|
1
|
Ali FS, Nguyen MH, Hernaez R, Huang DQ, Wilder J, Piscoya A, Simon TG, Falck-Ytter Y. AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals. Gastroenterology 2025; 168:267-284. [PMID: 39863345 DOI: 10.1053/j.gastro.2024.11.008] [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] [Indexed: 01/27/2025]
Abstract
BACKGROUND & AIMS Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr. This clinical practice guideline update aims to inform frontline health care practitioners by providing evidence-based practice recommendation for the management of HBVr in at-risk individuals. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel conducted a systematic evidence review to identify new studies since publication of the first version of this clinical practice guideline in 2014. The Evidence to Decision framework was used to develop recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBVr. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 4 recommendations. Based on evidence and baseline risk assessment, the panel made a strong recommendation in favor of antiviral prophylaxis for individuals at high risk of HBVr. For individuals at moderate risk of HBVr, a conditional recommendation was made in favor of antiviral prophylaxis. For individuals at low risk of HBVr, a conditional recommendation was made in favor of monitoring alone without antiviral prophylaxis. Monitoring should be performed at 1- to 3-month intervals, and must include assessment of hepatitis B viral load in addition to assessment of alanine aminotransferase. For individuals deemed to be at-risk of HBVr, the panel agreed on a strong recommendation in favor of testing for HBV; given universal Centers for Disease Control and Prevention screening guidance for hepatitis B for all adults 18 years and older by testing for HBV surface antigen, hepatitis B surface antibody, and total hepatitis B core antibody, stratifying screening practices by magnitude of HBVr risk is no longer needed. CONCLUSIONS This document provides updated guidance for the management of HBVr in at-risk individuals. Limitations and gaps in the evidence are highlighted. This guideline is expected to require updating in 5 years from publication.
Collapse
Affiliation(s)
- Faisal S Ali
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California; Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, California
| | - Ruben Hernaez
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Julius Wilder
- Division of Gastroenterology, Duke Department of Medicine, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina
| | - Alejandro Piscoya
- School of Medicine, Universidad Tecnológica del Peru (UTP), Lima, Peru
| | - Tracey G Simon
- Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Yngve Falck-Ytter
- Section of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Health Care System, Cleveland, Ohio; Division of Gastroenterology and Hepatology, Case Western Reserve University, Cleveland, Ohio
| |
Collapse
|
|
2
|
Huang SW, Long H, Huang JQ. Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention. Pathogens 2024; 14:8. [PMID: 39860969 PMCID: PMC11768139 DOI: 10.3390/pathogens14010008] [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: 11/05/2024] [Revised: 12/25/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up.
Collapse
Affiliation(s)
- Shuai-Wen Huang
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
- Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China
| | - Hong Long
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
| | - Jia-Quan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;
| |
Collapse
|
|
3
|
Deepan N, Maung ST, Decharatanachart P, Chaiteerakij R. Hepatitis B Virus Reactivation in Cancer Patients Receiving Chemotherapy-A Systematic Review and Meta-Analysis. Semin Oncol 2024; 51:123-134. [PMID: 39537474 DOI: 10.1053/j.seminoncol.2024.08.001] [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: 01/10/2024] [Revised: 07/14/2024] [Accepted: 08/04/2024] [Indexed: 11/16/2024]
Abstract
Hepatitis B virus (HBV) reactivation is a critical concern for patients with a diagnosis of cancer receiving chemotherapy worldwide. Our aim was to assess the rate of HBV reactivation during chemotherapy globally. We systematically reviewed PubMed, Embase, Scopus, and Google Scholar databases for chemotherapy-related HBV reactivation studies from inception until July 2023. A random-effects model was used to estimate the pooled reactivation rate. Total 86 studies involving 21,297 patients were included, comprising 62 and 24 studies from Eastern and Western regions. Pooled results indicated a 9% reactivation rate (95%CI: 7%-13%, I2 = 95%). Reactivation rates were 10% (95%CI: 7%-14%, I2 = 92%) for hematological malignancies and 5% (95%CI: 3%-9%, I2 = 94%) for solid tumors. Presence of HBV DNA, HBeAg, and HBsAg were correlated with reactivation rates of 29% (95%CI: 10%-60%, I2 = 91%), 23% (95%CI: 14%-36%, I2 = 78%), and 15% (95%CI: 11%-20%, I2 = 90%), respectively. For patients with positive anti-HBe Ab, anti-HBc, and anti-HBs Ab serology, pooled reactivation rates were 7% (95%CI: 3%-14%, I2 = 81%), 4% (95%CI: 3%-7%, I2 = 85%), and 3% (95%CI: 2%-6%, I2 = 80%), respectively. With antiviral prophylaxis, reactivation rates were 1% (95%CI: 0%-17%, I2 = 59%), 1% (95%CI: 0%-5%, I2 = 0%), 4% (95%CI: 2%-9%, I2 = 85%), and 6% (95%CI: 3%-12%, I2 = 32%) for patients receiving tenofovir, entecavir, lamivudine, and telbivudine, respectively. Patients with a diagnosis of cancer undergoing chemotherapy face increased risk of HBV reactivation. This analysis raises public awareness and serves as a resource for future clinical trials.
