Clearance of hepatitis B surface antigen (HBsAg) is an ideal therapeutic goal for patients with chronic hepatitis B virus (HBV) infection. Haematopoietic stem cell transplantation (HSCT) is the most effective therapy for a variety of haematological diseases. For patients with chronic HBV infection who received allo-HSCT, recipient hepatitis B serological status might change after allo-HSCT; however, data on the loss of HBsAg following allo-HSCT are relatively rare. We first reviewed patients with chronic HBV infection who received allo-HSCT in our centre from 2010 to 2020, and 125 patients were included in our study. A total of 62 patients (49.6%) with chronic HBV infection achieved HBsAg loss after allo-HSCT. Positivity for HBeAb and HBsAb in donors as well as no cytomegalovirus (CMV) infection were identified as independent risk factors for HBsAg loss after allo-HSCT. A predictive model including positivity for HBeAb and HBsAb in donors and no CMV infection was subsequently developed and performed well with effective discrimination and calibration. In addition, patients could benefit when this model is used in the clinic, as revealed via decision-curve analysis (DCA). However, multicentre prospective studies are required for validation.
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Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30:2212–9.
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015;386:1546–55.
Ozakyol A. Global epidemiology of Hepatocellular Carcinoma (HCC Epidemiology). J Gastrointest Cancer 2017;48:238–40.
Chu CM, Liaw YF. HBsAg seroclearance in Asian patients: too high and too bad in Hong Kong. Gastroenterology 2009;136:1459–60. 1460-1.
Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70:361–70.
Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009;50:1084–92.
EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.
Alawad AS, Auh S, Suarez D, Ghany MG. Durability of spontaneous and treatment-related loss of Hepatitis B s antigen. Clin Gastroenterol H 2020;18:700–9.
Marcellin P, Wong DK, Sievert W, Buggisch P, Petersen J, Flisiak R, et al. Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection. Liver Int. 2019;39:1868–75.
Marcellin P, Buti M, Krastev Z, de Man RA, Zeuzem S, Lou L, et al. Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. J Hepatol. 2014;61:1228–37.
Yu C, Sun Y, Xu L, Zhang X, Liu K, Jin J, et al. Hepatitis B seropositive status in recipients or donors is not related to worse outcomes after haploidentical hematopoietic stem cell transplantation. Transpl Cell Ther 2021;27:661–8.
Buzo BF, Ramos JF, Marques Rossetti RA, Salles N, Mendrone Júnior A, Rocha V, et al. Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center. Transpl Infect Dis. 2020;22:e13243.
Francisci D, Aversa F, Coricelli V, Carotti A, Canovari B, Falcinelli F, et al. Prevalence, incidence and clinical outcome of hepatitis B virus and hepatitis C virus hepatitis in patients undergoing allogeneic hematopoietic stem cell transplantation between 2001 and 2004. Haematologica. 2006;91:980–2.
Park S, Kim K, Kim DH, Jang JH, Kim SJ, Kim WS, et al. Changes of hepatitis B virus serologic status after allogeneic hematopoietic stem cell transplantation and impact of donor immunity on hepatitis B virus. Biol Blood Marrow Transpl. 2011;17:1630–7.
Lau GK, Lok AS, Liang RH, Lai CL, Chiu EK, Lau YL, et al. Clearance of hepatitis B surface antigen after bone marrow transplantation: role of adoptive immunity transfer. Hepatology 1997;25:1497–501.
Chang YJ, Huang XJ. Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review. Clin Transpl. 2011;25:13–23.
Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer-Am Cancer Soc. 2013;119:978–85.
Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transpl. 2006;38:291–7.
Yan CH, Xu LP, Wang FR, Chen H, Han W, Wang Y, et al. Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation. Bone Marrow Transpl. 2016;51:391–7.
Lok AS, Zoulim F, Dusheiko G, Chan HLY, Buti M, Ghany MG, et al. Durability of Hepatitis B surface antigen loss with nucleotide analogue and peginterferon therapy in patients with chronic Hepatitis B. Hepatol Commun 2020;4:8–20.
Li M, Zhang L, Lu Y, Chen Q, Lu H, Sun F, et al. Early serum HBsAg kinetics as predictor of HBsAg loss in patients with HBeAg-negative chronic Hepatitis B after treatment with Pegylated Interferonα-2a. Virol Sin. 2021;36:311–20.
Terrault NA, Lok ASF, McMahon BJ, Chang K, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560–99.
Yang Y, Huang A, Zhao Y. Spontaneous loss of chronic HBV infection markers in treatment-naïve children: a systematic review and pooled meta-analyses. Expert Rev Anti-Infe. 2021;19:649–60.
Cao Z, Li Z, Wang Y, Liu Y, Mo R, Ren P, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection. J Viral Hepat. 2017;24(Suppl 1):57–65.
Shi Y, Zheng M. Hepatitis B virus persistence and reactivation. BMJ. 2020;370:m2200.
Hui CK, Lie A, Au WY, Leung YH, Ma SY, Cheung WW, et al. A long-term follow-up study on hepatitis B surface antigen-positive patients undergoing allogeneic hematopoietic stem cell transplantation. Blood 2005;106:464–9.
