title: Comprehensive outcomes of on- and off-antiviral prophylaxis in hepatitis B patients undergoing cancer chemotherapy: A competing risks analysis.
abstract: Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seon-Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jonggi
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Danbi
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kang Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yung Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Vievisnamuh Hospital, Seoul, Republic of Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Suh
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: antiviral prophylaxis; cancer; chemotherapy; hepatitis B virus; reactivation; relapse