Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay.
hepatitis B virus (HBV) reactivation
highly-sensitive hepatitis B core-related antigen assay (iTACT-HBcrAg)
nucleos(t)ide analogs (NA) treatment
resolved HBV infection
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
revised:
13
02
2022
received:
16
01
2022
accepted:
18
02
2022
pubmed:
25
2
2022
medline:
25
2
2022
entrez:
24
2
2022
Statut:
ppublish
Résumé
To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.
Types de publication
Journal Article
Langues
eng
Pagination
745-753Subventions
Organisme : Research Program on Hepatitis from the Japan Agency for Medical Research and Development: AMED JP21fk0310101 Ministry of Education, Culture, Sports, Science and Technology: JP19H03640) Scientific Research (C): JP20K08739
Informations de copyright
© 2022 Japan Society of Hepatology.
Références
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;100:182-8.
Dervite I, Hober D, Morel P. Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med. 2001;344:68-9.
Umemura T, Tanaka E, Kiyosawa K, Kumada H. Mortality secondary to fulminant hepatic failure in patients with prior resolution of hepatitis B virus infection in Japan. Clin Infect Dis. 2008;47:e52-6.
Seth P, Alrajhi AA, Kagevi I, Chaudhary M, Colcol E, Sahovic E, et al. Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease. Bone Marrow Transplant. 2002;30:189-94.
Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med. 1996;2:1104-8.
Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol. 2009;90:13-23.
Seto WK, Chan TS, Hwang YY, Wong DK-H, Fung J, Liu KS-H, et al. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol. 2014;32:3736-43.
Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H, et al. Monitoring of hepatitis B virus (HBV) DNA and risk of HBV reactivation in B-cell lymphoma: a prospective observational study. Clin Infect Dis. 2015;61:719-29.
Kusumoto S, Arcaini L, Hong X, Jin J, Kim WS, Kwong YL, et al. Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy. Blood. 2019;133:137-46.
Tamori A, Kimura K, Kioka K, Enomoto H, Odagiri N, Kozuka R, et al. Outcome of nucleos(t)ide analog intervention in patients with preventive or on-demand therapy for hepatitis B virus reactivation. J Med Virol. 2021;93:3679-87.
Seto WK, Cheung KS, Wong DK, Huang F-Y, Fung J, Liu KS-H, et al. Hepatitis B surface antigen seroclearance during nucleoside analogue therapy: surface antigen kinetics, outcomes, and durability. J Gastroenterol. 2016;51:487-95.
Hsu YC, Nguyen MH, Mo LR, Wu M-S, Yang T-H, Chen C-C, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49:107-15.
Sonneveld MJ, Park JY, Kaewdech A, et al. Prediction of sustained response after nucleo(s)tide analogue cessation using HBsAg and HBcrAg levels: a multicenter study (CREATE). Clin Gastroenterol Hepatol. 2020.
Tseng TN, Hu TH, Wang JH, Kuo Y-H, Hung C-H, Lu S-N, et al. Incidence and factors associated with HBV relapse after cessation of entecavir or tenofovir in patients with HBsAg below 100 IU/mL. Clin Gastroenterol Hepatol. 2020;18:2803-12.e2.
Inoue T, Tanaka Y. The role of hepatitis B core-related antigen. Genes. 2019:10.
Watanabe T, Inoue T, Tanaka Y. Hepatitis B core-related antigen and new therapies for hepatitis B. Microorganisms. 2021;9.
Inoue T, Matsui T, Tanaka Y. Novel strategies for the early diagnosis of hepatitis B virus reactivation. Hepatol Res. 2021;51:1033-43.
Inoue T, Kusumoto S, Iio E, Ogawa S, Suzuki T, Yagi S, et al. Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation. J Hepatol. 2021;75:302-10.
Suzuki F, Hosaka T, Imaizumi M, Kobayashi M, Ohue C, Suzuki Y, et al. Potential of ultra-highly sensitive immunoassays for hepatitis B surface and core-related antigens in patients with or without development of hepatocellular carcinoma after hepatitis B surface antigen seroclearance. Hepatol Res. 2021;51:426-35.
Drafting Committee for Hepatitis Management Guidelines tJSoH. Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection: 2019 update. Hepatol Res. 2020;50:892-923.
European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
Terrault NA, Lok ASF, McMahon BJ, Chang K-M, 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.