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01-03-2022 | Hepatitis B | Original Article

Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area

Authors: Yibo Wu, Yi Chen, Panpan Zhu, Baodong Ye, Ying Lu, Jimin Shi, Yamin Tan, Yanmin Zhao, Jian Yu, Xiaoyu Lai, Jianping Lan, Ting Si, Lihong Ni, He Huang, Yi Luo

Published in: Annals of Hematology | Issue 3/2022

Abstract

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs–negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs–positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation.

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WHO. Global Hepatitis Report. Available online: https://www.who.int/hepatitis/publications/globalhepatitis-report2017 (accessed on 4 April 2019).

Y Luo H Xiao X Lai J Shi Y Tan J He 2014 T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT Blood 124 17 2735 2743 https://doi.org/10.1182/blood-2014-04-571570CrossRefPubMedPubMedCentral

Yi Luo, Mengqi Jin, Yamin Tan, Yanmin Z, Jimin S, Yuanyuan Z et al. Antithymocyte globulin improves GVHD-free and relapse-free survival in unrelated hematopoietic stem cell transplantation. Bone Marrow Transplantation 2019; 54(10):1668-1675. doi: https://doi.org/10.1038/s41409-019-0502-8

Lv Meng, Chang Ying-jun, xiao-jun H. Update of the "Beijing Protocol" haplo-identical hematopoietic stem cell transplantation. Bone Marrow Transplantation 2019; 54(Suppl 2): 703-707. doi: https://doi.org/10.1038/s41409-019-0605-2

D'Souza A, Fretham C, Lee SJ, Arora M, Brunner J, S C. Current use of and trends in hematopoietic cell transplantation in the United States. Biology of Blood and Marrow Transplantation 2020; 26(8): e177-e182. doi: https://doi.org/10.1016/j.bbmt.2020.04.013

GKK Lau M-L He DYT Fong A Bartholomeusz W-Y Au AKW Lie 2002 Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation Hepatology 36 3 702 709 https://doi.org/10.1053/jhep.2002.35068CrossRefPubMed

A Locasciulli B Bruno EP Alessandrino G Meloni W Arcese G Bandini 2003 Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation Bone Marrow Transplant 31 4 295 300 https://doi.org/10.1038/sj.bmt.1703826CrossRefPubMed

RP Perrillo R Gish YT Falck-Ytter 2015 American Gastroenterological Association Institute Technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy Gastroenterology 148 1 221 244.e223 https://doi.org/10.1053/j.gastro.2014.10.038 Epub 2014 Oct 31CrossRefPubMed

W-K Seto TS-Y Chan Y-Y Hwang DK-H Wong J Fung KS-H Liu 2017 Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: a prospective study Hepatology 65 5 1451 1461 https://doi.org/10.1002/hep.29022CrossRefPubMed

10.

K Kitano H Kobayashi M Hanamura K Furuta M Ueno A Rokuhara 2006 Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region Eur J Haematol 77 3 255 258 https://doi.org/10.1111/j.1600-0609.2006.00678.xCrossRefPubMed

11.

JP Hwang MJ Fisch Z Hong MA Kallen MJ Routbort LS Lal 2012 Low rates of hepatitis B virus screening at the onset of chemotherapy Journal of Oncology Practice 8 4 e32 39 https://doi.org/10.1200/JOP.2011.000450CrossRefPubMedPubMedCentral

12.

GKK Lau HHY Yiu DYT Fong H-C Cheng W-Y Au LSF Lai 2003 Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy Gastroenterology 125 6 1742 1749 https://doi.org/10.1053/j.gastro.2003.09.026CrossRefPubMed

13.

C Hsu CA Hsiung I-J Su W-S Hwang M-C Wang S-F Lin 2008 A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial Hepatology 47 3 844 853 https://doi.org/10.1002/hep.22106CrossRefPubMed

14.

Y-P Liao J-L Jiang W-Y Zou D-R Xu J Li 2015 Prophylactic antiviral therapy in allogeneic hematopoietic stem cell transplantation in hepatitis B virus patients World J Gastroenterol 21 14 4284 4292CrossRef

15.

J Aoki K Kimura K Kakihana K Ohashi H Sakamaki 2014 Efficacy and tolerability of entecavir for hepatitis B virus infection after hematopoietic stem cell transplantation Springerplus 20 3 450 https://doi.org/10.1186/2193-1801-3-450CrossRef

16.

A Siyahian SU Malik A Mushtaq CL Howe A Majeed T Zangeneh 2018 Prophylaxis for hepatitis B virus reactivation after allogeneic stem cell transplantation in the era of drug resistance and newer antivirals: a systematic review and meta-analysis Biology of Blood and Marrow Transplantation 24 7 1483 1489 https://doi.org/10.1016/j.bbmt.2018.02.027CrossRefPubMedPubMedCentral

17.

