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1
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Xiong D, Cai W, Zhao W. Risk factors of HBV reactivation in leukemia patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation. Clin Res Hepatol Gastroenterol 2024; 48:102447. [PMID: 39181184 DOI: 10.1016/j.clinre.2024.102447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND The hepatitis B surface antigen (HBsAg)-negative and antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). METHODS To analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. RESULTS HBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. CONCLUSION The univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.
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Affiliation(s)
- Danping Xiong
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Wen Cai
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Weifeng Zhao
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
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2
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Kamboj M, Bohlke K, Baptiste DM, Dunleavy K, Fueger A, Jones L, Kelkar AH, Law LY, LeFebvre KB, Ljungman P, Miller ED, Meyer LA, Moore HN, Soares HP, Taplitz RA, Woldetsadik ES, Kohn EC. Vaccination of Adults With Cancer: ASCO Guideline. J Clin Oncol 2024; 42:1699-1721. [PMID: 38498792 PMCID: PMC11095883 DOI: 10.1200/jco.24.00032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 01/11/2024] [Indexed: 03/20/2024] Open
Abstract
PURPOSE To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. RECOMMENDATIONS The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell-depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine.Additional information is available at www.asco.org/supportive-care-guidelines.
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Affiliation(s)
- Mini Kamboj
- Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
| | - Kari Bohlke
- American Society of Clinical Oncology, Alexandria, VA
| | | | - Kieron Dunleavy
- MedStar Georgetown University Hospital, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC
| | - Abbey Fueger
- The Leukemia and Lymphoma Society, Rye Brook, NY
| | - Lee Jones
- Fight Colorectal Cancer, Arlington, VA
| | - Amar H Kelkar
- Harvard Medical School, Dana Farber Cancer Institute, Boston, MA
| | | | | | - Per Ljungman
- Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Eric D Miller
- The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Larissa A Meyer
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Heloisa P Soares
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT
| | | | | | - Elise C Kohn
- Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD
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3
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Hu J, Zhao J, Wang C, Jia M, Su M, Li S. Epstein-Barr virus reactivation correlates with worse outcomes for patients exposed to hepatitis B virus after haploidentical hematopoietic stem cell transplantation. Ann Hematol 2023; 102:3593-3601. [PMID: 37831153 DOI: 10.1007/s00277-023-05492-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/03/2023] [Indexed: 10/14/2023]
Abstract
Hepatitis B virus (HBV)has a high, chronic infection rate in Asian populations, but only few studies have analyzed the effect of Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) reactivation in patients exposed to HBV after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study aimed to assess the clinical outcomes of these patients. We conducted a retrospective research including 61 patients exposed to HBV after undergoing haplo-HSCT. The patients were classified into two groups: the CMV reactivation group and no CMV reactivation group. The results were compared between the two groups using the K-W test for continuous variables, Pearson's chi-square test for categorical variables, Kaplan-Meier curves to estimate overall survival (OS) and leukemia-free survival (LFS), and a Cox proportional hazards model to analyze multivariable influences. The 3-year cumulative HBV reactivation rate was 8.2%. The median duration of HBV reactivation was 16 months (16-22 months) after haplo-HSCT. The CMV reactivation group had a higher cumulative incidence of HBV reactivation than the group without CMV reactivation. The EBV reactivation was substantially higher in the CMV reactivation group compared to that in the no CMV reactivation group (37.0% vs.5.9% respectively; P = 0.002). Furthermore, EBV reactivation was a risk factor for 1-year LFS and 1-year OS. Based on our data, EBV reactivation was related to worse outcomes in patients exposed to HBV after haplo-HSCT, whereas CMV reactivation was not.
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Affiliation(s)
- Jiajia Hu
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China
| | - Jie Zhao
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China
| | - Chunyan Wang
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China
| | - Mei Jia
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China
| | - Ming Su
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
| | - Shanshan Li
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
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4
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Viscovo M, Metafuni E, Giammarco S, Santopaolo F, Frioni F, Pellegrino C, Sica S, Chiusolo P, Pompili M. Late HBV reactivation after hematopoietic stem cell transplantation, despite long-term prophylaxis. Eur J Clin Microbiol Infect Dis 2023; 42:1543-1545. [PMID: 37870712 DOI: 10.1007/s10096-023-04685-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 10/13/2023] [Indexed: 10/24/2023]
Affiliation(s)
- Marcello Viscovo
- Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Facoltà Di Medicina E Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Elisabetta Metafuni
- Dipartimento Di Diagnostica Per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica Ed Ematologia, Rome, Italy
| | - Sabrina Giammarco
- Dipartimento Di Diagnostica Per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica Ed Ematologia, Rome, Italy
| | - Francesco Santopaolo
- Dipartimento Di Scienze Mediche E Chirurgiche, Facoltà Di Medicina E Chirurgia, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, "Agostino Gemelli", Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Filippo Frioni
- Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Facoltà Di Medicina E Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Claudio Pellegrino
- Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Facoltà Di Medicina E Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Simona Sica
- Dipartimento Di Diagnostica Per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica Ed Ematologia, Rome, Italy
- Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Patrizia Chiusolo
- Dipartimento Di Diagnostica Per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica Ed Ematologia, Rome, Italy.
- Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Maurizio Pompili
- Dipartimento Di Scienze Mediche E Chirurgiche, Facoltà Di Medicina E Chirurgia, Fondazione Policlinico Gemelli, Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, "Agostino Gemelli", Largo A. Gemelli, 8, 00168, Rome, Italy
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5
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Ren J, Lin Q, Chen Q, Xu J, Chen D, Chen R, Lin K, Zhu H, Ye C, Luo X, Chen S, Kong H, Lin Q, Li N, Lin X, Chen Z, Hu J, Yang T. Adoptive immune transfer from donors offers Anti-HBV protection to HBsAb-negative patients after Allo-HSCT. iScience 2023; 26:106290. [PMID: 36936790 PMCID: PMC10014299 DOI: 10.1016/j.isci.2023.106290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 01/07/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023] Open
Abstract
Adoptive transfer of hepatitis B virus (HBV) immunity may occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we investigated the adoptive transfer of HBV immunity in 112 patients without HBV surface antibody (HBsAb) (HBsAb-) at the time of their first allo-HSCT. After allo-HSCT, HBV-DNA（87.5%） and HBsAg（11.1%%）cleared in HBsAg+ patients. All HBsAg- patients acquired HBsAb immediately. Nevertheless, HBsAb titers subsequently declined, and 39/67 (58.2%) patients lost HBsAb during follow-up. The 5-year overall survival (OS) was better in patients who lost HBsAb. Multivariate analysis showed that the independent risk factors for OS were lack of cytomegalovirus (CMV) clearance, acute graft-versus-host disease (aGVHD), and no HBsAb loss. Overall, adoptive immune transfer offers anti-HBV protection to patients without HBsAb, as they acquire HBsAb and clear HBV-DNA and HBsAg, while HBsAb loss after allo-HSCT predicts better survival.
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Affiliation(s)
- Jinhua Ren
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - QiaoXian Lin
- Department of Hematology, The First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, 350005, Fuzhou, Fujian, P. R. China
| | - Qi Chen
- Department of Hematology, Ningde municipal hospital of Ningde normal university, 13 Mindong Dong Road, 352100, Ningde, Fujian, P. R. China
| | - Jingjing Xu
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Dabin Chen
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Renli Chen
- Department of Hematology, Ningde municipal hospital of Ningde normal university, 13 Mindong Dong Road, 352100, Ningde, Fujian, P. R. China
| | - Kangni Lin
- Department of Critical Care Medicine, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian, P. R. China
| | - Haojie Zhu
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Chenjing Ye
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Xiaofeng Luo
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Shaozhen Chen
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Hui Kong
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Qiong Lin
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Nan Li
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Xu Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350122, China
| | - Zhizhe Chen
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
| | - Jianda Hu
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
- Corresponding author
| | - Ting Yang
- Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, 29 Xinquan Road, 350001, Fuzhou, Fujian, P. R. China
- Corresponding author
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6
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Sun X, Fu H, Wang C, Zhang Y, Han W, Chen H, Wang Y, Chen Q, He Y, Huang Q, Yan C, Chen Y, Han T, Lv M, Mo X, Wang J, Wang F, Chen Y, Zhu X, Xu L, Liu K, Huang X, Zhang X. Predicting the loss of hepatitis B surface antigen following haematopoietic stem cell transplantation in patients with chronic HBV infection. Bone Marrow Transplant 2023; 58:265-272. [PMID: 36456810 DOI: 10.1038/s41409-022-01880-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 11/12/2022] [Accepted: 11/17/2022] [Indexed: 12/05/2022]
Abstract
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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Affiliation(s)
- Xueyan Sun
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Haixia Fu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Chencong Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Yuanyuan Zhang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Wei Han
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Huan Chen
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Qi Chen
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Yun He
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Qiusha Huang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Chenhua Yan
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Yao Chen
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Tingting Han
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Meng Lv
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Xiaodong Mo
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Jingzhi Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Fengrong Wang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Yuhong Chen
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Xiaolu Zhu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Lanping Xu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Kaiyan Liu
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Xiaojun Huang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.,Collaborative Innovation Center of Haematology, Peking University, Beijing, China.,National Clinical Research Center for Haematologic Disease, Beijing, China
| | - Xiaohui Zhang
- Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China. .,Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China. .,Collaborative Innovation Center of Haematology, Peking University, Beijing, China. .,National Clinical Research Center for Haematologic Disease, Beijing, China.
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7
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Papatheodoridis GV, Lekakis V, Voulgaris T, Lampertico P, Berg T, Chan HLY, Kao JH, Terrault N, Lok AS, Reddy KR. Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion. J Hepatol 2022; 77:1670-1689. [PMID: 35850281 DOI: 10.1016/j.jhep.2022.07.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 07/01/2022] [Accepted: 07/06/2022] [Indexed: 12/27/2022]
Abstract
HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorised the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%). Our search uncovered 59 studies, including 3,424 HBsAg+ and 5,799 HBsAg-/anti-HBc+ patients, which met our eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumour necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs - either approach may be appropriate for intermediate-risk drugs. Consensus on definitions and methods of reporting HBVr, along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies.
