chemotherapy

Background Nucleos(t)ide analogues reduce the incidence of hepatitis B virus (HBV) reactivation in cancer patients undergoing systemic cytotoxic chemotherapy but the experience of solid tumors remains limited. Aims. The aim of this study was to compare the efficacy of entecavir and lamivudine in the prophylaxis of HBV reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy. Methods HBsAg seropositive patients undergoing systemic cytotoxic chemotherapy for solid tumors with prophylactic entecavir and lamivudine between January 2006 and June 2013 were retrospectively investigated. The incidence of HBV reactivation and outcome of the patients were analyzed. The risk factors of HBV reactivation were examined. Results A total of 213 patients (entecavir group, 70 patients; lamivudine group, 143 patients) were evaluated. Less incidence of HBV reactivation was noticed in entecavir group than in lamivudine group (0% vs. 7.0%, P = 0.02). No HBV reactivation was noticed in the patients with a baseline HBV DNA level < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were significantly associated with HBV reactivation. Subgroup analysis of the patients with a baseline HBV DNA level ≥ 2000 IU/mL found that lamivudine was significantly associated with HBV reactivation. Most of the reactivation events were properly managed by using tenofovir disoproxil fumarate. The incidence of hepatitis during chemotherapy and disruption of chemotherapy was similar between patients using entecavir and lamivudine with a baseline HBV DNA level ≥ or < 2000 IU/mL. Conclusions A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were the risk factors of HBV reactivation during systemic cytotoxic chemotherapy in solid tumor patients. Entecavir was superior to lamivudine in terms of less incidence of reactivation in the patients with a baseline HBV DNA level ≥ 2000 IU/mL. Both agents were equally efficacious in the patients with HBV DNA levels < 2000 IU/mL.

[1]  Y. Falck‐Ytter,et al.  American Gastroenterological Association Institute Technical Review on Prevention and Treatment of Hepatitis B Reactivation During Immunosuppressive Drug Therapy , 2014 .

[2]  Tongyu Lin,et al.  Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. , 2014, JAMA.

[3]  Pei-Jer Chen,et al.  Chemotherapy‐induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: A prospective study , 2014, Hepatology.

[4]  C. Chu,et al.  Off‐therapy durability of response to entecavir therapy in hepatitis B e antigen‐negative chronic hepatitis B patients , 2013, Hepatology.

[5]  Chiun Hsu,et al.  Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: analysis from the Asia Lymphoma Study Group. , 2013, European journal of cancer.

[6]  V. Pattullo,et al.  Entecavir versus lamivudine for hepatitis B prophylaxis in patients with haematological disease , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[7]  Shou-Dong Lee,et al.  Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  W. Ling,et al.  Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours , 2013, British Journal of Cancer.

[9]  W. Yeo,et al.  Hepatitis B virus reactivation associated with anti‐neoplastic therapy , 2013, Journal of gastroenterology and hepatology.

[10]  Y. Kim,et al.  Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy , 2012, Antimicrobial Agents and Chemotherapy.

[11]  Jia-Horng Kao,et al.  Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update , 2012, Hepatology International.

[12]  EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. , 2012, Journal of hepatology.

[13]  Ding‐Shinn Chen,et al.  Serum hepatitis B virus-DNA levels correlate with long-term adverse outcomes in spontaneous hepatitis B e antigen seroconverters. , 2012, The Journal of infectious diseases.

[14]  Y. Xie,et al.  Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy , 2011, Journal of viral hepatitis.

[15]  Y. Cho,et al.  Rescue therapy for lamivudine‐resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add‐on lamivudine combination therapy , 2010, Journal of gastroenterology and hepatology.

[16]  T. Berg,et al.  Long‐term efficacy of tenofovir monotherapy for hepatitis B virus‐monoinfected patients after failure of nucleoside/nucleotide analogues , 2010, Hepatology.

[17]  D. Harnois Long-Term Efficacy of Tenofovir Monotherapy for Hepatitis B Virus-Monoinfected Patients After Failure of Nucleoside/Nucleotide Analogues , 2010 .

[18]  J. Hoofnagle,et al.  Systematic Review: The Effect of Preventive Lamivudine on Hepatitis B Reactivation during Chemotherapy , 2008, Annals of Internal Medicine.

[19]  G. Lau Hepatitis B reactivation after chemotherapy: two decades of clinical research , 2008, Hepatology international.

[20]  T. Mok,et al.  Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy , 2007, Hepatology.

[21]  A. Cross,et al.  A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. , 2006, The New England journal of medicine.

[22]  Ching-Lung Lai,et al.  Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. , 2006, The New England journal of medicine.

[23]  W. Yeo,et al.  Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy , 2006, Hepatology.

[24]  N. Leung,et al.  Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy , 2005, Gut.

[25]  T. Mok,et al.  Prevention of Hepatitis B Virus Reactivation in Patients With Nasopharyngeal Carcinoma With Lamivudine , 2005, American journal of clinical oncology.

[26]  T. Mok,et al.  Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  W. Lau,et al.  Outcome of lamivudine resistant hepatitis B virus mutant post‐liver transplantation on lamivudine monoprophylaxis , 2004, Clinical transplantation.

[28]  T. Mok,et al.  Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Ching-Lung Lai,et al.  Long-term safety of lamivudine treatment in patients with chronic hepatitis B. , 2003, Gastroenterology.

[30]  D. Fong,et al.  Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. , 2003, Gastroenterology.

[31]  W. Yeo,et al.  Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: A prospective study , 2003, Journal of medical virology.

[32]  W. Yeo,et al.  Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: A prospective study of 626 patients with identification of risk factors , 2000, Journal of medical virology.

[33]  W. Yeo,et al.  Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: Precore/core mutations may play an important role , 2000, Journal of medical virology.

[34]  D. Pillay,et al.  Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient , 2000, Gut.

[35]  Ding‐Shinn Chen,et al.  Hepatitis B Virus Infection , 2007 .

[36]  A. Lok,et al.  Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. , 1991 .

[37]  J. Hoofnagle,et al.  Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. , 1982, Annals of internal medicine.

[38]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .