Blood Res.  2024;59:31. 10.1007/s44313-024-00035-5.

Hepatitis B surface antigen reverse seroconversion after hematopoietic stem cell transplantation according to the baseline serological marker levels and vaccination status: a single‑center database analysis

• Kang S
• Ko H
• Lee R
• Park S
• Han S

• KMID: 2562535
• DOI: http://doi.org/10.1007/s44313-024-00035-5

Abstract

Purpose
Hepatitis B is a major prognostic factor after hematopoietic stem cell transplantation (HSCT). Currently, no consensus exists regarding the management of various scenarios that can lead to reverse seroconversion of the hepatitis B surface antigen (HBsAg-RS). This study focused on HBsAg-RS, which serves as an indicator of active hepatitis, and aimed to obtain exploratory information on the associated patient and treatment factors.
Methods
This single-center retrospective study utilized clinical data extracted from the electronic medical records of Seoul St. Mary’s Hospital, Korea. Patients who underwent HSCT between January 2013 and December 2018 and tested negative for hepatitis B surface antigen (HBsAg) before undergoing HSCT were included. The associations between HBsAg-RS and demographic information, baseline hepatitis B serological markers, and vaccination status were statistically analyzed.
Results
This study included 1,344 patients, of whom 83.3% tested positive for the hepatitis B surface antibody (HBsAb) during HSCT. HBsAg-RS occurred in 2.2% of HBsAb-negative patients and 3.0% of HBsAb-positive patients, indicating no significant difference in reactivation rates according to HBsAb status. However, positivity for hepatitis B core antibody (HBcAb) was significantly associated with hepatitis B reactivation (HBsAg-RS rate: 8.0%). The vaccination rates were highest in patients who were negative for both HBsAb and HBcAb and had a transient protective effect.
Conclusion
The sufficient patient population enabled the identification of an association between baseline HBcAb positivity and the development of HBsAg-RS. Further prospective studies are warranted to determine optimal vac‑ cination strategies for preventing HBsAg-RS.

Keyword

Hematopoietic Stem Cell Transplantation; Hepatitis B Prophylaxis; Reverse Seroconversion; Retrospective; Vaccination

Figure

• 

  Fig. 1 Flow diagram of the participant selection process. Abbreviations: HBsAb, hepatitis B surface antibody; HSCT, hematopoietic stem cell transplantation; EMR, electronic medical record

• 

  Fig. 2 Cumulative incidence of reverse seroconversion after HSCT in unvaccinated (red line) and vaccinated (green line) patients: (A) All patients, (B) HBcAb-positive and HBsAb-positive patients, and (C) HBcAb-positive and HBsAb-negative patients. Abbreviations: HBV, hepatitis B virus; HBsAb, hepatitis B surface antibody; HBcAb, hepatitis B core antibody; HSCT, hematopoietic stem cell transplantation; HR, hazard ratio; CI, confidence interval

Reference

1. Anastasiou OE, Almpani F, Herrmann A, Gerken G, Ditschkowski M, Ciesek S. 2017; HBV reactivation in allogeneic stem cell transplant recipients: risk factors, outcome, and role of hepatitis B virus mutations. Hepatol Commun. 1:1014–23. https://doi.org/10.1002/hep4.1118. DOI: 10.1002/hep4.1118. PMID: 29404439. PMCID: PMC5721402.

2. Chaichotjinda K, Anurathapan U, Boonsathorn S, Chaisavaneeyakorn S, Treepongkaruna S, Techasaensiri C, Apiwattanakul N. 2020; Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients. Clin Transplant. 34:e14024. https://doi.org/10.1111/ctr.14024. DOI: 10.1111/ctr.14024.

3. Chen MH, Lee IC, Chen MH, Hou MC, Tsai CY, Huang YH. 2021; Abatacept is second to rituximab at risk of HBsAg reverse seroconversion in patients with rheumatic disease. Ann Rheum Dis. 80:1393–9. https://doi.org/10.1136/annrheumdis-​2021-220774. DOI: 10.1136/annrheumdis-2021-220774. PMID: 34187776.

4. Cho SY, Lee HJ, Lee DG. 2018; Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea. Korean J Intern Med. 33:256–76. https://doi.org/10.3904/kjim.2018.036. DOI: 10.3904/kjim.2018.036. PMID: 29506345. PMCID: PMC5840605.

5. Hur YJ, Choe SA, Choe YJ, Paek J. 2021; Hepatitis B surface antigen and antibody positivity among women of childbearing age after three decades of universal vaccination in South Korea. Int J Infect Dis. 104:551–5. https://doi.org/10.1016/j.ijid.2020.11.147. DOI: 10.1016/j.ijid.2020.11.147.

6. Jun CH, Kim BS, Oak CY, Lee DH, Cho E, Cho SB, Choi SK, Park CH, Joo YE, Lee JJ, Kim HJ. 2017; HBV reactivation risk factors in patients with chronic HBV infection with low replicative state and resolved HBV infection undergoing hematopoietic stem cell transplantation in Korea. Hepatol Int. 11:87–95. https://doi.org/10.1007/s12072-​016-​9747-0. DOI: 10.1007/s12072-016-9747-0.