Collapse
Affiliation(s)
- Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Soe Thiha Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
| |
Collapse
|
|
4
|
Chen S, Li B, Luo W, Rehman AU, He M, Yang Q, Wang S, Guo J, Chen L, Li X. Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication. J Clin Transl Hepatol 2024; 12:457-468. [PMID: 38779518 PMCID: PMC11106347 DOI: 10.14218/jcth.2023.00537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/18/2024] [Accepted: 02/19/2024] [Indexed: 05/25/2024] Open
Abstract
Background and Aims Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment. Methods The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice. Results PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota. Conclusions PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.
Collapse
Affiliation(s)
- Shi Chen
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Benhua Li
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Wei Luo
- Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Adeel ur Rehman
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Miao He
- Laboratory Animal Center of Chongqing Medical University, Chongqing, China
| | - Qian Yang
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Shunyao Wang
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jinjun Guo
- Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Chongqing, China
| | - Ling Chen
- The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing, China
| | - Xiaosong Li
- Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
5
|
Kumar N, Choudhary NS. Managing HBV and HCV Infection Pre- and Post-liver Transplant. J Clin Exp Hepatol 2024; 14:101287. [PMID: 38076445 PMCID: PMC10709521 DOI: 10.1016/j.jceh.2023.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 09/19/2023] [Indexed: 03/03/2025] Open
Abstract
Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.
Collapse
Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
| | | |
Collapse
|
|
6
|
Yang J, Zheng L, Yang Z, Wei Z, Shao J, Zhang Y, Yao J, Li M, Wang X, Zheng M. 5-FU promotes HBV replication through oxidative stress-induced autophagy dysfunction. Free Radic Biol Med 2024; 213:233-247. [PMID: 38215891 DOI: 10.1016/j.freeradbiomed.2024.01.011] [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: 08/15/2023] [Revised: 12/27/2023] [Accepted: 01/08/2024] [Indexed: 01/14/2024]
Abstract
BACKGROUND & AIMS Hepatitis B virus (HBV) reactivation is a major problem that must be overcome during chemotherapy for HBV-related hepatocellular carcinoma (HCC). However, the mechanism underlying chemotherapy-associated HBV reactivation is still not fully understood, hindering the development of improved HBV-related HCC treatments. METHODS A meta-analysis was performed to assess the HBV reactivation risk during transcatheter arterial chemoembolization (TACE). To investigate the regulatory effects and mechanisms of 5-FU on HBV replication, an HBV mouse model was established by pAAV-HBV1.2 hydrodynamic injection followed by intraperitoneal 5-FU injection, and different in vitro models (HepG2.2.15 or Huh7 cells) were established. Realtime RT‒qPCR, western blotting, luciferase assays, and immunofluorescence were used to determine viral parameters. We also explored the underlying mechanisms by RNA-seq, oxidative stress evaluation and autophagy assessment. RESULTS The pooled estimated rate of HBV reactivation in patients receiving TACE was 30.3 % (95 % CI, 23.1%-37.4 %). 5-FU, which is a chemotherapeutic agent commonly used in TACE, promoted HBV replication in vitro and in vivo. Mechanistically, 5-FU treatment obviously increased autophagosome formation, as shown by increased LC3-II levels. Additionally, 5-FU impaired autophagic degradation, as shown by marked p62 and mCherry-GFP-LC3 upregulation, ultimately promoting HBV replication and secretion. Autophagy inhibition by 3-methyladenine or chloroquine significantly altered 5-FU-induced HBV replication. Furthermore, 5-FU-induced autophagy and HBV replication were markedly attenuated with a reactive oxygen species (ROS) scavenger. CONCLUSIONS Together, our results indicate that ROS-induced autophagosome formation and autophagic degradation play a critical role in 5-FU-induced HBV reactivation.