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Affiliation(s)
- George V Papatheodoridis
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Vasileios Lekakis
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Thodoris Voulgaris
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Pietro Lampertico
- Fondazione 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
| | - Thomas Berg
- Division of Hepatology, Department of Medicine, Leipzig University Hospital, Leipzig, Germany
| | - Henry L Y Chan
- Division of Gastroenterology and Hepatology, Union Hospital and Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Norah Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
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8
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Xu XB, Hu C, Yang HJ, Zheng SS. Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection. Hepatobiliary Pancreat Dis Int 2022; 21:472-478. [PMID: 35948505 DOI: 10.1016/j.hbpd.2022.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a poorly understood and aggressive malignancy with increasing incidence and mortality. Hepatitis B virus (HBV) infection is recognized as one of the important risk factors of ICC. There are few reports focusing on whether isolated antibody to hepatitis B core antigen (isolated anti-HBc, IAHBc) have prognostic role in ICC, while positive hepatitis B surface antigen (HBsAg) has been reported to be associated with the prognosis of ICC. The aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection, in order to identify those who have the high risk of ICC recurrence in the early stage. METHODS We divided 209 ICC patients who underwent curative resection into 4 groups: group I (n = 40), HBsAg (-)/antibody to hepatitis B surface antigen (anti-HBs) (-)/anti-HBc (+); group II (n = 70), HBsAg (+)/anti-HBc (-); group III (n = 55), HBsAg (-)/anti-HBs (+)/anti-HBc (+); and group IV (n = 44), HBsAg (-)/anti-HBc (-). We compared the recurrence-free survival (RFS) and overall survival (OS) among these four groups. RESULTS The median follow-up time was 16.93 months (range 1-34.6 months). The 1- and 2-year RFS and OS rates were 60% and 42%, and 78% and 63% respectively in all patients. Compared to the whole non-IAHBc patients (group II + group III + group IV), IAHBc patients (group I) showed significantly lower RFS at 1 year (39.8% vs. 64.4%, P = 0.001) and 2 years (20.7% vs. 46.7%, P = 0.001). When compared to other three individual groups, IAHBc patients (group I) also had the lowest RFS. We did not find significant difference in OS among the four groups. Further multivariate analysis revealed that IAHBc was an independent risk factor of RFS. CONCLUSIONS IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.
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Affiliation(s)
- Xiao-Bo Xu
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou 310012, China
| | - Chen Hu
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Han-Jin Yang
- Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
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9
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Kantar FU, Kahraman S, Ece G, Cagırgan S. Hepatitis B sero-prevalence among hematology patients: importance of Anti-HbcAb and efficiency of antiviral prophylaxis. Afr Health Sci 2022; 22:561-566. [PMID: 36910386 PMCID: PMC9993312 DOI: 10.4314/ahs.v22i3.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objectives Hepatitis B infection is an important problem in immune suppressed patients. Anti HbcAb is an important marker that shows past exposure to virus. In this study, we retrospectively searched HBV serology among the patients who had Bone Marrow Transplantation (BMT) or chemotherapies (CT) at Medicalpark Izmir Hospital Bone Marrow Transplantation Unit; changes in viral parameters throughout therapy; and tried to find the efficiency of antiviral prophylaxis. Methods We retrospectively evaluated the viral parameters; HbsAg, Anti HbsAb, Anti Hbc IgG, HbeAg, Anti Hbe Ab, HBV DNA, HCV RNA which were carried out before BMT and CT. We grouped the patients as latent HBV infection and inactive carriers. Started antiviral treatment as prophylaxis, monitored the changes in serological parameters and defined HBV related situations. Results A total of 584 patients were evaluated retrospectively. Twenty patients were having latent HBV infection. Ten patients were inactive carriers of HBV. In post-transplant period, the patients were screened for 11 months (1-38 months). None of the patients experienced HBV activation during follow period. Conclusion The best approach in HbcAb positive patients with planned immunosuppressive treatment is the use of anti-viral agents before immune suppression and close monitoring of the patients HBV-related markers.
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Affiliation(s)
| | - Selda Kahraman
- Medicalpark Izmir Hospital, Department of Hematology, Izmir, Turkey
| | - Gulfem Ece
- Izmir University of Economics, School of Medicine, Medicalpark Izmir Hospital, Department of Medical Microbiology, Izmir, Turkey
| | - Seckin Cagırgan
- Medical park Izmir Hospital, Department of Hematology, Izmir, Turkey
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10
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Hammond SP, Ho VT, Marty FM. Hepatitis B virus vaccination after allogeneic hematopoietic cell transplantation prevents post-transplant HBV reactivation. Transplant Cell Ther 2022; 28:402.e1-402.e5. [PMID: 35413458 DOI: 10.1016/j.jtct.2022.04.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/04/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) reactivation in allogeneic hematopoietic-cell transplant (HCT) recipients with evidence of pre-transplantation resolved HBV infection is an important cause of morbidity, usually occurring a year or later after HCT. OBJECTIVES We retrospectively studied a cohort of allogeneic HCT recipients with resolved HBV infection, some of whom were vaccinated for HBV following transplantation, to understand if post-HCT HBV vaccination influenced the risk of HBV reactivation. STUDY DESIGN The study included all patients with resolved HBV who underwent allogeneic HCT at our institution between 1/1/2000 and 12/31/2015, where HBV vaccination starting at 1 year after HCT became standard in 2012 and antiviral prophylaxis is not utilized. Resolved HBV infection was defined as positive HBV-core IgG (HBcAb), negative HBV-surface antigen (HBsAg) and undetectable HBV DNA before HCT. HBV reactivation was defined as development of detectable HBsAg and HBV DNA after HCT. Follow up for outcomes concluded 1/1/2018. RESULTS Among 136 patients with resolved HBV before HCT, 19 developed reactivation during follow up (cumulative incidence 14%). Median time to HBV reactivation was 21 months (range, 2-47 months). The cumulative probability of HBV reactivation among HCT recipients who survived for a year or more after transplant without early HBV reactivation and were HBV-vaccinated versus those who were unvaccinated was 2.9% vs. 10.0 % at two years and 6.6% vs. 26.5% at 4 years post-HCT (P = 0.03, Gray's test). In a time-dependent Cox model, the adjusted hazard ratio (aHR) of HBV reactivation in patients with pre-transplant HBsAb levels greater than 10 IU/L was 0.34 (95% confidence interval [CI], 0.13-0.90). The aHR of HBV reactivation in patients who were vaccinated with 2 or more doses of recombinant HBV vaccine after HCT was 0.18 (95% CI, 0.04-0.80) compared to those who received 1 or no post-HCT vaccine doses. CONCLUSIONS HBV reactivation is a late complication of allogeneic HCT in at-risk recipients, particularly in those with low pre-HCT HBsAb. HBV vaccination starting 1 year after HCT may be protective.
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Affiliation(s)
- Sarah P Hammond
- Division of Infectious Diseases, Boston, MA 02115; Dana-Farber Cancer Institute, Boston, MA 02115; Harvard Medical School, Boston, MA 02115; Divisions of Infectious Diseases and Hematology/Oncology, Massachusetts General Hospital, Boston, MA 02114.
| | - Vincent T Ho
- Division of Medical Oncology, Boston, MA 02115; Dana-Farber Cancer Institute, Boston, MA 02115; Harvard Medical School, Boston, MA 02115
| | - Francisco M Marty
- Division of Infectious Diseases, Boston, MA 02115; Dana-Farber Cancer Institute, Boston, MA 02115; Harvard Medical School, Boston, MA 02115
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11
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Gama JFG, Cardoso LMDF, Lagrota-Candido JM, Alves LA. Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition? World J Clin Cases 2022; 10:2685-2697. [DOI: 10.12998/wjcc.v10.i9.2685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.
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Affiliation(s)
- Jaciara Fernanda Gomes Gama
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Liana Monteiro da Fonseca Cardoso
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Jussara Machado Lagrota-Candido
- Laboratory of Immunopathology, Department of Immunobiology, Fluminense Federal University, Niteroi 24210-200, Rio de Janeiro, Brazil
| | - Luiz Anastacio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
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12
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Gama JFG, Cardoso LMDF, Lagrota-Candido JM, Alves LA. Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition? World J Clin Cases 2022; 10:2687-2699. [PMID: 35434112 PMCID: PMC8968822 DOI: 10.12998/wjcc.v10.i9.2687] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/20/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.
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Affiliation(s)
- Jaciara Fernanda Gomes Gama
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Liana Monteiro da Fonseca Cardoso
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Jussara Machado Lagrota-Candido
- Laboratory of Immunopathology, Department of Immunobiology, Fluminense Federal University, Niteroi 24210-200, Rio de Janeiro, Brazil
| | - Luiz Anastacio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
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13
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Abstract
Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.
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Affiliation(s)
- Wei Huang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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14
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Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. J Pers Med 2021; 11:jpm11111108. [PMID: 34834460 PMCID: PMC8619006 DOI: 10.3390/jpm11111108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 01/12/2023] Open
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.
