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Abstract Details
Hepatitis B Virus Reactivation Associated with New Classes of Immunosuppressants and Immunomodulators: A Systematic Review, Meta-analysis, and Expert Opinion
J Hepatol. 2022 Jul 15;S0168-8278(22)02935-X. doi: 10.1016/j.jhep.2022.07.003.Online ahead of print.
1Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
2Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece. Electronic address: reddyr@pennmedicine.upenn.edu.
3Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
4Division of Hepatology, Department of Medicine, Leipzig University Hospital, Leipzig, Germany.
5Division of Gastroenterology and Hepatology, Union Hospital and Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
6Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
7Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA.
8Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: aslok@med.umich.edu.
9Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Electronic address: reddyr@pennmedicine.upenn.edu.
Abstract
Background: Hepatitis B reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NA). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed a guidance for NA prophylaxis.
Methods: A Medline and EMBASE database search was conducted on studies pertaining to 19 classes of immunosuppressive or immunomodulatory therapies published between 2010-2021. The outcomes of interest were incidence of HBVr with or without biochemical exacerbation. Pooled rates were calculated by generalized linear mixed models if there were ≥3 studies with available data. An expert panel reviewed the data and categorized the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%).
Results: 1752 studies resulted from our search, of which 59 including 3424 HBsAg+ and 5799 HBsAg-/anti-HBc+ patients met eligibility criteria. Immune check point inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor (CAR) T-cell immunotherapies, and corticosteroids were categorized as high HBVr risk in HBsAg+ patients; cytokine inhibitors, CAR T-cell immunotherapies, and corticosteroids as intermediate risk in HBsAg-/anti-HBc+ patients; and anti-TNF agents and immune check point inhibitors as low risk in HBsAg-/anti-HBc+ patients; based on medium-high quality evidence. Provisional recommendation was provided for drugs with low quality evidence. NA prophylaxis is recommended when drugs with high HBVr risk are used and monitoring and on-demand NA for drugs with low risk, while either approach may be appropriate for drugs with intermediate risk.
Conclusion: Consensus on definition and methods of reporting HBVr along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials are needed to provide reliable data on HBVr risk associated with immunosuppressive or immunomodulatory therapies.