Collapse
Affiliation(s)
- Jing Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Luyan Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Zhenggang Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Zhiqiang Wei
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jiajia Shao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yina Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jiping Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Minwei Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Xueyu Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
| | - Min Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
| |
Collapse
|
|
7
|
Tsuji D, Nakagaki S, Yonezawa I, Suzuki K, Yokokawa T, Kawasaki Y, Yamaguchi T, Kawaguchi T, Hatori M, Matsumoto T, Sakata Y, Yamamoto K, Nishimura T, Kogure Y, Hayashi T, Osawa M, Itoh K, Watanabe M. A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I. Invest New Drugs 2024; 42:44-52. [PMID: 38055127 DOI: 10.1007/s10637-023-01414-y] [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: 10/17/2023] [Accepted: 11/22/2023] [Indexed: 12/07/2023]
Abstract
Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.
Collapse
Affiliation(s)
- Daiki Tsuji
- Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
| | - Shigeru Nakagaki
- Department of Pharmacy, Shizuoka General Hospital, Shizuoka, Japan
| | - Itsuki Yonezawa
- Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
| | - Kenichi Suzuki
- Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Takashi Yokokawa
- Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yohei Kawasaki
- Faculty of Nursing, Japanese Red Cross College of Nursing, Tokyo, Japan
| | - Takumi Yamaguchi
- Institute for Assistance of Academic and Education, IAAE, Kanagawa, Japan
| | - Takashi Kawaguchi
- Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Masahiro Hatori
- Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takuma Matsumoto
- Pharmaceutical Department, National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan
| | - Yukio Sakata
- Department of Pharmacy, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Keisuke Yamamoto
- Department of Pharmacy, Seirei Hamamatsu General Hospital, Shizuoka, Japan
| | - Tomoyasu Nishimura
- Department of Pharmacy, Wakayama Medical University Hospital, Wakayama, Japan
| | - Yuki Kogure
- Department of Pharmacy, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
| | - Toshinobu Hayashi
- Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Misa Osawa
- Department of Pharmacy, Shizuoka General Hospital, Shizuoka, Japan
| | - Kunihiko Itoh
- Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
| | - Masaya Watanabe
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| |
Collapse
|
|
8
|
Mizuno J, Urabe Y, Oka S, Konishi H, Ishibashi K, Fukuhara M, Tanaka H, Tsuboi A, Yamashita K, Hiyama Y, Kotachi T, Takigawa H, Yuge R, Hiyama T, Tanaka S. Predictive factors for esophageal stenosis in patients receiving prophylactic steroid therapy after endoscopic submucosal dissection for esophageal squamous cell carcinoma. BMC Gastroenterol 2024; 24:41. [PMID: 38245690 PMCID: PMC10799525 DOI: 10.1186/s12876-024-03135-9] [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: 08/02/2023] [Accepted: 01/15/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC. METHODS Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. RESULTS Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. CONCLUSIONS Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.
Collapse
Affiliation(s)
- Junichi Mizuno
- Department of Gastroenterology, Graduate School of Biomedical & Science, Hiroshima University, Hiroshima, Japan
| | - Yuji Urabe
- Department of Gastrointestinal Endoscopy and Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical & Science, Hiroshima University, Hiroshima, Japan
| | - Hirona Konishi
- Department of Gastroenterology, Graduate School of Biomedical & Science, Hiroshima University, Hiroshima, Japan
| | - Kazuki Ishibashi
- Department of Gastroenterology, Graduate School of Biomedical & Science, Hiroshima University, Hiroshima, Japan
| | - Motomitsu Fukuhara
- Department of Gastroenterology, Graduate School of Biomedical & Science, Hiroshima University, Hiroshima, Japan
| | - Hidenori Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Akiyoshi Tsuboi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Ken Yamashita
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Yuichi Hiyama
- Department of Hiroshima Clinical Research and Development Support Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Takahiro Kotachi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| |
Collapse
|
|
9
|
Mak JWY, Law AWH, Law KWT, Ho R, Cheung CKM, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol 2023; 29:4942-4961. [PMID: 37731995 PMCID: PMC10507505 DOI: 10.3748/wjg.v29.i33.4942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/22/2023] [Accepted: 08/15/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
Collapse
Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | | | | | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong 852, China
| | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| |
Collapse
|
|
10
|
Kim DY, Kim YR, Suh C, Yoon DH, Yang DH, Park Y, Eom HS, Lee JO, Kwak JY, Kang HJ, Hyun SY, Jo JC, Chang MH, Yoo KH, Lim SN, Shin HJ, Kim WS, Kim IH, Kim MK, Kim HJ, Lee WS, Mun YC, Kim JS. A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. Am J Gastroenterol 2023; 118:1373-1380. [PMID: 36728217 DOI: 10.14309/ajg.0000000000002185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/28/2022] [Indexed: 02/03/2023]
Abstract
INTRODUCTION This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). DISCUSSION Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).