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15
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Yu C, Sun Y, Xu L, Zhang X, Liu K, Jin J, Huang X, Wang Y. Hepatitis B Seropositive Status in Recipients or Donors Is Not Related to Worse Outcomes after Haploidentical Hematopoietic Stem Cell Transplantation. Transplant Cell Ther 2021; 27:668.e1-668.e9. [PMID: 34052506 DOI: 10.1016/j.jtct.2021.05.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/15/2021] [Accepted: 05/19/2021] [Indexed: 12/19/2022]
Abstract
Hepatitis B virus (HBV) has a high rate of chronic infection in Asian populations, and only limited studies have been performed to analyze the impact of HBV-seropositive haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients and donors. The present study aimed to evaluate the effect on clinical outcomes in those patients. We conducted a retrospective study enrolling 237 consecutive patients undergoing first haplo-HSCT. The patients were classified into 3 groups: recipient HBV-positive group (R+D-; n = 62), donor HBV-positive group (D+; n = 83), and HBV-negative group (R-D-; n = 92). Corresponding prophylactic antiviral treatment was given in the R+D- and D+ groups. The results were compared among the 3 groups using the Kruskal-Wallis test for continuous variables, Pearson's chi-square test for categorical variables, the competing-risk method to evaluate cumulative incidence, Kaplan-Meier curves to estimate overall survival (OS) and disease-free survival (DFS), and a Cox proportional hazard model to analyze multivariable influences. The 3-year cumulative HBV reactivation rate was 4.2%. The median time to HBV reactivation was 845 days (range, 545 to 1439 days) after haplo-HSCT. The R+D- group tended to have a higher cumulative incidence of HBV reactivation compared with the D+ group (11.8% versus 3.1%; P = .080). Significant differences in the causes of hepatic damage were observed among the 3 groups (P = .017), and all patients with acute hepatitis B after haplo-HSCT were from the R+D- group. Multivariate analysis showed that pretransplantation HBV status was associated with cytomegalovirus reactivation (R+D- versus R-D-: hazard ratio, 1.514; 95% confidence interval, 1.060 to 2.163; P = .023). The 3-year OS and DFS, 3-year cumulative incidence of nonrelapse mortality (NRM), rates of relapse and graft-versus-host disease (GVHD), and causes of death were comparable among the 3 groups. Pretransplantation HBV serostatus had no significant effect on OS, DFS, NRM, relapse, or GVHD in the multivariate analysis. Based on our data, seropositivity for hepatitis B surface antigen (HbsAg) or core antibody (HBcAb) in donors or recipients before transplantation did not negatively affect the overall outcome after haplo-HSCT under the premise of proper antiviral prophylaxis along with regular post-transplantation surveillance, and HBV seropositivity should not be considered a contraindication to haplo-HSCT.
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Affiliation(s)
- Chunzi Yu
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Yuqian Sun
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Lanping Xu
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiaohui Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Kaiyan Liu
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Jian Jin
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Xiaojun Huang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
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16
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Niu JX, Xu Y, Wu DP. [Progress in the research of HBV reactivation in patients undergoing hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2021; 42:348-352. [PMID: 33979984 PMCID: PMC8120123 DOI: 10.3760/cma.j.issn.0253-2727.2021.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Indexed: 12/04/2022]
Affiliation(s)
- J X Niu
- Department of Hematology, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China
| | - Y Xu
- Department of Hematology, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China
| | - D P Wu
- Department of Hematology, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China
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17
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Wu Y, Huang H, Luo Y. Management of Hepatitis B Virus in Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol 2021; 11:610500. [PMID: 33613534 PMCID: PMC7890023 DOI: 10.3389/fimmu.2020.610500] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 12/22/2020] [Indexed: 12/16/2022] Open
Abstract
The high morbidity of HBV reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is partially due to the intense immunologic potency of complex therapeutic regimens, the use of antithymocyte globulin and calcineurin inhibitors to prevent graft versus-host disease (GVHD), prolonged immune reconstitution, and hematological malignancies infected with hepatitis B virus (HBV). Immunosuppression results in the reactivation of HBV replication from covalently closed circular DNA (cccDNA) residing in hepatocytes. However, the role of viral mutations during HBV reactivation needs to be validated. All individuals scheduled to receive allo-HSCT or wish to donate stem cells should be screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core (anti-HBc), and HBV-DNA. HBsAg-positive recipients of allo-HSCT have a high risk of HBV reactivation; thus, they should receive prophylactic antiviral therapy. The high barrier to resistance nucleos(t)-ide analogs (NAs) seems to be superior to the low barrier agents. Resolved-HBV recipients have a lower risk of HBV reactivation than HBsAg-positive recipients. Although prophylactic antiviral therapy remains controversial, regular monitoring of alanine transaminase (ALT) and HBV-DNA combined with preemptive antiviral treatment may be an optimized strategy. However, optimal antiviral therapy duration and time intervals for monitoring remain to be established. Accepting stem cells from HBsAg-positive donors is associated with a risk of developing HBV-related hepatitis. The overall intervention strategy, including donors and recipients, may decrease the risk of HBV-related hepatitis following HSCT from HBsAg positive stem cells. In this review, we summarize the issues of HBV in allo-HSCT, including HBV reactivation mechanism, HBsAg-positive recipients, HBV-resolved infection recipients, and donor-related factors, and discuss their significance.
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Affiliation(s)
- Yibo Wu
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
| | - He Huang
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
| | - Yi Luo
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
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18
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Overt gastrointestinal bleeding following haploidentical haematopoietic stem cell transplantation: incidence, outcomes and predictive models. Bone Marrow Transplant 2021; 56:1341-1351. [PMID: 33414512 DOI: 10.1038/s41409-020-01187-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 11/18/2020] [Accepted: 12/02/2020] [Indexed: 01/04/2023]
Abstract
Gastrointestinal bleeding (GIB) accounts for a significant proportion of life-threatening bleeding cases occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, data on GIB after haploidentical HSCT (haplo-HSCT) are not available. A total of 3180 patients received haplo-HSCT at Peking University People's Hospital from January 2015 to November 2019, and GIB occurred in 188 of these patients (incidence of 5.9%). Platelet counts <30 × 109/L, viral hepatitis, acute kidney injury (AKI), gastrointestinal disease or bleeding before HSCT and sinusoidal obstruction syndrome (SOS) were determined to be significant risk factors for the occurrence of GIB after haplo-HSCT. Grade III-IV acute graft-versus-host disease (aGVHD), AKI, thrombotic microangiopathy (TMA), disseminated intravascular coagulation (DIC) and gastrointestinal disease or bleeding before HSCT were significantly related to mortality in patients with GIB after haplo-HSCT. The predictive models developed for the occurrence and mortality of GIB performed well in terms of discrimination, and they might assist clinicians with personalised strategies for GIB prevention and treatment in patients after haplo-HSCT.
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Piekarska A, Wisniewski P, Lewandowski K, Gil L, Trzonkowski P, Bieniaszewska M, Zaucha JM. Immune Status Against Hepatitis B in Patients After Allogeneic Hematopoietic Cell Transplantation-Factors Affecting Early and Long-Lasting Maintenance of Protective Anti-HBs Titers. Front Immunol 2020; 11:586523. [PMID: 33335530 PMCID: PMC7736697 DOI: 10.3389/fimmu.2020.586523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 10/28/2020] [Indexed: 11/13/2022] Open
Abstract
The immunization of allogeneic hematopoietic cell transplantation (HCT) recipients against vaccine-preventable diseases is a part of posttransplantation guidelines. We conducted a prospective study to assess clinical and immunological parameters that would determine the response and long-term maintenance of protective antibody titers upon the hepatitis B virus (HBV) vaccination after HCT. The investigated variables included: vaccination of the HCT recipients and their donors prior to HCT, chronic graft versus host disease (cGVHD) and the timing of post-HCT vaccination, and B- and T-cell subtype status. Forty-two patients were immunized with three or more doses of recombinant hepatitis B surface antigen (rHBsAg) administered according to the individualized schedule of 0-1-2-6-(12) months. After vaccination, seroconversion was achieved in the whole group. The vaccines were categorized according to the antibody (Ab) titers as weak (WRs; 28.7%), good (GRs; 38%) or very good responders (VGRs; 3.3%). In multivariate logistic regression, severe cGVHD (OR= 15.5), and preceding donor immunization (OR= 0.13) were independent predictors of a weak response to vaccination. A prior belonging to the WR group impaired the durability of protection (OR= 0.17) at a median follow-up of 11.5 years. Patients with severe cGVHD showed a trend toward lower median Ab titers, although they required a higher rate of booster vaccine doses. All VGRs had CD4+ cells > 0.2 x 106/L. There was a lower mean rate of CD4+IL2+ lymphocytes in WRs. Vaccination demonstrated the immunomodulatory effect on B-cell and T-cell subsets and a Th1/Th2 cytokine profile, while shifts depended on a history of severe cGVHD and the type of vaccine responder. To conclude, vaccination of HCT donors against HBV allows a better response to vaccination in the respective HCT recipients. Double doses of rHBsAg should be considered in patients with cGVHD and in those not immunized before HCT. A dedicated intensified vaccination schedule should be administered to WRs.
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Affiliation(s)
- Agnieszka Piekarska
- Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland
| | - Piotr Wisniewski
- Department of Endocrinology and Internal Diseases, Medical University of Gdansk, Gdansk, Poland
| | | | - Lidia Gil
- Department of Hematology and Stem Cell Transplantation, Poznan University of Medical Sciences, Poznan, Poland
| | - Piotr Trzonkowski
- Department of Clinical Immunology, Medical University of Gdansk, Gdansk, Poland
| | - Maria Bieniaszewska
- Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland
| | - Jan Maciej Zaucha
- Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland
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20
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Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
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Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
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21
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Wu T, Wu N, Ma YX, Wu J, Gao Y, Pan XB. Role of hepatitis B antibody in predicting reactivation of resolved hepatitis B virus infection in leukemia patients. Antiviral Res 2020; 177:104765. [PMID: 32171856 DOI: 10.1016/j.antiviral.2020.104765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/02/2020] [Accepted: 03/07/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Quantification of anti-HBs and anti-HBc predicts the risk of HBV reactivation (HBVr) in lymphoma patients receiving rituximab treatment. However, it remains unclear whether the quantification is predictive of HBVr in leukemia patients undergoing immunosuppression. METHODS and patients: Clinical and laboratory data of the leukemia patients with resolved HBV infection diagnosed between January 2013 and March 2018 were retrospectively collected. Data series of HBV seromarkers and HBV DNA levels before the patients receiving chemotherapy and/or hematopoietic stem cell transplantation (HSCT) and during follow-up duration were analyzed. RESULTS In total, 533 leukemia patients with resolved HBV infection were included. The incidences of HBVr were 5.7% (25/441) and 2.2% (2/92) in patients receiving HSCT and chemotherapy, respectively. In patients receiving HSCT, acute lymphoid leukemia had a significantly higher incidence of HBVr than acute myeloid leukemia (8.9% vs 3.9%, P < 0.05). The incidence varied almost zero to 40% due to the differences in the profiles of HBV antibodies. High anti-HBs (cut-off of 79.2 IU/L) or low anti-HBc levels (cut-off of 4.475, S/CO) at baseline were associated with a low risk of HBVr. Anti-HBe status did not affect the incidence of HBVr. However, the cut-offs were only predictive of HBVr in the patients who had negative anti-HBe. CONCLUSION The baseline profiles of HBV antibodies are predictive of the risk of HBVr in leukemia patients undergoing immunosuppression. However, seronegative anti-HBe is a prerequisite for using baseline anti-HBs and anti-HBc quantification to predict HBVr risk.
