Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4284-4292
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4284
Prophylactic antiviral therapy in allogeneic hematopoietic stem cell transplantation in hepatitis B virus patients
Ya-Ping Liao, Jia-Lu Jiang, Wai-Yi Zou, Duo-Rong Xu, Juan Li
Ya-Ping Liao, Jia-Lu Jiang, Wai-Yi Zou, Duo-Rong Xu, Juan Li, Department of Hematology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
Author contributions: Zou WY and Li J designed the study and wrote the protocol; Zou WY and Liao YP designed the study and helped with all correspondence related to this paper; Zou WY and Liao YP instructed the whole study and manuscript writing; Liao YP, Jiang JL and Xu DR performed experimental studies; Liao YP and Jiang JL acquired the data; Liao YP managed the literature searches and analyses as well as the statistical analysis; Liao YP wrote the first draft of the manuscript; all the authors approved the final version of the manuscript.
Ethics approval: The study was reviewed and approved by Institutional Review Board of the First Affiliated Hospital, Sun Yat-sen University.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: No potential conflicts of interest relevant to this article were reported.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wai-Yi Zou, Associate Professor, Department of Hematology, the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510000, Guangdong Province, China. waiyizou@medmail.com.cn
Telephone: +86-20-28823388
Received: August 25, 2014
Peer-review started: August 26, 2014
First decision: September 27, 2014
Revised: November 19, 2014
Accepted: January 8, 2015
Article in press: January 8, 2015
Published online: April 14, 2015
Abstract

AIM: To investigate the timing, safety and efficacy of prophylactic antiviral therapy in patients with hepatitis B virus (HBV) infection undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODS: This prospective study recruited a total of 57 patients diagnosed with malignant hematological diseases and HBV infection at the First Affiliated Hospital of Sun Yat-sen University between 2006 and 2013. The patients were classified as hepatitis B surface antigen (HBsAg)-positive or HBsAg-negative/ antiHBc-positive. Patients were treated with chemotherapy followed by antiviral therapy with nucleoside analogues. Patients underwent allo-HSCT when serum HBV DNA was < 103 IU/mL. Following allo-HSCT, antiviral therapy was continued for 1 year after the discontinuation of immunosuppressive therapy. A total of 105 patients who underwent allo-HSCT and had no HBV infection were recruited as controls. The three groups were compared for incidence of graft-vs-host disease (GVHD), drug-induced liver injury, hepatic veno-occlusive disease, death and survival time.

RESULTS: A total of 29 of the 41 subjects with chronic GVHD exhibited extensive involvement and 12 exhibited focal involvement. Ten of the 13 subjects with chronic GVHD in the HBsAg(-)/hepatitis B core antibody(+) group exhibited extensive involvement and 3 exhibited focal involvement. Five of the 10 subjects with chronic GVHD in the HBsAg(+) group exhibited extensive involvement and 5 exhibited focal involvement. The non HBV-infected group did not differ significantly from the HBsAg-negative/antiHBc-positive and the HBsAg-positive groups which were treated with nucleoside analogues in the incidence of graft-vs-host disease (acute GVHD; 37.1%, 46.9% and 40%, respectively; P = 0.614; chronic GVHD; 39%, 40.6% and 40%, respectively; P = 0.98), drug-induced liver injury (25.7%, 18.7% and 28%, respectively; P = 0.7), death (37.1%, 40.6% and 52%, respectively; P = 0.4) and survival times (P = 0.516). One patient developed HBV reactivation (HBsAg-positivity) due to early discontinuation of antiviral therapy.

CONCLUSION: Suppression of HBV DNA to < 103 IU/mL before transplantation, continued antiviral therapy and close monitoring of immune markers and HBV DNA after transplantation may assure the safety of allo-HSCT.

Keywords: Hematopoietic stem cell transplantation, Hepatitis B virus, Antiviral therapy, Nucleotide analogues

Core tip: The threshold of pre-transplantation hepatitis B virus (HBV) DNA for allo-HSCT was defined as 103 IU/mL. Only 1 patient developed HBV reactivation due to early discontinuation of antiviral therapy. The hepatitis B surface antigen (HBsAg)(+), HBsAg(-)/hepatitis B core antibody(+) and non-HBV infected groups showed no statistically significant differences in the incidence of graft-vs-host disease, drug-induced liver injury, hepatic veno-occlusive disease death, survival times and post-transplantation cumulative survival rates. In summary, suppression of HBV DNA to < 103 IU/mL before transplantation, continued antiviral therapy and close monitoring of immune markers of hepatitis B and HBV DNA after transplantation may assure the safety of allogeneic hematopoietic stem cell transplantation.