Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;15(5):1031-1048.
doi: 10.1007/s12072-021-10239-x. Epub 2021 Aug 24.

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

George Lau  1   2 , Ming-Lung Yu  3 , Grace Wong  4 , Alexander Thompson  5 , Hasmik Ghazinian  6 , Jin-Lin Hou  7 , Teerha Piratvisuth  8 , Ji-Dong Jia  9 , Masashi Mizokami  10 , Gregory Cheng  11   12 , Guo-Feng Chen  13 , Zhen-Wen Liu  14 , Oidov Baatarkhuu  15 , Ann Lii Cheng  16 , Woon Leung Ng  17 , Patrick Lau  18 , Tony Mok  19 , Jer-Ming Chang  20 , Saeed Hamid  21 , A Kadir Dokmeci  22 , Rino A Gani  23 , Diana A Payawal  24 , Pierce Chow  25 , Joong-Won Park  26 , Simone I Strasser  27 , Rosmawaiti Mohamed  28 , Khin Maung Win  29 , Tanwandee Tawesak  30 , Shiv Kumar Sarin  31 , Masao Omata  32   33
Affiliations

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

George Lau et al. Hepatol Int. 2021 Oct.

Erratum in

Abstract

Background & aim: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation.

Methods: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation.

Recommendations: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

Keywords: APASL; Guideline; Hepatitis B reactivation; Immunosuppressive therapy.

PubMed Disclaimer

Conflict of interest statement

Ming-Lung Yu received research grants from Abbott, BMS, Gilead and Merck and received fees for being a speaker/consultant from Abbvie, Abbott, BMS, Gilead, Merck, Ipsen and Roche. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen and Roche, and received research grant from Gilead Sciences. Alexander Thompson has served as an advisory committee member for Gilead Sciences, Abbvie, Roche, BMS, Merck, Immunocore, Janssen, Assembly Biosciences, Arbutus, Eisai, Ipsen and Bayer, as a speaker for Gilead Sciences, Abbvie, Roche, BMS, and received research grant from Gilead Sciences, Merck, BMS, Abbvie. Jin-Lin Hou received grants and personal fees from Bristol-Myers Squibb during the conduct of the study, and grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Teerha Piratvisuth received fees for being a speaker and advisory board member from Bayer, BMS, Gilead Sciences, and Eisai and received research support from Fibrogen, Gilead Sciences, Janssen and Roche. Ji-Dong Jia received consultation and speaker fees from Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme, Novartis, and Roche. Ann-Lii Cheng received consultant fees from Novartis, Merck Serono, Eisai, Merck Sharp and Dohme, ONXEO, Bayer, Bristol-Myers Squibb, and Ono Pharmaceutical. Tony Mok received fees for being a speaker, consultant, and advisory board member from AstraZeneca, Roche/Genentech, Lilly, Bristol Myers Squibb, Boehringer Ingelheim, Novartis, Merck Sharp & Dohme, Pfizer, Merck Serono, SFJ Pharmaceuticals Group, ACEA Biosciences, Vertex, Celgene, Ignyta, Fishawack Facilitate Ltd, Takeda, Janssen, Hutchison MediPharma, and received grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Group, Roche, Merck Sharp & Dohme, Clovis Oncology, Bristol Myers Squibb, Xcovery. Diana A. Payawal has served as an advisory committee member for Mylan Pharmaceutical, as a speaker for Gilead Sciences, Mylan Pharmaceuticals, Echosense, Getz and Abbott. Tawesak Tanwandee received grants from Bristol-Myers Squibb and Merck. Masao Omata received fees for being a speaker, consultant, and advisory board member from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Otsuka, Astellas, Gilead Sciences, Chugai, Mitsubishi Tanabe, Kyorin, Merck Sharp and Dohme, Dainippon Sumitomo, Vertex Pharmaceuticals, Takeda, Merck Serono, and Zeria. George Lau, Hasmik Ghazinian, Masashi Mizokami, Gregory Cheng, Guo-Feng Chen, Zhen-Wen Liu, Oidov Baatarkhuu, Woon Leung Ng, Patrick Lau, Jer-Ming Chang, Saeed Hamid, A. Kadir Dokmeci, Rino A Gani, Diana A. Payawal, Pierce Chow, Joong-Won Park, Simone I Strasser, Rosmawaiti Mohamed, Khin Maung Win, Shiv Kumar Sari declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Pathogenesis of hepatitis due to hepatitis B virological reactivation (HBVr). Hepatitis due to HBVr is a two-phase process with an initial phase of enhanced HBV replication and hepatocyte expression of HBV antigen due to attenuation of host immunity against HBV. The use of steroid could further augment viral replication due to its effect on steroid-responsive elements in HBV. Attenuation of host immunity against HBV replication can also be related to removal of hyperactive innate immunity with DAA therapy against co-infected HCV. The second phase is characterized by immune reconstitution on withdrawal of immunosuppressive effect on HBVr due to withdrawal of the immunosuppressive therapy or continuous rapid suppression of HCV by DAAs. This will initiate the mounting of host immune response against heavily HBV antigen-laden hepatocyte, resulting in liver injury, manifested as elevation of serum ALT with mild hepatitis, icteric hepatitis, hepatic failure or even death
Fig. 2
Fig. 2
Algorithm for the management of hepatitis B reactivation. All high-risk patients and moderate risk HBsAg + patients should be treated with pre-emptive NUCs irrespective of fibrosis status. All patients with advanced fibrosis or cirrhosis should be treated with NUCs irrespective risk stratifications. All HBsAg + patients should be treated with NUCs except for low-risk patients without advanced fibrosis or cirrhosis. Low-risk HBsAg + without advanced fibrosis or cirrhosis should be monitored with ALT testing every three months. Moderate and low risks HBsAg − anti-HBc + patients without advanced fibrosis or cirrhosis should be monitored with ALT testing every three months
See this image and copyright information in PMC

Comment in

References

    1. Wands JR, Chura CM, Roll FJ, Maddrey WC. Serial studies of hepatitis-associated antigen and antibody in patients receiving antitumor chemotherapy for myeloproliferative and lymphoproliferative disorders. Gastroenterology. 1975;68(1):105–112. - PubMed
    1. Hoofnagle JH, Dusheiko GM, Schafer DF, Jones EA, Micetich KC, Young RC, Costa J. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med. 1982;96(4):447–449. - PubMed
    1. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology. 1991;100(1):182–188. - PubMed
    1. Lau G, Liang R, Chiu EK, Lee CK, Lam SK. Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study. Bone Marrow Transplant. 1997;19(8):795–799. - PubMed
    1. Lau G. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int. 2008;2(2):152–162. - PMC - PubMed

Substances