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Affiliation(s)
- Tian Wu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Nan Wu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Yan-Xiu Ma
- Hangzhou Normal University, School of Medicine, Department of Basic Medical Science, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Key Laboratory of Inflammation and Immunoregulation of Hangzhou, Hangzhou, Zhejiang, China
| | - Jing Wu
- Hangzhou Normal University, School of Medicine, Department of Basic Medical Science, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Key Laboratory of Inflammation and Immunoregulation of Hangzhou, Hangzhou, Zhejiang, China
| | - Yan Gao
- Peking University People's Hospital, Department of Infectious Disease, Beijing, China.
| | - Xiao-Ben Pan
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China; Hangzhou Normal University, School of Medicine, Department of Basic Medical Science, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Key Laboratory of Inflammation and Immunoregulation of Hangzhou, Hangzhou, Zhejiang, China.
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22
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Cheung CKM, Law MF, Chao DC, Wong SH, Ho R, Chao ACW, Lai JWY, Chan TYT, Tam MTK, Lau SLF, Tam THC. Prevention of hepatitis B virus reactivation in patients with hematological malignancies and resolved hepatitis B virus infection: a systematic review and meta-analysis. J Dig Dis 2020; 21:160-169. [PMID: 32040243 DOI: 10.1111/1751-2980.12848] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 01/25/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Patients with resolved hepatitis B virus (HBV) infection are at risk of HBV reactivation during treatment for hematological malignancies. We conducted a systematic review and meta-analysis of the data on the efficacy of antiviral prophylaxis for the prevention of HBV reactivation in this group of patients. METHODS We conducted a systemic literature search of PubMed including MEDLINE and EMBASE databases to 31 January 2019 to identify studies published in English comparing antiviral prophylaxis with no prophylaxis for HBV reactivation in patients treated for hematological malignancies. The search terms used were ("occult hepatitis B" OR "resolved hepatitis B") AND ("reactivation") AND ("haematological malignancy" OR "hematological malignancy" OR "chemotherapy" OR "immunotherapy" OR "chemoimmunotherapy" OR "lymphoma" OR "leukemia" OR "transplant"). The primary outcome was the reactivation of HBV infection. Pooled estimates of relative risk (RR) were calculated. RESULTS We identified 13 relevant studies including two randomized controlled trials (RCT), one post hoc analysis from RCT and 10 cohort studies. There was a trend towards a lower rate of HBV reactivation using antiviral prophylaxis, but the difference was not significant (RR 0.57, 95% confidence interval [CI] 0.23-1.40, P = 0.22). When limiting the analysis to the three prospective studies of patients receiving anti-CD20 monoclonal antibodies, we found antiviral prophylaxis was associated with a significantly lower risk of HBV reactivation (RR 0.17, 95% CI 0.06-0.49, P = 0.001). CONCLUSION Antiviral prophylaxis reduced the risk of HBV reactivation in patients receiving anti-CD20 monoclonal antibodies for hematological malignancies but not in a broader group of patients receiving anticancer therapy.
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Affiliation(s)
- Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - David Chun Chao
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Sunny Hei Wong
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong SAR, China
| | - Amelia Chien Wei Chao
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Jennifer Wing Yan Lai
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Ted Yun Tat Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Mark Tsz Kin Tam
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Sam Lik Fung Lau
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
| | - Tommy Ho Chi Tam
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
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Zhang A, Wu Y, Tan Y, Shi J, Zhao Y, Hu Y, Yu J, Zheng W, Lai X, Zhang M, Zhu Y, Ye Y, Huang Y, Fu S, Huang H, Luo Y. Determining Whether Prophylactic Antiviral Treatment Is Necessary in HBsAg-Negative/HBcAb-Positive Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2020; 26:956-964. [PMID: 31962163 DOI: 10.1016/j.bbmt.2020.01.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 12/25/2019] [Accepted: 01/07/2020] [Indexed: 12/18/2022]
Abstract
The incidence of hepatitis B virus (HBV) infection is high in the Asian population. Increasing attention is being given to the risk of HBV reactivation in hepatitis B core antibody-positive [HBcAb(+)] patients during immunosuppressive therapy. Knowledge of HBV reactivation in hematopoietic stem cell transplantation (HSCT) is limited. Moreover, the effect of hepatitis B surface antibody (HBsAb) on HBV reactivation in HBcAb(+) patients during HSCT remains uncertain. We sought to investigate the role of HBsAb and the need for prophylactic antiviral treatment in hepatitis B surface antigen-negative [HBsAg(-)]/HBcAb(+) patients during HSCT. We classified 665 HBsAg(-) HSCT recipients into 4 groups: HBcAb(-)HBsAb(-) (n = 189), HBcAb(-)HBsAb(+) (n = 176), HBcAb(+)HBsAb(-) (n = 49), and HBcAb(+)HBsAb(+) (n = 251). HBV reactivation was identified in 16 patients after HSCT. The median time to HBV reactivation was 645 days (range, 455 to 1957 days) after transplantation. The cumulative HBV reactivation rate was significantly higher in the HBcAb(+)HBsAb(-) group compared with the HBcAb(+)HBsAb(+), HBcAb(-)HBsAb(-), and HBcAb(-)HBsAb(+) groups, respectively (P< .001). Notably, the risk of HBV reactivation was significantly higher in the HBcAb(+)HBsAb(-) group compared with the HBcAb(+)HBsAb(+) group (P= .007; hazard ratio, 4.750; 95% confidence interval, 1.531 to 14.737). Our results point to a protective role of HBsAb in HBV-resolved patients undergoing HSCT and indicate that prophylactic anti-HBV treatment might not be mandatory for HBsAg(-), HBcAb(+)HBsAb(+) patients following HSCT. The surveillance protocol of intense follow-up early (HBV DNA and HBsAg monthly) might not be necessary.
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Affiliation(s)
- Aibin Zhang
- Division of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yibo Wu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jimin Shi
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yongxian Hu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Yu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weiyan Zheng
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoyu Lai
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mingming Zhang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuanyuan Zhu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yishan Ye
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yaping Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shan Fu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Luo
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Sano T, Akuta N, Suzuki Y, Kasuya K, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Saitoh S, Kobayashi M, Suzuki F, Kobayashi M, Arase Y, Ikeda K, Kumada H. Fulminant Hepatitis due to de novo Hepatitis B after Cord Blood Transplantation Rescued by Medical Treatment. Intern Med 2020; 59:1519-1524. [PMID: 32536678 PMCID: PMC7364250 DOI: 10.2169/internalmedicine.4190-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.
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Affiliation(s)
- Tomoya Sano
- Department of Hepatology, Toranomon Hospital, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Japan
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25
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Gentile G, Antonelli G. HBV Reactivation in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Narrative Review. Viruses 2019; 11:v11111049. [PMID: 31717647 PMCID: PMC6893755 DOI: 10.3390/v11111049] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 10/30/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
HBV reactivation (HBVr) can occur due to the ability of HBV to remain latent in the liver as covalently closed circular DNA and by the capacity of HBV to alter the immune system of the infected individuals. HBVr can occur in patients undergoing hematopoietic stem cell transplantation (HSCT) with a clinical spectrum that ranges from asymptomatic infection to fulminant hepatic failure. The risk of HBVr is determined by a complex interplay between host immunity, virus factors, and immunosuppression related to HSCT. All individuals who undergo HSCT should be screened for HBV. HSCT patients positive for HBsAg and also those HBcAb-positive/HBsAg-negative are at high risk of HBV reactivation (HBVr) due to profound and prolonged immunosuppression. Antiviral prophylaxis prevents HBVr, decreases HBVr-related morbidity and mortality in patients with chronic or previous HBV. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naïve recipients and their donors against HBV prior to HSCT has an important role in the prevention of acquired HBV infection. This narrative review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of HBVr in HSCT.
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Affiliation(s)
- Giuseppe Gentile
- Dept. Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
- Correspondence: or
| | - Guido Antonelli
- Dept. Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
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26
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Sasadeusz J, Grigg A, Hughes PD, Lee Lim S, Lucas M, McColl G, McLachlan SA, Peters MG, Shackel N, Slavin M, Sundararajan V, Thompson A, Doyle J, Rickard J, De Cruz P, Gish RG, Visvanathan K. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Transplant Recipients. Clin Liver Dis 2019; 23:493-509. [PMID: 31266623 DOI: 10.1016/j.cld.2019.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur; this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.