Collapse
Affiliation(s)
- Do Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Yu Ri Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Cheolwon Suh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dok Hyun Yoon
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Hwan Yang
- Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea
| | - Yong Park
- Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Hyeon Seok Eom
- Hematology-Oncology Clinic, National Cancer Center, Goyang, Korea
| | - Jeong-Ok Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae-Yong Kwak
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
| | - Hye Jin Kang
- Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Shin Young Hyun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae-Cheol Jo
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Myung Hee Chang
- Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
| | - Kwai Han Yoo
- Departments of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Ho-Jin Shin
- Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea
| | - Won Seog Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - In-Ho Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Min Kyung Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Won-Sik Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Yeung-Chul Mun
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| |
Collapse
|
|
11
|
Song Y, Tilly H, Rai S, Zhang H, Jin J, Goto H, Terui Y, Shin HJ, Kim WS, Cao J, Feng J, Eom HS, Kim TM, Tsai XCH, Gau JP, Koh H, Zhang L, Song Y, Yang Y, Li W, Huang H, Ando K, Sharman JP, Sehn LH, Bu L, Wang X, Jiang Y, Hirata J, Lee C, Zhu J, Izutsu K. Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. Blood 2023; 141:1971-1981. [PMID: 36626583 PMCID: PMC10646777 DOI: 10.1182/blood.2022017734] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/08/2022] [Accepted: 12/08/2022] [Indexed: 01/12/2023] Open
Abstract
In the phase 3 POLARIX study in previously untreated diffuse large B-cell lymphoma, polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intention-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cutoff (28 June 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population, and was superior with Pola-R-CHP vs R-CHOP (hazard ratio, 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP vs R-CHOP in the Asia and global populations in POLARIX. This trial was registered at https://clinicaltrials.gov/ct2/home as # NCT03274492.
Collapse
Affiliation(s)
- Yuqin Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Hervé Tilly
- Centre Henri Becquerel and University of Rouen, Rouen, France
| | - Shinya Rai
- Kindai University Hospital, Osaka, Japan
| | - Huilai Zhang
- Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Jie Jin
- The First Affiliated Hospital of College of Medicine, Zhejiang University, Zhejiang, China
| | - Hideki Goto
- Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
| | | | - Ho-Jin Shin
- Pusan National University Hospital, Busan, Republic of Korea
| | - Won Seog Kim
- Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Junning Cao
- Fudan University Shanghai Cancer Center, Shanghai, China
| | | | - Hyeon Seok Eom
- Center for Hematologic Malignancy, National Cancer Center, Goyang, Republic of Korea
| | - Tae Min Kim
- Seoul National University Hospital, Seoul, Republic of Korea
| | | | - Jyh-Pyng Gau
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hideo Koh
- Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Liling Zhang
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yongping Song
- Department of Hematology, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Yu Yang
- Department of Lymphoma, Head and Neck Oncology, Fujian Cancer Hospital, Fuzhou, China
| | - Wei Li
- Department of Hematology and Oncology, The First Hospital of Jilin University, Jilin, China
| | - He Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Kiyoshi Ando
- Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
| | | | - Laurie H. Sehn
- BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada
| | - Lilian Bu
- F. Hoffmann-La Roche Ltd, Shanghai, China
| | - Xin Wang
- F. Hoffmann-La Roche Ltd, Shanghai, China
| | | | | | | | - Jun Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Koji Izutsu
- National Cancer Center Hospital, Tokyo, Japan
| |
Collapse
|
|
12
|
Shui LP, Zhu Y, Duan XQ, Chen YT, Yang L, Tang XQ, Zhang HB, Xiao Q, Wang L, Liu L, Luo XH. HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) predicts a high risk of hepatitis B reactivation in patients with B-cell lymphoma receiving rituximab based immunochemotherapy. J Med Virol 2023; 95:e28549. [PMID: 36734081 DOI: 10.1002/jmv.28549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 12/30/2022] [Accepted: 01/24/2023] [Indexed: 02/04/2023]
Abstract
Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase hazard ratio [HR], 10.123; 95% confidence interval [CI], 3.389-30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684-205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.