L-T Hsiao T-J Chiou J-H Liu C-J Chu Y-C Lin T-C Chao 2006 Extended lamivudine therapy against hepatitis B virus infection in hematopoietic stem cell transplant recipients Biol Blood Marrow Transplant 12 1 84 94 https://doi.org/10.1016/j.bbmt.2005.09.001CrossRefPubMed

18.

J Shang H Wang J Sun Z Fan F Huang Y Zhang 2016 A comparison of lamivudine vs entecavir for prophylaxis of hepatitis B virus reactivation in allogeneic hematopoietic stem cell transplantation recipients: a single-institutional experience Bone Marrow Transplant 51 4 581 586 https://doi.org/10.1038/bmt.2015.328CrossRefPubMed

19.

G Gentile G Antonelli 2019 HBV reactivation in patients undergoing hematopoietic stem cell transplantation: a narrative review Viruses 11 11 1049 https://doi.org/10.3390/v11111049CrossRefPubMedCentral

20.

Y Wu H Huang Y Luo 2021 Management of hepatitis B virus in allogeneic hematopoietic stem cell transplantation Front Immunol 11 610500 https://doi.org/10.3389/fimmu.2020.610500CrossRefPubMedPubMedCentral

21.

A Zhang Y Wu Y Tan J Shi Y Zhao Y Hu 2020 Determining whether prophylactic antiviral treatment is necessary in HBsAg-negative/HBcAb-positive patients receiving allogeneic hematopoietic stem cell transplantation Biol Blood Marrow Transplant 26 5 956 964 https://doi.org/10.1016/j.bbmt.2020.01.006CrossRefPubMed

22.

P Ljungman M Boeckh HH Hirsch F Josephson J Lundgren G Nichols 2017 Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials Clin Infect Dis 64 1 87 91 https://doi.org/10.1093/cid/ciw668CrossRefPubMed

23.

MH Jagasia HT Greinix M Arora KM Williams D Wolff EW Cowen 2015 National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report Biology of Blood and Marrow Transplantation 21 3 389 401 https://doi.org/10.1016/j.bbmt.2014.12.001CrossRefPubMed

24.

NA Terrault ASF Lok BJ McMahon K-M Chang JP Hwang MM Jonas 2018 Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance Hepatology 67 4 4560 1599 https://doi.org/10.1002/hep.29800CrossRef

25.

A Visram JJ Feld 2015 Defining and grading HBV reactivation Clinical Liver Disease 25 2 35 38 https://doi.org/10.1002/cld.426CrossRef

26.

TA Gooley W Leisenring J Crowley BE Storer 1999 Estimation of failure probabilities in the presence of competing risks: new representations of old estimators Stat Med 18 6 695 706. https://doi.org/10.1002/(sici)1097-0258(19990330)18:6<695::aid-sim60>3.0.co;2-o

27.

L Scrucca A Santucci F Aversa 2007 Competing risk analysis using R: an easy guide for clinicians Bone Marrow Transplant 40 4 381 387 https://doi.org/10.1038/sj.bmt.1705727CrossRefPubMed

28.

JP Fine RJ Gray 1999 A Proportional hazards model for the subdistribution of a competing risk Publ Am Stat Assoc 94 446 496 509 https://doi.org/10.1080/01621459.1999.10474144CrossRef

29.

BW Teh MA Slavin J Szer JJ Sasadeusz 2013 Hepatitis B serological changes following allogeneic bone marrow transplantation Transplant Infectious Disease 15 1 98 103CrossRef

30.

C-K Hui A Lie W-Y Au Y-H Leung S Ma W Cheung 2005 A long-term follow-up study on hepatitis B surface antigen-positive patients undergoing allogeneic hematopoietic stem cell transplantation Blood 106 2 464 469 https://doi.org/10.1182/blood-2005-02-0698CrossRefPubMed

31.

RG Gish TT Chang CL Lai RD Man A Gadano F Poordad 2010 Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-nave HBeAg-positive patients with chronic hepatitis B J Viral Hepatitis 17 1 16 22 https://doi.org/10.1111/j.1365-2893.2009.01146.xCrossRef

32.

Y Ilan A Nagler R Adler E Naparstek R Or S Slavin 1993 Adoptive transfer of immunity to hepatitis B virus after T cell-depleted allogeneic bone marrow transplantation Hepatology 18 2 246 252PubMed

33.