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Affiliation(s)
- Joe Sasadeusz
- Peter Doherty Institute for Infection and Immunity, Elizabeth Street, Melbourne, Victoria 3000, Australia; University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
| | - Andrew Grigg
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter D Hughes
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia
| | - Seng Lee Lim
- National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
| | - Michaela Lucas
- University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
| | - Geoff McColl
- University of Queensland Oral Health Centre, 288 Herston Road, Queensland 4006, Australia
| | - Sue Anne McLachlan
- St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Marion G Peters
- University of California, San Francisco, S357 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Nicholas Shackel
- Ingham Institute, 1 Campbell Street, Liverpool, Sydney, New South Wales 2170, Australia
| | - Monica Slavin
- Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia; Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
| | - Vijaya Sundararajan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia; Department of Public Health, La Trobe University, Plenty Road, Bundoora, Victoria 3086, Australia
| | - Alexander Thompson
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Joseph Doyle
- The Alfred and Monash University, 85 Commercial Road, Melbourne, Victoria 3004, Australia; Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia
| | - James Rickard
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter De Cruz
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia
| | - Robert G Gish
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
| | - Kumar Visvanathan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
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Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, Saigal S, Saraf N, Soin AS, Devarbhavi H, Kim DJ, Dhiman RK, Duseja A, Taneja S, Eapen CE, Goel A, Ning Q, Chen T, Ma K, Duan Z, Yu C, Treeprasertsuk S, Hamid SS, Butt AS, Jafri W, Shukla A, Saraswat V, Tan SS, Sood A, Midha V, Goyal O, Ghazinyan H, Arora A, Hu J, Sahu M, Rao PN, Lee GH, Lim SG, Lesmana LA, Lesmana CR, Shah S, Prasad VGM, Payawal DA, Abbas Z, Dokmeci AK, Sollano JD, Carpio G, Shresta A, Lau GK, Fazal Karim M, Shiha G, Gani R, Kalista KF, Yuen MF, Alam S, Khanna R, Sood V, Lal BB, Pamecha V, Jindal A, Rajan V, Arora V, Yokosuka O, Niriella MA, Li H, Qi X, Tanaka A, Mochida S, Chaudhuri DR, Gane E, Win KM, Chen WT, Rela M, Kapoor D, Rastogi A, Kale P, Rastogi A, Sharma CB, Bajpai M, Singh V, Premkumar M, Maharashi S, Olithselvan A, Philips CA, Srivastava A, Yachha SK, Wani ZA, Thapa BR, Saraya A, Shalimar, Kumar A, Wadhawan M, Gupta S, Madan K, Sakhuja P, Vij V, Sharma BC, Garg H, Garg V, Kalal C, et alSarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, Saigal S, Saraf N, Soin AS, Devarbhavi H, Kim DJ, Dhiman RK, Duseja A, Taneja S, Eapen CE, Goel A, Ning Q, Chen T, Ma K, Duan Z, Yu C, Treeprasertsuk S, Hamid SS, Butt AS, Jafri W, Shukla A, Saraswat V, Tan SS, Sood A, Midha V, Goyal O, Ghazinyan H, Arora A, Hu J, Sahu M, Rao PN, Lee GH, Lim SG, Lesmana LA, Lesmana CR, Shah S, Prasad VGM, Payawal DA, Abbas Z, Dokmeci AK, Sollano JD, Carpio G, Shresta A, Lau GK, Fazal Karim M, Shiha G, Gani R, Kalista KF, Yuen MF, Alam S, Khanna R, Sood V, Lal BB, Pamecha V, Jindal A, Rajan V, Arora V, Yokosuka O, Niriella MA, Li H, Qi X, Tanaka A, Mochida S, Chaudhuri DR, Gane E, Win KM, Chen WT, Rela M, Kapoor D, Rastogi A, Kale P, Rastogi A, Sharma CB, Bajpai M, Singh V, Premkumar M, Maharashi S, Olithselvan A, Philips CA, Srivastava A, Yachha SK, Wani ZA, Thapa BR, Saraya A, Shalimar, Kumar A, Wadhawan M, Gupta S, Madan K, Sakhuja P, Vij V, Sharma BC, Garg H, Garg V, Kalal C, Anand L, Vyas T, Mathur RP, Kumar G, Jain P, Pasupuleti SSR, Chawla YK, Chowdhury A, Alam S, Song DS, Yang JM, Yoon EL. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019; 13:353-390. [PMID: 31172417 PMCID: PMC6728300 DOI: 10.1007/s12072-019-09946-3] [Show More Authors] [Citation(s) in RCA: 562] [Impact Index Per Article: 93.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023]
Abstract
The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj K Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sanjiv Saigal
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - A S Soin
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | | | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea
| | - R K Dhiman
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, PGIMER, Chandigarh, India
| | - C E Eapen
- Department of Hepatology, CMC, Vellore, India
| | - Ashish Goel
- Department of Hepatology, CMC, Vellore, India
| | - Q Ning
- Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Chen
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Ke Ma
- Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Z Duan
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Chen Yu
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | | | - S S Hamid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Amna S Butt
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Akash Shukla
- Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | | | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
| | - Ajit Sood
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Vandana Midha
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Omesh Goyal
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital and GRIPMER, New Delhi, Delhi, India
| | - Jinhua Hu
- Department of Medicine, 302 Millitary Hospital, Beijing, China
| | - Manoj Sahu
- Department of Gastroenterology and Hepatology Sciences, IMS & SUM Hospital, Bhubaneswar, Odisha, India
| | - P N Rao
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Guan H Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Seng G Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | | | | | - Samir Shah
- Department of Hepatology, Global Hospitals, Mumbai, India
| | | | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Zaigham Abbas
- Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
| | - A Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Jose D Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Gian Carpio
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Ananta Shresta
- Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal
| | - G K Lau
- Department of Medicine, Humanity and Health Medical Group, New Kowloon, Hong Kong, China
| | - Md Fazal Karim
- Department of Hepatology, Sir Salimullah Medical College, Dhaka, Bangladesh
| | - Gamal Shiha
- Egyptian Liver Research Institute And Hospital, Cairo, Egypt
| | - Rino Gani
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Kemal Fariz Kalista
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital Hong Kong, The University of Hong Kong, Hong Kong, China
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Viniyendra Pamecha
- Department of Hepatobilliary Pancreatic Surgery and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - V Rajan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaolong Qi
- CHESS Frontier Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Atsushi Tanaka
- Department of Medicine, Tokyo University School of Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | | | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland Hospital, Auckland, New Zealand
| | | | - Wei Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Mohd Rela
- Department of Liver Transplant Surgery, Dr. Rela Institute and Medical Centre, Chennai, India
| | | | - Amit Rastogi
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - Pratibha Kale
- Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Chhagan Bihari Sharma
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Meenu Bajpai
- Department of Immunohematology and Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | | | | | | | - A Olithselvan
- Division of Liver Transplantation and Hepatology, Manipal Hospitals, Bangalore, India
| | - Cyriac Abby Philips
- The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, SGPGIMS, Lucknow, India
| | | | | | - B R Thapa
- Department of Gastroenterology and Pediatric Gastroenterology, PGIMER, Chandigarh, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital and GRIPMER, New Delhi, Delhi, India
| | - Manav Wadhawan
- Department of Gastroenterology, Hepatology and Liver Transplant, B L K Hospital, New Delhi, India
| | - Subash Gupta
- Centre for Liver and Biliary Science, Max Hospital, New Delhi, India
| | - Kaushal Madan
- Department of Gastroenterology, Hepatology and Liver Transplant, Max Hospital, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GB Pant Hospital, New Delhi, India
| | - Vivek Vij
- Department of Liver Transplant and Hepatobilliary Surgery, Fortis Hospital, New Delhi, India
| | - Barjesh C Sharma
- Department of Gastroenterology, GB Pant Hospital, New Delhi, India
| | - Hitendra Garg
- Department of Gastroenterology, Hepatology and Liver Transplant, Apollo Hospital, New Delhi, India
| | - Vishal Garg
- Department of Gastroenterology, Hepatology and Liver Transplant, Apollo Hospital, New Delhi, India
| | - Chetan Kalal
- Department of Hepatology, Sir H N Reliance Hospital and Research Centre, Mumbai, India
| | - Lovkesh Anand
- Department of Gastroenterology and Hepatology, Narayana Hospital, Gurugram, India
| | - Tanmay Vyas
- Department of Hepatology, Parimal Multi-Speciality Hospital, Ahmedabad, India
| | - Rajan P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samba Siva Rao Pasupuleti
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Yogesh K Chawla
- Department of Hepatology and Gastroenterology, Kalinga Institute of Med Sciences, KIIT University, Bhubaneswar, India
| | - Abhijit Chowdhury
- Department of Hepatology, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Shahinul Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Do Seon Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Eileen L Yoon
- Department Of Internal Medicine, Inje University College of Medicine, Busan, South Korea
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28
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Liu JH, Liao XW, Chen CH, Yao M, Li CC, Lin CT, Tsai CH, Chou WC, Hou HA, Huang SY, Wu SJ, Chen YC, Tien HF, Tang JL, Ko BS. 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 2019; 186:72-85. [PMID: 30919947 DOI: 10.1111/bjh.15884] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 12/11/2018] [Indexed: 12/30/2022]
Abstract
Reactivation of hepatitis B virus (HBV) by reverse seroconversion (HBV-RS) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) can occur in patients with resolved HBV infection (rHBV, defined as negative HBV surface antigen [HBsAg] and positive HBV core antibody), and may cause fatal hepatitis. To explore the risk factors, we retrospectively identified 817 consecutive patients who underwent allo-HSCT from 2005 to 2016 in this largest single centre cohort from National Taiwan Univerisity Hospital. Transplants using donors or recipients positive for HBsAg or HBV DNA were excluded, leaving 445 rHBV patients for analysis. The 3- and 5-year cumulative incidence of HBV-RS after allo-HSCT was 8·7% and 10·5%, respectively, at a median 16 months after allo-HSCT. All had concurrent HBV reactivation. HBV flares developed in 19% of HBV-RS cases, but none experienced hepatic failure. Neither did it impact non-relapse mortality or overall survival. Multivariate analysis revealed that patients with donor lacking hepatitis B surface antibody and extensive chronic graft-versus-host disease (cGVHD) have the highest risk for HBV-RS, with 5-year incidence of 24·2%. In conclusion, adoptive immunity transfer from the donor seems to have protective effects against HBV-RS, which may alter future donor selection algorithms, and combined with extensive cGVHD provides a good target for risk-adaptive HBV prophylaxis.