Collapse
Affiliation(s)
- Li-Ping Shui
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Zhu
- Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiao-Qin Duan
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Ting Chen
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Yang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Qiong Tang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hong-Bin Zhang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qing Xiao
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Wang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lin Liu
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Hua Luo
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
13
|
Zhang L, Yang S, Yu Y, Wang S, Yu Y, Jin Y, Zhao A, Mao Y, Lu L. Prophylactic effect of tenofovir on viral reactivation in immunocompromised pregnant women living with hepatitis B virus. Hepatol Commun 2022; 6:2431-2440. [PMID: 35593183 PMCID: PMC9426410 DOI: 10.1002/hep4.1994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/05/2022] [Accepted: 04/25/2022] [Indexed: 02/05/2023] Open
Abstract
The appropriate prophylaxis for hepatitis B virus reactivation (HBVr) during gestation for immunocompromised pregnant women has yet to be determined. The prophylactic efficacy and safety of tenofovir disoproxil fumarate (TDF) in hepatitis B surface antigen (HBsAg)–positive patients and the HBVr risk in hepatitis B core antibody (HBcAb)–positive patients during gestation were investigated. Eligible pregnant women were diagnosed with rheumatic diseases and were administered prednisone (≤10 mg daily) with permitted immunosuppressants at screening. HBsAg‐positive participants were instructed to take TDF; those unwilling to take TDF were followed up as the control group. Propensity score matching was applied to control for differences in confounding factors between the HBcAb‐positive and uninfected groups. Hepatopathy, maternal, pregnancy, and safety outcomes were documented as endpoints. A cohort of 1292 women was recruited from 2017 to 2020, including 58 HBsAg‐positive patients (29 in each group). A total of 120 pairs in the HBcAb‐positive and noninfection groups were analyzed. Among HBsAg‐positive patients, 6 (20.7%) cases of hepatitis flare (hazard ratio [HR]: 7.44; 95% confidence interval [CI]: 1.50–36.89; p = 0.014) and 12 (41.4%) cases of HBVr (HR: 8.71; 95% CI: 2.80–27.17; p < 0.001) occurred in the control group, while 0 occurred in the TDF prophylaxis group. The HBV level at delivery was the lowest (1.6 log10 IU/ml) for those who received TDF during the pregestation period with a good safety profile. More adverse maternal outcomes were observed in the control group (odds ratio: 0.19, 95% CI: 0.05–0.77, p = 0.021), including one death from fulminant hepatitis and two cases of vertical transmission. No HBVr was recorded in HBcAb‐positive participants. Among immunocompromised pregnant women, prophylactic TDF during pregestation was necessary for HBsAg‐positive women, whereas regular monitoring was recommended for HBcAb‐positive women.
Collapse
Affiliation(s)
- Le Zhang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaoying Yang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongfu Yu
- Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Suli Wang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuetian Yu
- Department of Critical Care Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Jin
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Aimin Zhao
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yimin Mao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Institute of Digestive Disease, Shanghai, China
| | - Liangjing Lu
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
14
|
KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
|
|
15
|
Szpakowski JL, Tucker LY, Baer DM, Pauly MP. Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study. CANADIAN LIVER JOURNAL 2022; 5:43-60. [PMID: 35990784 PMCID: PMC9231429 DOI: 10.3138/canlivj-2021-0018] [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: 08/13/2021] [Accepted: 08/13/2021] [Indexed: 11/04/2023]
Abstract
BACKGROUND The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. METHODS We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. RESULTS Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). CONCLUSIONS Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.
Collapse
Affiliation(s)
| | - Lue-Yen Tucker
- Division of Research, Kaiser Permanente, Oakland, California, USA
| | - David M Baer
- Kaiser Permanente Medical Center, Oakland, California, USA
| | - Mary Pat Pauly
- Kaiser Permanente Medical Center, Sacramento, California, USA
| |
Collapse
|
|
16
|
Chang Y, Jeong SW, Jang JY. Hepatitis B Virus Reactivation Associated With Therapeutic Interventions. Front Med (Lausanne) 2022; 8:770124. [PMID: 35096867 PMCID: PMC8795508 DOI: 10.3389/fmed.2021.770124] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.
