Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy.

Abstract

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.

• Authors: Nobuhiko Yamauchi, Dai Maruyama, Ilseung Choi, Yoshiko Atsuta, Rika Sakai, Kazuho Miyashita, Yukiyoshi Moriuchi, Hideki Tsujimura, Nobuko Kubota, Go Yamamoto, Tadahiko Igarashi, Koji Izutsu, Shinichiro Yoshida, Kensuke Kojima, Toshiki Uchida, Yoshiko Inoue, Norifumi Tsukamoto, Eiichi Ohtsuka, Sachiko Suzuki, Yoko Inaguma, Satoshi Ichikawa, Hiroshi Gomyo, Yoko Ushijima, Kisato Nosaka, Mio Kurata, Yasuhito Tanaka, Ryuzo Ueda, Masashi Mizokami, Shigeru Kusumoto
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 5 Pg. 1943-1954 (May 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 33576088 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antineoplastic Agents, Immunological
• Antiviral Agents
• DNA, Viral
• Hepatitis B Surface Antigens
• R-CHOP protocol
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• pirarubicin
• Alanine Transaminase
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Alanine Transaminase (blood)
• Antineoplastic Agents, Immunological (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Antiviral Agents (therapeutic use)
• Case-Control Studies
• Cyclophosphamide (administration & dosage)
• DNA, Viral (blood)
• Doxorubicin (administration & dosage, analogs & derivatives)
• Female
• Hepatitis B (blood, drug therapy, epidemiology)
• Hepatitis B Surface Antigens (blood)
• Hepatitis B virus (genetics)
• Humans
• Incidence
• Induction Chemotherapy (methods)
• Japan (epidemiology)
• Liver Function Tests
• Lymphoma, Large B-Cell, Diffuse (blood, drug therapy, immunology, virology)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Retrospective Studies
• Rituximab (administration & dosage, therapeutic use)
• Survival Analysis
• Vincristine (administration & dosage)
• Virus Activation