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Affiliation(s)
- Jia-Hau Liu
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan.,Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Xiu-Wen Liao
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan
| | - Chien-Hung Chen
- Division of Gastrohepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming Yao
- Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Cheng Li
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan.,Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Division of Gastrohepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Ting Lin
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan.,Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Hong Tsai
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan.,Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Chien Chou
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsin-An Hou
- Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Yi Huang
- Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Ju Wu
- Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yao-Chang Chen
- Centre of Stem Cell and Precision Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Hwei-Fang Tien
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan
| | - Jih-Luh Tang
- Tai-Cheng Stem Cell Therapy Centre, National Taiwan University, Taipei, Taiwan.,Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Bor-Sheng Ko
- Division of Haematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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29
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Lewalle P, Pochon C, Michallet M, Turlure P, Brissot E, Paillard C, Puyade M, Roth-Guepin G, Yakoub-Agha I, Chantepie S. [Prophylaxis of infections post-allogeneic transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Bull Cancer 2019; 106:S23-S34. [PMID: 30616839 DOI: 10.1016/j.bulcan.2018.08.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/19/2018] [Accepted: 08/27/2018] [Indexed: 02/07/2023]
Abstract
Allogeneic hematopoietic stem cell transplantation is a curative treatment for many hematological diseases. However, this procedure causes the patient to be susceptible to infection. Prophylactic treatments are administered in clinical practice even thought the level of evidence of their effectiveness is not always high. In addition, changes in the transplantation procedures - use of reduced intensity conditioning, development of alternative graft sources - must lead to a rethinking of attitudes towards prophylaxis. Our working group based its recommendations on a review of referential articles and publications on the subject found in the literature. These recommendations concern the prophylaxis of infections caused by HSV1, HSV2, varicella zoster, and hepatitis B, as well as anti-bacterial and digestive decontamination prophylaxis, prevention of pneumocystis, toxoplasmosis, tuberculosis, as well as prophylaxis of fungal infections. Other infectious agents usually involved in infections post-allotransplant have been the subject of another set of recommendations from the French Society of Bone Marrow Transplantation and Cellular Therapy.
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Affiliation(s)
- Philippe Lewalle
- Institut Jules-Bordet, université Libre-de-Bruxelles, service d'hématologie, 1, rue Héger-Bordet, 1000 Bruxelles, Belgique
| | - Cécile Pochon
- CHU de Nancy, service d'onco-hématologie pédiatrique, rue du Morvan, 54511 Vandoeuvre-lès-Nancy, France
| | | | - Pascal Turlure
- Centre hospitalier universitaire, service d'hématologie, 87042 Limoges, France
| | - Eolia Brissot
- Assistance publique des hôpitaux de Paris (AP-HP), hôpital Saint-Antoine, département d'hématologie, 75012 Paris, France
| | | | - Mathieu Puyade
- CHU de Poitiers, service de médecine interne, unité d'hospitalisation d'aval, 2, rue de la Milétrie, 86021 Poitiers cedex, France
| | | | - Ibrahim Yakoub-Agha
- CHRU de Lille, service des maladies du sang, 2, avenue Oscar-Lambret, 59037 Lille cedex, France; Université de Lille 2, LIRIC, Inserm U995, 59000 Lille, France
| | - Sylvain Chantepie
- Institut d'hématologie de Basse-Normandie, centre hospitalier universitaire, avenue de la Côte-de-Nacre, 14000 Caen, France.
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30
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Reactivation of Hepatitis B Virus Infection With Reverse Seroconversion Following Umbilical Cord Allogeneic Hematopoietic Cell Transplantation in a Hepatitis-B-Immune Patient: A Case Report. Transplant Proc 2019; 51:602-604. [PMID: 30879599 DOI: 10.1016/j.transproceed.2018.12.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 12/29/2018] [Indexed: 11/22/2022]
Abstract
Hepatitis B virus (HBV) reactivation in patients with prior exposure to HBV and protective levels of hepatitis B surface antibody (HBsAb) is a rare phenomenon and is termed reverse seroconversion. We describe a case of reactivation of HBV infection following reverse seroconversion in a patient who underwent umbilical cord allogeneic hematopoietic cell transplantation (UHCT). The patient developed acute hepatitis with positive hepatitis B surface antigen (HBsAg) and HBV DNA in the context of prior strongly positive HBsAb. The patient was treated with oral tenofovir and liver function tests returned to normal 3 months later. Long-term monitoring for HBV reactivation should be considered in patients with prior exposure to HBV undergoing UHCT regardless of HBsAb status.
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31
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Psoriasis: Which therapy for which patient. J Am Acad Dermatol 2019; 80:43-53. [DOI: 10.1016/j.jaad.2018.06.056] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 05/24/2018] [Accepted: 06/01/2018] [Indexed: 12/17/2022]
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32
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Izumida K, Kaneko A, Takahashi K, Kusumoto S, Narita T, Takami A, Iida S, Aoyagi K, Tanaka Y. Clinical evaluation of a novel and highly sensitive immunoassay for anti-hepatitis B core antigen using a fully automated immunochemical analyzer. Hepatol Res 2018; 48:1081-1091. [PMID: 30006955 DOI: 10.1111/hepr.13229] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 04/29/2018] [Accepted: 07/06/2018] [Indexed: 01/28/2023]
Abstract
AIM Recently, the measurement of hepatitis B surface antigen and anti-hepatitis B core antigen (HBcAb) and/or anti-hepatitis B surface antigen has been recommended before various therapies to identify patients at risk of hepatitis B virus (HBV) reactivation. However, a recent study reported that HBV reactivation occurred in HBcAb-negative patients, indicating that it is challenging to identify patients with a history of HBV infection using conventional HBcAb reagent. We developed a highly sensitive HBcAb (HBcAb-HS) assay for reducing the risk of HBV reactivation. METHODS The HBcAb-HS assay is an automated chemiluminescent enzyme immunoassay system, which is suitable for clinical use. The cut-off was set at 0.020 IU/mL from the distribution patterns of HBcAb-negative specimens, and we evaluated the performance of this assay compared with conventional reagents. RESULTS This new assay showed a 27-81-fold greater sensitivity than conventional HBcAb reagents; the quantified measurement range was from 0.005 IU/mL to 1.500 IU/mL, and it showed excellent quantitative performance and correlated well with two conventional assays, using the HBcAb-positive specimens. Moreover, it showed 100% specificity for the 469 purchased HBcAb-negative specimens. Notably, this newly developed HBcAb-HS assay showed positivity in the preserved specimens before HBV reactivation, for which conventional HBcAb reagents gave negative results, and the HBcAb-HS assay could detect the lower HBcAb levels even after intensive immunosuppressive therapies, including autologous hematopoietic stem cell transplantation. CONCLUSIONS The clinical efficacy of the newly developed, highly sensitive HBcAb assay would enable the identification of patients at risk of HBV reactivation more accurately.
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Affiliation(s)
- Kyo Izumida
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Atsushi Kaneko
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Kazuya Takahashi
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tomoko Narita
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Akiyoshi Takami
- Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Katsumi Aoyagi
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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33
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Zappulo E, Nicolini LA, Di Grazia C, Dominietto A, Lamparelli T, Gualandi F, Caligiuri P, Bruzzone B, Angelucci E, Viscoli C, Mikulska M. Efficacy of lamivudine prophylaxis in preventing hepatitis B virus reactivation in patients with resolved infection undergoing allogeneic SCT and receiving rituximab. Infection 2018; 47:59-65. [PMID: 30232604 DOI: 10.1007/s15010-018-1214-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 09/04/2018] [Indexed: 01/14/2023]
Abstract
PURPOSE Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection. METHODS Patients who received first allogeneic SCT in years 2009-2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up. RESULTS Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3-97); median virological follow-up 16 months (range 0.3-78), and median length of LAM prophylaxis of 14.5 months (range 0.3-78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis. CONCLUSIONS In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.
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Affiliation(s)
- Emanuela Zappulo
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy.,Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Largo R. Benzi 10, 16132, Genoa, Italy.,Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Laura Ambra Nicolini
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy.,Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Largo R. Benzi 10, 16132, Genoa, Italy
| | - Carmen Di Grazia
- Division of Hematology and Bone Marrow Transplantation, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | - Alida Dominietto
- Division of Hematology and Bone Marrow Transplantation, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | - Teresa Lamparelli
- Division of Hematology and Bone Marrow Transplantation, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | - Francesca Gualandi
- Division of Hematology and Bone Marrow Transplantation, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | | | - Bianca Bruzzone
- Hygiene Unit, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | - Emanuele Angelucci
- Division of Hematology and Bone Marrow Transplantation, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy
| | - Claudio Viscoli
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy.,Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Largo R. Benzi 10, 16132, Genoa, Italy
| | - Malgorzata Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy. .,Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Largo R. Benzi 10, 16132, Genoa, Italy.
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34
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Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Köksal AŞ, Köksal İ, Örmeci N, Tabak F. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2018; 29:259-269. [PMID: 29755010 PMCID: PMC6284666 DOI: 10.5152/tjg.2018.18263] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 04/07/2018] [Indexed: 12/12/2022]
Abstract
This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to an emergency risk of hepatitis B reactivation. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.