Collapse
Affiliation(s)
- Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
17
|
Immunopathogenesis of Acute Flare of Chronic Hepatitis B: With Emphasis on the Role of Cytokines and Chemokines. Int J Mol Sci 2022; 23:ijms23031407. [PMID: 35163330 PMCID: PMC8835919 DOI: 10.3390/ijms23031407] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/22/2022] [Accepted: 01/25/2022] [Indexed: 11/17/2022] Open
Abstract
Acute flares (AFs) of chronic hepatitis B usually occur during the immune-active stage (both immune clearance phase and immune reactivation phase), as the host immune system tries to control the virus. Successful host immune control over viral replication is usually presented as hepatitis B surface antigen seroclearance; however, 20–30% individuals with chronic hepatitis B may encounter repeated AFs with accumulative liver injuries, finally leading to the development of cirrhosis and hepatocellular carcinoma. AF can also develop in other clinical situations such as organ transplantation, cancer chemotherapy, and under treatment for chronic hepatitis B or treatment for chronic hepatitis C in patients with co-infected hepatitis B/hepatitis C. Understanding the natural history and immunopathogenesis of AF would help develop effective strategies to eradicate the virus and improve the clinical outcomes of patients with chronic hepatitis B. In this review article, the immunopathogenesis of AF, and the involvement of innate and adaptive immune responses on the development of hepatitis B flare will be briefly reviewed, with the emphasis on the role of cytokines and chemokines.
Collapse
|
|
18
|
Gaspar R, Branco CC, Macedo G. Liver manifestations and complications in inflammatory bowel disease: A review. World J Hepatol 2021; 13:1956-1967. [PMID: 35070000 PMCID: PMC8727205 DOI: 10.4254/wjh.v13.i12.1956] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatobiliary manifestations are common in inflammatory bowel disease (IBD), with 30% of patients presenting abnormal liver tests and 5% developing chronic liver disease. They range from asymptomatic elevated liver tests to life-threatening disease and usually follow an independent course from IBD. The pathogenesis of liver manifestations or complications and IBD can be closely related by sharing a common auto-immune background (in primary sclerosing cholangitis, IgG4-related cholangitis, and autoimmune hepatitis), intestinal inflammation (in portal vein thrombosis and granulomatous hepatitis), metabolic impairment (in non-alcoholic fatty liver disease or cholelithiasis), or drug toxicity (in drug induced liver injury or hepatitis B virus infection reactivation). Their evaluation should prompt a full diagnostic workup to identify and readily treat all complications, improving management and outcome.
Collapse
Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Internal Medicine Department, Centro Hospitalar e Universitário do Porto, Porto 4200, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| |
Collapse
|
|
19
|
Daia MT, Median D, Buinoiu NF, Ciocarlan M, Iancu G, Panaitescu AM, Peltecu G, Streinu-Cercel A. COVID-19 Pandemic Impact on Cord Blood Collection for Stem Cell Use and Actual Perspectives. MÆDICA 2021; 16:189-193. [PMID: 34621337 DOI: 10.26574/maedica.2021.16.2.189] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective: The aim of the current study is to assess the prevalence of hepatitis B and the risk of hepatitis reactivation in carriers of hepatitis B virus (HBV) cancer patients who underwent chemotherapy for gynecologic and/or breast cancers in a single institution, during a period of five years, and to identify a relationship to some particular chemotherapy regimen, more prone to lead to reactivation. Material and methods: We conducted a retrospective chart review on all consecutive oncological patients treated for a gynecologic and/or breast cancers who presented for the first time to the Gynecologic Oncology Department of Filantropia Hospital, Bucharest, Romania, between January 2016 and December 2020. Results: A total of 1 895 patients diagnosed with ovarian, cervical, endometrial or breast cancers were admitted to hospital for systemic therapy during the mentioned period. Among these, only four patients (two patients with breast cancers, one cervical cancer and one endometrial carcinoma) were chronic carriers of HBV surface antigen (HBsAg positive). Patients received a variety of chemotherapeutic regimens including corticosteroids, gemcitabine, cisplatin, carboplatin, taxanes and anthracyclines. We report one reactivation that occurred in one occult carrier of hepatitis B virus diagnosed with breast cancer (HBsAg negative, hepatitis B core antibody positive - HBcAb), initially excluded from this study, as being screened negative for HBV, treated with taxanes-based chemotherapy and corticosteroids. Conclusion: HBV reactivation had a low incidence in our population of patients diagnosed with gynecologic or breast cancer who received systemic chemotherapy. The HBV reactivation risk was positively correlated with breast cancer and to taxanes-based regimens and glucocorticoids. Further studies to identify additional risk factors of HBV infection reactivation in gynecologic oncology patients and possible risk reducing measures are warranted.