7. Kim H, Sim M, Jahng S, Jeong J, Lee S, Son H. 2019; Seroprevalence of surface antigen and antibody positive rate of hepatitis b virus in low-income people. Korean J Fam Pract. 9:185–9. https://doi.org/10.21215/kjfp.2019.9.2.185. DOI: 10.21215/kjfp.2019.9.2.185.

8. Gentile G, Andreoni M, Antonelli G, Sarmati L. 2017; Screening, monitoring, prevention, prophylaxis and therapy for hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation: a systematic review. Clin Microbiol Infect. 23:916–23. https://doi.org/10.1016/j.cmi.2017.06.024. DOI: 10.1016/j.cmi.2017.06.024.

9. Hammond SP, Ho VT, Marty FM. 2022; Hepatitis B virus vaccination after allogeneic hematopoietic cell transplantation prevents post-transplantation hepatitis B virus reactivation. Transplant Cell Ther. 28(402):e1–402.e5. https://doi.org/10.1016/j.jtct.2022.04.004. DOI: 10.1016/j.jtct.2022.04.004.

10. Kim J, Chung SJ, Sinn DH, Lee KW, Park JB, Huh W, Lee JE, Jang HR, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. 2020; Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigennegative, core antibody-positive recipients. J Viral Hepat. 27:739–46. https://doi.org/10.1111/jvh.13279. DOI: 10.1111/jvh.13279.

11. Knöll A, Boehm S, Hahn J, Holler E, Jilg W. 2004; Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 33:925–9. https://doi.org/10.1038/sj.bmt.1704457. DOI: 10.1038/sj.bmt.1704457.

12. Li Z, Rubinstein SM, Thota R, Savani M, Brissot E, Shaw BE, Majhail NS, Mohty M, Savani BN. 2016; Immune-mediated complications after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 22:1368–75. https://doi.org/10.1016/j.bbmt.2016.04.005. DOI: 10.1016/j.bbmt.2016.04.005. PMID: 27095688.

13. Murt A, Elverdi T, Eskazan AE, Salihoglu A, Ar MC, Ongoren S, Baslar Z, Soysal T. 2020; Hepatitis B reactivation in hematopoietic stem cell transplanted patients: 20 years of experience of a single center from a middle endemic country. Ann Hematol. 99:2671–7. https://doi.org/10.1007/s00277-​020-​04206-z. DOI: 10.1007/s00277-020-04206-z. PMID: 32737632.

14. Nishikawa K, Kimura K, Kanda Y, Sugiyama M, Kakihana K, Doki N, Ohashi K, Bae SK, Takahashi K, Ishihara Y, Mizuno I, Onishi Y, Onozawa M, Onizuka M, Yamamoto M, Ishikawa T, Inoue K, Kusumoto S, Hashino S, Saito H, Kanto T, Sakamaki H, Mizokami M. 2020; A prospective trial of vaccine to prevent hepatitis B virus reactivation after hematopoietic stem cell transplantation. Bone Marrow Transplant. 55:1388–98. https://doi.org/10.1038/s41409-​020-​0833-5. DOI: 10.1038/s41409-020-0833-5. PMID: 32071416. PMCID: PMC7329632.

15. Onozawa M, Hashino S, Izumiyama K, Kahata K, Chuma M, Mori A, Kondo T, Toyoshima N, Ota S, Kobayashi S, Hige S, Toubai T, Tanaka J, Imamura M, Asaka M. 2005; Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection. Transplantation. 79:616–9. https://doi.org/10.1097/01.tp.0000151661.52601.fb. DOI: 10.1097/01.TP.0000151661.52601.FB. PMID: 15753855.

16. Pawłowska M, Flisiak R, Gil L, Horban A, Hus I, Jaroszewicz J, Lech-Marańda E, Styczyński J. 2019; Prophylaxis of hepatitis B virus (HBV) infection reactivation -recommendations of the Working Group for prevention of HBV reactivation. Clin Exp Hepatol. 5:195–202. https://doi.org/10.5114/ceh.2019.87631. DOI: 10.5114/ceh.2019.87631.

17. Shouval D, Shibolet O. 2013; Immunosuppression and HBV reactivation. Semin Liver Dis. 33:167–77. https://doi.org/10.1055/s-​0033-​1345722. DOI: 10.1055/s-0033-1345722.

18. Hsiao LT, Chiou TJ, Gau JP, Yang CF, Yu YB, Liu CY, Liu JH, Chen PM, Tzeng CH, Chan YJ, Yang MH, Huang YH. 2015; Risk of reverse seroconversion of hepatitis B virus surface antigen in rituximab-treated non-Hodgkin lymphoma patients: a large cohort retrospective study. Medicine (Baltimore). 94:e1321. https://doi.org/10.1097/MD.0000000000001321. DOI: 10.1097/MD.0000000000001321. PMID: 26266374. PMCID: PMC4616669.