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Affiliation(s)
- Bilgehan Aygen
- Department of Infectious Diseases and Clinical Microbiology, Erciyes University School of Medicine, Kayseri, Turkey
| | - Ahmet Muzaffer Demir
- Division of Hematology, Department of Internal Diseases, Trakya University School of Medicine, Edirne, Turkey
| | - Mahmut Gümüş
- Division of Oncology, Department of Internal Diseases, İstanbul Medeniyet University School of Medicine, İstanbul, Turkey
| | - Oğuz Karabay
- Department of Infectious Diseases and Clinical Microbiology, Sakarya University School of Medicine, Sakarya, Turkey
| | - Sabahattin Kaymakoğlu
- Division of Gastroenterology, Department of Internal Diseases, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Aydın Şeref Köksal
- Division of Gastroenterology, Department of Internal Diseases, Sakarya University School of Medicine, Sakarya, Turkey
| | - İftihar Köksal
- Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University School of Medicine, Trabzon, Turkey
| | - Necati Örmeci
- Division of Gastroenterology, Department of Internal Diseases, Ankara University School of Medicine, Ankara, Turkey
| | - Fehmi Tabak
- Department of Infectious Diseases and Clinical Microbiology, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
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Cholongitas E, Haidich AB, Apostolidou-Kiouti F, Chalevas P, Papatheodoridis GV. Hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive patients receiving immunosuppressive therapy: a systematic review. Ann Gastroenterol 2018; 31:480-490. [PMID: 29991894 PMCID: PMC6033767 DOI: 10.20524/aog.2018.0266] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 02/27/2018] [Indexed: 12/17/2022] Open
Abstract
Background: The optimal management of HBsAg-negative, anti-HBc-positive patients who receive immunosuppression remains unclarified. We systematically reviewed the available data on potential predictors of the risk of hepatitis B virus (HBV) reactivation in such patients. Methods: A literature search identified 55 studies with 3640 HBsAg-negative, anti-HBc-positive patients who received immunosuppressive regimens. Results: HBV reactivation was reported in 236 (6.5%) patients. The pooled HBV reactivation rates did not differ between patients with detectable or undetectable HBV DNA in studies with hematological diseases or regimens containing rituximab, but it was higher in patients with detectable than in those with undetectable HBV DNA who were taking rituximab-free regimens (14% vs. 2.6%; risk ratio [RR] 12.67, 95% CI: 95%CI 2.39-67.04, P=0.003) or had non-hematological diseases, although the latter was not confirmed by sensitivity analysis (RR 8.80, 95%CI 0.71-109.00, P=0.09). The pooled HBV reactivation rates were lower in patients with positive than in those with negative anti-HBs in studies with hematological (7.1% vs. 21.8%; RR 0.29, 95%CI 0.19-0.46, P<0.001) or non-hematological (2.5% vs. 10.7%; RR 0.28, 95%CI 0.11-0.76, P=0.012) diseases, and rituximab-containing (6.6% vs. 19.8%; RR 0.32, 95%CI 0.15-0.69, P=0.003) or rituximab-free (3.3% vs. 9.2%; RR 0.36, 95%CI 0.14-0.96, P=0.042) regimens. Conclusions: The risk of HBV reactivation is high; therefore, anti-HBV prophylaxis should be recommended in HBsAg-negative, anti-HBc-positive patients with hematological diseases and/or rituximab-containing regimens, regardless of HBV DNA and anti-HBs status. In contrast, patients with non-hematological diseases or rituximab-free regimens have a low risk of HBV reactivation and may not require anti-HBV prophylaxis if they have undetectable HBV DNA and positive anti-HBs.
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Affiliation(s)
- Evangelos Cholongitas
- 1st Department of Internal Medicine, Medical School of National & Kapodistrian University, Athens (Evangelos Cholongitas), Greece
| | - Anna-Bettina Haidich
- Department of Hygiene and Epidemiology, Medical School of Aristotle University of Thessaloniki (Anna-Bettina Haidich, Fani Apostolidou-Kiouti), Greece
| | - Fani Apostolidou-Kiouti
- Department of Hygiene and Epidemiology, Medical School of Aristotle University of Thessaloniki (Anna-Bettina Haidich, Fani Apostolidou-Kiouti), Greece
| | - Parthenis Chalevas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki (Parthenis Chalevas), Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens (George V. Papatheodoridis), Greece
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[Spontaneous remission of HCV infection after autologous stem cell transplantation in a 58-year-old man]. Internist (Berl) 2018; 58:621-625. [PMID: 28235985 DOI: 10.1007/s00108-017-0206-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
We report about a 58-year-old man with a chronic and treatment-naive hepatitis C virus (HCV) infection of genotype 1b, who had undergone autologous stem cell transplantation twice due to multiple myeloma. Subsequently, a high-level viremic reactivation of an occult hepatitis B virus (HBV) infection and also a reverse seroconversion was observed. Furthermore, a sustained spontaneous remission of HCV infection was seen. Antiviral therapy of HBV infection was initiated with tenofovir. Seven months after therapy initiation, the patient acquired an "anti-HBc-only" status. Antiviral therapy with tenofovir is still continued. The patient is in a good clinical condition.
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Nicolini LA, Zappulo E, Viscoli C, Mikulska M. Management of chronic viral hepatitis in the hematological patient. Expert Rev Anti Infect Ther 2018; 16:227-241. [PMID: 29415584 DOI: 10.1080/14787210.2018.1438264] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Infection with HBV and HCV represents a growing challenge in the management of patients with hematological malignancies. Recently, hepatitis E (HEV) was recognized as an endemic infection in developed countries and as an emerging health problem in immunocompromised patients. Areas covered: We reviewed the current knowledge on the impact of chronic viral hepatitis in the hematological setting. Epidemiological features, screening strategies and indications for treatment and monitoring have been explored and commented. Expert commentary: Knowing patient's complete HBV serostatus is mandatory in order to choose between treatment, prophylaxis or a pre-emptive approach. Recent guidelines favor treatment with high barrier molecules in all patients with chronic HBV infection and long lasting prophylaxis with those with inactive or resolved one. With regard to HCV, the new direct-acting antiviral agents have been safely administered in the hematological setting. Their use as first-line single treatment in indolent lymphomas, and combined with chemotherapy in aggressive ones, should be considered. Due to the existing risk of chronic HEV infection in the immunocompromised, screening with serum HEV-RNA should be performed in case of signs and symptoms indicative of hepatitis. In the event of HEV infection, reduction of immunosuppression and, if not feasible or unsuccessful, ribavirin treatment should be prescribed.
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Affiliation(s)
- Laura Ambra Nicolini
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
| | - Emanuela Zappulo
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy.,b Division of Infectious Diseases, Department of Clinical Medicine and Surgery , University of Naples Federico II , Naples , Italy
| | - Claudio Viscoli
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
| | - Malgorzata Mikulska
- a Infectious Diseases Unit, Department of Health Science (DISSAL), Ospedale Policlinico San Martino, IRCCS per l'Oncologia , University of Genoa , Genoa , Italy
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Anastasiou OE, Almpani F, Herrmann A, Gerken G, Ditschkowski M, Ciesek S. HBV reactivation in allogeneic stem cell transplant recipients: Risk factors, outcome, and role of hepatitis B virus mutations. Hepatol Commun 2017; 1:1014-1023. [PMID: 29404439 PMCID: PMC5721402 DOI: 10.1002/hep4.1118] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 10/03/2017] [Accepted: 10/04/2017] [Indexed: 01/25/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation (HBVr) in recipients of allogeneic hematopoetic stem cells (aHSCs) appears heterogeneously with respect to its frequency, manifestation, and outcome. The aim of this study was to present data from a large German cohort of recipients of aHSC transplantation (aHSCT), focusing on the incidence of HBVr in antibody to hepatitis B core antigen (anti-HBc)-positive aHSCT recipients, its clinical outcome, and the role of mutations in HBV. Between 2005 and 2015, 1,871 patients received aHSCT at University Hospital Essen. A follow-up of at least 6 months after transplant was available in 55 patients who were anti-HBc-positive; clinical and virologic data were analyzed. The HBV genome was sequenced with next generation technology from serum samples of 8 patients with HBVr. Thirteen out of 55 (23.6%) patients developed HBVr at a median of 26 months after aHSCT. After initiation of antiviral treatment, complete HBV DNA suppression was achieved in 7/10 (70%) patients 1 to 40 months after HBVr. Nine of 13 patients had increased alanine aminotransferase; 3 patients had compromised coagulation and model for end-stage liver disease scores of 18-27, and 1 of these patients died due to liver failure 5 weeks after HBVr. As a risk factor for HBVr, we identified anti-HBc signal to cut-off ration (S/CO) ≥7.5 before transplantation. Complete HBV DNA suppression was achieved in 7/10 patients; therapy-relevant mutations were found in 1 patient. In 4/8 patients, immune escape mutations were detected either as majority or minority variants. Conclusion: HBVr is common in anti-HBc-positive aHRCT recipients and can lead to severe hepatitis with compromised coagulation. The level of anti-HBc S/CO before transplantation is a risk factor for HBVr. Complete virologic response under adequate antiviral treatment could not be achieved in all patients. (Hepatology Communications 2017;1:1014-1023).
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Affiliation(s)
- Olympia E. Anastasiou
- Institute of Virology, University Hospital EssenUniversity Duisburg‐EssenEssenGermany
- Department of Gastroenterology and HepatologyUniversity Hospital of EssenEssenGermany
| | - Foteini Almpani
- Institute of Virology, University Hospital EssenUniversity Duisburg‐EssenEssenGermany
| | - Anke Herrmann
- Institute of Virology, University Hospital EssenUniversity Duisburg‐EssenEssenGermany
| | - Guido Gerken
- Department of Gastroenterology and HepatologyUniversity Hospital of EssenEssenGermany
| | - Markus Ditschkowski
- Department of Bone Marrow TransplantationUniversity Hospital of EssenEssenGermany
| | - Sandra Ciesek
- Institute of Virology, University Hospital EssenUniversity Duisburg‐EssenEssenGermany
- German Center for Infection ResearchEssenGermany
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Fan XP, Dou CY, Fan YC, Cao CJ, Zhao ZH, Wang K. Methylation status of the estrogen receptor 1 promoter predicts poor prognosis of acute-on-chronic hepatitis B liver failure. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:818-827. [PMID: 29082740 DOI: 10.17235/reed.2017.4426/2016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. AIMS To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. METHODS Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. RESULTS Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. CONCLUSIONS Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF.