Collapse
Affiliation(s)
| | | | | | | | - George Iancu
- Filantropia Clinical Hospital, Bucharest, Romania
| | | | | | | |
Collapse
|
|
20
|
Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, Piratvisuth T, Jia JD, Mizokami M, Cheng G, Chen GF, Liu ZW, Baatarkhuu O, Cheng AL, Ng WL, Lau P, Mok T, Chang JM, Hamid S, Dokmeci AK, Gani RA, Payawal DA, Chow P, Park JW, Strasser SI, Mohamed R, Win KM, Tawesak T, Sarin SK, Omata M. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int 2021; 15:1031-1048. [PMID: 34427860 PMCID: PMC8382940 DOI: 10.1007/s12072-021-10239-x] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. METHODS All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. RECOMMENDATIONS We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.
Collapse
Affiliation(s)
- George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China.
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.
| | - Ming-Lung Yu
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tz-You 1st Rd, Chinese Taipei, Kaohsiung, Taiwan.
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | | | - Hasmik Ghazinian
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Jin-Lin Hou
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Teerha Piratvisuth
- Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Ji-Dong Jia
- Liver Research Center, Beijing Friendship Hospital, Beijing, China
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Gregory Cheng
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
- Faculty of Health Science, Macau University, Macau SAR, China
| | - Guo-Feng Chen
- Department of Liver Diseases, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Zhen-Wen Liu
- Research Center for Liver Transplantation, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Oidov Baatarkhuu
- Department of Infectious Diseases, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ann Lii Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Woon Leung Ng
- Department of Medicine, United Christian Hospital, Hong Kong SAR, China
| | - Patrick Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - Tony Mok
- Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jer-Ming Chang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Saeed Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Rino A Gani
- Liver Transplantation Team, Ciptomangunkusumo Hospital, Jakarta, Indonesia
| | - Diana A Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Metro, Manila, Philippines
| | - Pierce Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Rosmawaiti Mohamed
- Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Khin Maung Win
- Yangon Gastroenterology and Liver Centre, Yangon, Myanmar
| | - Tanwandee Tawesak
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
|
21
|
Lee PC, Chao Y, Chen MH, Lan KH, Lee IC, Hou MC, Huang YH. Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma. J Immunother Cancer 2021; 8:jitc-2020-001072. [PMID: 32863270 PMCID: PMC7462159 DOI: 10.1136/jitc-2020-001072] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2020] [Indexed: 12/15/2022] Open
Abstract
Background Immunotherapy with immune checkpoint inhibitor (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC). However, whether ICIs would have the risk of hepatitis B virus (HBV) reactivation and the necessary of nucleos(t)ide analogs (NUCs) prophylaxis are still unclear. We aimed to investigate the role of NUCs prophylaxis in HBV-infected patients who underwent ICIs treatment. Methods The study was a retrospective prospective design to review and follow-up consecutive 62 patients with chronic hepatitis B or resolved HBV infection who had received ICIs treatment for the unresectable HCC. Of them, 60 patients with documented baseline serum HBV DNA value were classified into three categories according to the baseline HBV viral load and the status of antiviral therapy before ICI treatment. The clinical status, including tumor response, viral kinetics and liver function, was recorded and investigated. Results No HBV reactivation occurred in the 35 patients with HBV DNA ≤100 IU/mL on NUCs therapy. Of the 19 patients with HBV DNA >100 IU/mL who started NUCs simultaneously with ICI treatment, none encountered HBV reactivation during the immunotherapy. Of the six HBV patients without NUCs treatment, three had a greater than 1 log decrease in HBV viral load, and one maintained his serum HBV DNA in undetectable status during ICI treatment. Eventually, one out of six experienced HBV reactivation after 9 weeks of ICI treatment. Conclusion No patients on antiviral therapy developed HBV reactivation, and one out of six not receiving antiviral therapy had HBV reactivation. HBV viral load higher than 100 IU/mL is safe and not a contraindication for ICI treatment for HCC, if NUCs can be coadministrated.