A Guerrero SR Riddell J Storek T Stevens-Ayers B Storer JA Zaia 2011 Cytomegalovirus viral load and virus-specific immune reconstitution after peripheral blood stem cell versus bone marrow transplantation Biol Blood Marrow Transplant 18 1 66 75 https://doi.org/10.1016/j.bbmt.2011.05.010CrossRefPubMedPubMedCentral

34.

Y Ilan E Galun A Nagler Y Baruch N Livni R Tur-Kaspa 1996 Sanctuary of hepatitis B virus in bone-marrow cells of patients undergoing liver transplantation Liver Transpl Surg 2 3 206 210 https://doi.org/10.1002/lt.500020306CrossRefPubMed

35.

JH Liu XW Liao CH Chen M Yao CC Li CT Lin 2019 Adoptive donor immunity protects against resolved hepatitis B virus reactivation after allogeneic haematopoietic stem cell transplantation in the world's largest retrospective cohort study Br J Haematol 186 1 72 85 https://doi.org/10.1111/bjh.15884CrossRefPubMed

36.

Y Wang Q-F Liu R Lin T Yang Y-J Xu X-D Mo 2021 Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation: long-term follow-up of a multicenter, randomized controlled trial Science Bulletin https://doi.org/10.1016/j.scib.2021.06.002CrossRefPubMedPubMedCentral

37.

G Socié J Ritz 2014 Current issues in chronic graft-versus-host disease Blood 124 3 374 384 https://doi.org/10.1182/blood-2014-01-514752CrossRefPubMedPubMedCentral

38.

Y Chen L-P Xu K-Y Liu H Chen Y-H Chen X-H Zhang 2016 Risk factors for cytomegalovirus DNAemia following haploidentical stem cell transplantation and its association with host hepatitis B virus serostatus J Clin Virol 75 10 15 https://doi.org/10.1016/j.jcv.2015.12.003CrossRefPubMed

39.

Y-C Liu P-L Lu H-H Hsiao C-S Chang T-C Liu W-C Yang 2012 Cytomegalovirus infection and disease after allogeneic hematopoietic stem cell transplantation: experience in a center with a high seroprevalence of both CMV and hepatitis B virus Ann Hematol 91 4 587 595 https://doi.org/10.1007/s00277-011-1351-8CrossRefPubMed

40.

AMD Bisceglie AS Lok P Martin N Terrault RP Perrillo JH Hoofnagle 2015 Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: Just the tip of the iceberg? Hepatology 61 2 703 711 https://doi.org/10.1002/hep.27609CrossRefPubMed

41.

Liver. EAftSot. EASL 2017 2017 Clinical practice guidelines on the management of hepatitis B virus infection Journal of Hepatology 67 2 370 398 https://doi.org/10.1016/j.jhep.2017.03.021CrossRef

42.

L S, M A, G A, W A, R B, N C et al. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of Hepatitis B virus reactivation in patients with haematological malignancies and patients who underwent haematological stem cell transplantation - a position paper. Clinical Microbiology and Infection 2017; 23(12): 935-940. https://doi.org/10.1016/j.cmi.2017.06.023

43.

JHwang eP, Feld JJ, Hammond SP, Wang SH, Alston-Johnson DE, Cryer DR et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. Journal of Clinical Oncology 2020; 38(31): 3698-3715. doi: https://doi.org/10.1200/JCO.20.01757

44.

P Venessa 2016 Prevention of hepatitis B reactivation in the setting of immunosuppression Clin Mol Hepatol 22 2 219 237 https://doi.org/10.3350/cmh.2016.0024CrossRef

45.

Y Liu C Wang Y Zhong X Li J Dai X Ren 2011 Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection J Viral Hepatitis 18 4 e29 39 https://doi.org/10.1111/j.1365-2893.2010.01360.xCrossRef

46.

HL Lee JW Jang JW Han SW Lee SH Bae JY Choi 2019 Early hepatitis B surface antigen seroclearance following antiviral treatment in patients with reactivation of resolved hepatitis B Dig Dis Sci 64 10 2992 3000 https://doi.org/10.1007/s10620-019-05614-6CrossRefPubMed

Title: Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area
Authors: Yibo Wu
Yi Chen
Panpan Zhu
Baodong Ye
Ying Lu
Jimin Shi
Yamin Tan
Yanmin Zhao
Jian Yu
Xiaoyu Lai
Jianping Lan
Ting Si
Lihong Ni
He Huang
Yi Luo
Publication date: 01-03-2022
Publisher: Springer Berlin Heidelberg
Keywords: Hepatitis B
Graft-Versus-Host Disease
Entecavir
Lamivudine
Graft-Versus-Host Disease
Lamivudine
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: Annals of Hematology / Issue 3/2022
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-021-04730-6

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