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Affiliation(s)
- Xiao-Peng Fan
- Department of Hepatology, Qilu Hospital of Shandong University
| | - Cheng-Yun Dou
- Department of Hepatology, Qilu Hospital of Shandong University
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University;Hepatology Institute of Shandong University
| | - Chuang-Jie Cao
- Department of Pathology, the first affiliated hospital of Sun Yat-san University
| | - Ze-Hua Zhao
- Department of Hepatology, Qilu Hospital of Shandong University
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, China
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40
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Choi J, Lim YS. Characteristics, Prevention, and Management of Hepatitis B Virus (HBV) Reactivation in HBV-Infected Patients Who Require Immunosuppressive Therapy. J Infect Dis 2017; 216:S778-S784. [PMID: 29156044 DOI: 10.1093/infdis/jix178] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation becomes a challenging issue with increasing use of immunosuppressive agents and cytotoxic chemotherapy for varied medical conditions, including cancer. The spectrum of HBV reactivation in the setting of immunosuppression may vary from asymptomatic reactivation to liver failure leading to death. HBV reactivation can hamper the course of planned therapies and diminish the effects of therapies; thus, it adversely affects the prognosis of the original disease and the survival of the patients. There is mounting evidence that HBV reactivation can be prevented and managed if patients are screened to determine their risk for HBV reactivation and are treated prophylactically before therapy with immunosuppressive agents or cytotoxic chemotherapy is initiated. In this article, we review the diagnostic criteria and clinical outcomes of HBV reactivation, discuss how immunosuppressive therapy may influence the risk of HBV reactivation, and outline strategies to prevent HBV reactivation.
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Affiliation(s)
- Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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41
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Chronic Hepatitis B, C, and D. Microbiol Spectr 2017; 4. [PMID: 27726758 DOI: 10.1128/microbiolspec.dmih2-0025-2015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.
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42
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Gentile G, Andreoni M, Antonelli G, Sarmati L. 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 2017; 23:916-923. [PMID: 28668465 DOI: 10.1016/j.cmi.2017.06.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/15/2017] [Accepted: 06/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The growth of new therapeutic options and practices increases the risk of hepatitis B virus (HBV) reactivation in patients with haematologic malignancies and/or patients undergoing haematologic stem cell transplantation (HSCT). OBJECTIVES To provide a systematic review supporting recommendations for prevention, monitoring, prophylaxis and therapy of HBV reactivation in patients with haematologic malignancies and HSCT. DATA SOURCES The systematic review was based on a strategy using PubMed and the Cochrane Library searching literature published from 1991 to December 31, 2016. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed. SELECTION CRITERIA Randomized control trials, prospective and retrospective cohort studies. RISK-OF-BIAS ASSESSMENT Cochrane Risk of Bias Tool and Newcastle Ottawa Quality Assessment Scale. RESULTS Forty-two studies of fair or good quality were included in this systematic review. The following main results were obtained: haematologic patients should be screened for HBV before chemotherapy; HBV DNA levels should be monthly monitored in all HBV-positive patients not receiving prophylaxis; hepatitis B surface antigen (HBsAg)-positive haematologic patients and patients undergoing HSCT should receive prophylaxis and third-generation HBV drugs should be provided; and anti-hepatitis B core protein-positive lymphoma patients and patients who underwent HSCT should receive antiviral prophylaxis. CONCLUSIONS A higher quality of evidence is needed. However, the level of evidence was sufficient to support the recommendations published in this issue of the journal.
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Affiliation(s)
- G Gentile
- Department of Cellular Biotechnologies and Haematology, La Sapienza University, Rome, Italy
| | - M Andreoni
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy
| | - G Antonelli
- Department of Molecular Medicine, La Sapienza University, Rome, Italy
| | - L Sarmati
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy.
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43
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Seto WK, Chan TSY, Hwang YY, Wong DKH, Fung J, Liu KSH, Gill H, Lam YF, Lau EHY, Cheung KS, Lie AKW, Lai CL, Kwong YL, Yuen MF. Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study. Hepatology 2017; 65:1451-1461. [PMID: 28027590 DOI: 10.1002/hep.29022] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 10/10/2016] [Accepted: 12/22/2016] [Indexed: 12/15/2022]
Abstract
UNLABELLED Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. CONCLUSION HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Thomas Sau-Yan Chan
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yu-Yan Hwang
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Danny Ka-Ho Wong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Kevin Sze-Hang Liu
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Harinder Gill
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yuk-Fai Lam
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Eric H Y Lau
- School of Public Health, The University of Hong Kong, Hong Kong
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Albert K W Lie
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yok-Lam Kwong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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Varma A, Biritxinaga L, Saliba RM, Stich M, Jauch SF, Afrough A, Honhar M, Popat UR, Shafi MA, Shah N, Bashir Q, Dinh Y, Hosing C, Champlin RE, Qazilbash MH. Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant 2017; 23:581-587. [PMID: 28063964 PMCID: PMC5749257 DOI: 10.1016/j.bbmt.2017.01.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 01/01/2017] [Indexed: 01/01/2023]
Abstract
Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.
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Affiliation(s)
- Ankur Varma
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas
| | - Laura Biritxinaga
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rima M Saliba
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Maximilian Stich
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sarah Francesca Jauch
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Aimaz Afrough
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Medhavi Honhar
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Uday R Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mehnaz A Shafi
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Nina Shah
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Qaiser Bashir
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yvonne Dinh
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Chitra Hosing
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Richard E Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Muzaffar H Qazilbash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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45
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Occult Hepatitis B Virus Reactivation in a Seronegative Stem Cell Transplant Recipient. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2017. [DOI: 10.1097/ipc.0000000000000472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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46
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Guarino M, Picardi M, Vitiello A, Pugliese N, Rea M, Cossiga V, Pane F, Caporaso N, Morisco F. Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma. Ann Hepatol 2017. [DOI: 10.5604/16652681.1231579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
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Wang Q, Klenerman P, Semmo N. Significance of anti-HBc alone serological status in clinical practice. Lancet Gastroenterol Hepatol 2017; 2:123-134. [DOI: 10.1016/s2468-1253(16)30076-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 07/26/2016] [Accepted: 07/29/2016] [Indexed: 02/07/2023]
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48
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Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis: a retrospective analysis. Int Urol Nephrol 2016; 49:475-482. [PMID: 28032257 DOI: 10.1007/s11255-016-1487-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 12/09/2016] [Indexed: 12/18/2022]
Abstract
PURPOSE The aim of this study is to investigate the prevalence and risk factors for hepatitis B virus (HBV) reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis. METHODS We performed a retrospective study of 745 HBsAg-negative/HBcAb-positive patients undergoing immunosuppressive therapy for glomerulonephritis from years 2003 to 2012 at the department of nephrology, China-Japan Friendship Hospital, Beijing, China. The patients were divided into HBV reactivation group (n = 27) and non-HBV reactivation group (n = 718). RESULTS The prevalence of HBV reactivation in patients receiving immunosuppressive therapy for glomerulonephritis was up to 3.62% in serological status of HBsAg-negative/HBcAb-positive. HBV reactivation was associated with several findings: greater proportion of lupus nephritis (25.93 vs. 9.61%, p = 0.014), much higher percentage of HBsAb-negative (74.07 vs. 23.82%, p < 0.001), longer duration of immunosuppressive treatment (100 vs. 70.06%, p < 0.001), as well as more cases of combined immunosuppressant (92.59 vs. 61.56%, p = 0.001). After univariate and multivariate analysis, three variables remained as independent risk factors for HBV reactivation: serological status of HBsAb-negative (OR 8.375, 95% CI 3.674-19.776, p = 0.001), length of immunosuppressive treatment more than 1 year (OR 1.308, 95% CI 1.121-1.358, p = 0.024), and combined immunosuppressant (OR 6.342, 95% CI 1.675-30.166, p = 0.003). CONCLUSIONS HBV reactivation is not uncommon in HBsAg-negative/HBcAb-positive glomerulonephritis patients treated with immunosuppressant, and the prevalence was up to 3.62%. Patients with serological status of HBsAb-negative, more than 1 year of immunosuppressive therapy, and combined immunosuppressant are independent risk factors for HBV reactivation.
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49
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Fedele R, Salooja N, Martino M. Recommended screening and preventive evaluation practices of adult candidates for hematopoietic stem cell transplantation. Expert Opin Biol Ther 2016; 16:1361-1372. [DOI: 10.1080/14712598.2016.1229773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Krüger W, Mousset S, Neuburger S, Neumann S, Penack O, Silling G, Vehreschild JJ, Einsele H, Maschmeyer G. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol 2016; 95:1435-55. [PMID: 27339055 PMCID: PMC4972852 DOI: 10.1007/s00277-016-2711-1] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/28/2016] [Indexed: 12/13/2022]
Abstract
Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.
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Affiliation(s)
- Andrew J Ullmann
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
| | - Martin Schmidt-Hieber
- Clinic for Hematology, Oncology und Tumor Immunology, Helios Clinic Berlin-Buch, Berlin, Germany
| | - Hartmut Bertz
- Department of Hematology/Oncology, University of Freiburg Medical Center, 79106, Freiburg, Germany
| | - Werner J Heinz
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
| | - Michael Kiehl
- Medical Clinic I, Klinikum Frankfurt (Oder), Frankfurt (Oder), Germany
| | - William Krüger
- Haematology and Oncology, Stem Cell Transplantation, Palliative Care, University Hospital Greifswald, Greifswald, Germany
| | - Sabine Mousset
- Medizinische Klinik III, Palliativmedizin und interdisziplinäre Onkologie, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Stefan Neuburger
- Sindelfingen-Böblingen Clinical Centre, Medical Department I, Division of Hematology and Oncology, Klinikverbund Südwest, Sindelfingen, Germany
| | | | - Olaf Penack
- Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - Gerda Silling
- Department of Internal Medicine IV, University Hospital RWTH Aachen, Aachen, Germany
| | - Jörg Janne Vehreschild
- Department I of Internal Medicine, German Centre for Infection Research, Partner-site: Bonn-Cologne, University Hospital of Cologne, Cologne, Germany
| | - Hermann Einsele
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
| | - Georg Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany
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