Wu Y, Shi J, Tan Y, Zhao Y, Yu J, Lai X, et al. A novel strategy for the prevention of Hepatitis B virus-related hepatitis following allogeneic hematopoietic stem cell transplantation from Hepatitis B surface antigen-positive donors. Biol Blood Marrow Transpl. 2020;26:1719–28.
Sullivan LM, Massaro JM, D’Agostino RS. Presentation of multivariate data for clinical use: The Framingham Study risk score functions. Stat Med. 2004;23:1631–60.
Ren X, Huang Q, Qu Q, Cai X, Fu H, Mo X, et al. Predicting mortality from intracranial hemorrhage in patients who undergo allogeneic hematopoietic stem cell transplantation. Blood Adv. 2021;5:4910–21.
Deng RX, Wu YJ, Xu LP, Liu KY, Huang XJ, Zhang XH. Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies. Am J Hematol. 2021;96:1407–19.
Gui RY, Huang QS, Cai X, Wu J, Liu HX, Liu Y, et al. Development and validation of a prediction model (AHC) for early identification of refractory thrombotic thrombocytopenic purpura using nationally representative data. Br J Haematol. 2020;191:269–81.
Pabinger I, van Es N, Heinze G, Posch F, Riedl J, Reitter EM, et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol 2018;5:e289–98.
Wu YJ, Hou M, Liu HX, Peng J, Ma LM, Yang LH, et al. A risk score for predicting hospitalization for community-acquired pneumonia in ITP using nationally representative data. Blood Adv. 2020;4:5846–57.
Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making. 2006;26:565–74.
Vickers AJ, van Calster B, Steyerberg EW. A simple, step-by-step guide to interpreting decision curve analysis. Diagn Progn Res 2019;3:18.
Lavezzi M, Donati A, Davi D, Carpanelli MC, Farinelli S, Soracco E. [Response to vaccination against the etiologic agent of viral hepatitis B (HBV) in a population at risk]. Quad Sclavo Diagn. 1987;23:164–8.
McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009;49(5 Suppl):S45–55.
Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736–88.
Liu JH, Liao XW, Chen CH, Yao M, Li CC, Lin CT, et al. Adoptive donor immunity protects against resolved hepatitis B virus reactivation after allogeneic haematopoietic stem cell transplantation in the world’s largest retrospective cohort study. Brit J Haematol. 2019;186:72–85.
Mikulska M, Nicolini L, Signori A, Rivoli G, Del BV, Raiola AM, et al. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome. Clin Microbiol Infect. 2014;20:O694–701.
Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, et al. Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a increases loss of Hepatitis B surface antigen in patients with chronic hepatitis B. Gastroenterology 2016;150:134–44.
Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: From discovery to regulatory approval. Hepatology 2017;66:1296–313.
Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HLA, Chan HL. The role of quantitative hepatitis B surface antigen revisited. J Hepatol. 2016;66:398–411.
Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Wang LY, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2010;139:474–82.
Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, et al. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study. J Gastroenterol. 2013;48:930–41.
Seto W, Chan TS, Hwang Y, Wong DK, Fung J, Liu KS, et al. Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study. Hepatology 2017;65:1451–61.
Gentile G, Antonelli G. HBV Reactivation in patients undergoing hematopoietic stem cell transplantation: a narrative review. Viruses. 2019;11.
Ljungman P, de la Camara R, Robin C, Crocchiolo R, Einsele H, Hill JA, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis 2019;19:e260–72.
Harvala H, Stewart C, Muller K, Burns S, Marson L, MacGilchrist A, et al. High risk of cytomegalovirus infection following solid organ transplantation despite prophylactic therapy. J Med Virol. 2013;85:893–8.
Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation. Hematol/Oncol Stem Cell Ther 2017;10:233–8.
Meesing A, Razonable RR. New developments in the management of cytomegalovirus infection after transplantation. DRUGS 2018;78:1085–103.
Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica 2016;101:803–11.
Ocheni S, Kroeger N, Zabelina T, Sobottka I, Ayuk F, Wolschke C, et al. EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT. Bone Marrow Transpl. 2008;42:181–6.
Jackson SE, Redeker A, Arens R, van Baarle D, van den Berg S, Benedict CA, et al. CMV immune evasion and manipulation of the immune system with aging. Geroscience 2017;39:273–91.
Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Infect Dis Clin North Am. 2010;24:319–37.
Chaichotjinda K, Anurathapan U, Boonsathorn S, Chaisavaneeyakorn S, Treepongkaruna S, Techasaensiri C, et al. Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients. Clin Transpl. 2020;34:e14024.
Sun X, Su Y, Liu X, Zhang Y, He Y, Han W, et al. Overt gastrointestinal bleeding following haploidentical haematopoietic stem cell transplantation: incidence, outcomes and predictive models. Bone Marrow Transpl. 2021;56:1341–51.
This work was supported by the National Key Research and Development Program of China. (Nos. 2017YFA0105500 and 2017YFA0105503), the National Natural Science Foundation of China (No. 81970113), the Key Program of National Natural Science Foundation of China (No. 81730004) and the Beijing Natural Science Foundation (No. H2018206423).
The authors declare no competing interests.
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Sun, X., Fu, H., Wang, C. et al. Predicting the loss of hepatitis B surface antigen following haematopoietic stem cell transplantation in patients with chronic HBV infection. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01880-7