Collapse
Affiliation(s)
- Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Huang Chen
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Keng-Hsin Lan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan .,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| |
Collapse
|
|
22
|
Han L, Zhou J, Zhou K, Zhu X, Zhao L, Fang B, Yin Q, Wei X, Zhou H, Li L, Xu B, Zhang J, Song Y, Gao Q. Safety and efficacy of CAR-T cell targeting BCMA in patients with multiple myeloma coinfected with chronic hepatitis B virus. J Immunother Cancer 2021; 8:jitc-2020-000927. [PMID: 32792360 PMCID: PMC7430488 DOI: 10.1136/jitc-2020-000927] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2020] [Indexed: 12/18/2022] Open
Abstract
Background Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in patients with chronic or resolved HBV infection undergoing anticancer therapy. There is a risk of HBV reactivation after infusion of chimeric antigen receptor (CAR) T cells for patients with refractory/relapsed (R/R) multiple myeloma (MM). Methods We administered B cell maturation antigen (BCMA) CAR-T cell by infusion to nine patients with R/R MM with chronic or resolved HBV infection. Patient serum was analyzed to determine the expression of five components of HBV and the copy number of HBV DNA. HBV reactivation was defined if a patient re-exhibited hepatitis B surface antigen (HBsAg) or HBV DNA regrowth after CAR-T therapy. Results In one patient who was HBsAg-positive, no HBV reactivation was observed during the follow-up period of 9.8 months after administration of anti-HBV drugs before and after CAR-T therapy. Among eight patients with MM who had resolved HBV infection, two patients administered prophylactic anti-HBV drugs did not exhibit HBV reactivation. Of the six patients who did not use prophylactic antiviral drugs, five did not exhibit HBV reactivation, while one showed recurrence of HBsAg without detection of HBV DNA or damage to liver function. The best objective response rate was 100%, and the progression-free survival (PFS) at 12 months was of 88.89% (median PFS was not observed). Conclusions These findings showed that BCMA CAR-T cell therapy could be used in patients with R/R MM with chronic or resolved HBV infection and that antiviral drugs should be administered in these patients during CAR-T cell therapy.
Collapse
Affiliation(s)
- Lu Han
- Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Jian Zhou
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Keshu Zhou
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Xinghu Zhu
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Lingdi Zhao
- Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Baijun Fang
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Qingsong Yin
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Xudong Wei
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Hu Zhou
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Linlin Li
- Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Bengling Xu
- Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Jishuai Zhang
- The Shenzhen Pregene Biopharma Company, Ltd, Shenzhen, China
| | - Yongping Song
- Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Quanli Gao
- Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| |
Collapse
|
|
23
|
Li P, Zhou L, Ye S, Zhang W, Wang J, Tang X, Liu J, Xu Y, Qian W, Liang A. Risk of HBV Reactivation in Patients With Resolved HBV Infection Receiving Anti-CD19 Chimeric Antigen Receptor T Cell Therapy Without Antiviral Prophylaxis. Front Immunol 2021; 12:638678. [PMID: 34335561 PMCID: PMC8320511 DOI: 10.3389/fimmu.2021.638678] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 06/29/2021] [Indexed: 01/31/2023] Open
Abstract
Background Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for hematologic malignancies and is predicted to experience widespread use in the near future. However, not all risks associated with this novel approach are well defined. There are few data in the risk of HBV reactivation and limited experience in management in patients with resolved HBV infection who undergo CAR-T cell therapy. Methods We performed a post-hoc analysis of a prospective clinical trial of anti-CD19 CAR-T (CART19) cell therapy in patients with relapsed or refractory (r/r) B-cell malignancies, and aimed at exploring the actual risk of HBV reactivation in a cohort of patients with resolved HBV infection receiving CART19 cell therapy in the absence of antiviral prophylaxis. Results In this study, we investigated the risk of HBV reactivation after CART19 cell therapy in 30 consecutive patients with B-cell malignancies and resolved HBV infection without antiviral prophylaxis, in the Tongji Hospital of Tongji University. In this cohort, two patients developed HBV reactivation 2 months and 14 months after CAR-T cell infusion, respectively, the latter of whom developed severe hepatitis. These findings showed that the incidence of HBV reactivation was 6.67% (95% CI, 0.8–22.1). Specifically, none of the 21 patients who were HBsAb positive (0.0%) versus two of nine patients who were HBsAb negative (22.2%) experienced HBV reactivation (p = 0.03), suggesting HbsAb seronegativity at baseline is a possible risk factor in this population. Although use of tocilizumab or corticosteroids has been associated with increased risk of HBV reactivation, none of the patients who received these agents had HBV reactivation in this study. Conclusion This is the first and largest study to assess the true incidence of HBV reactivation in patients with resolved HBV infection receiving CART19 cell therapy without antiviral prophylaxis. This study highlights that this population are at risk of developing HBV reactivation and indicates that close monitoring of HBV DNA is required in the absence of antiviral prophylaxis. In addition, antiviral prophylaxis is recommended in the HBsAb-negative subpopulation.
Collapse
Affiliation(s)
- Ping Li
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Lili Zhou
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Shiguang Ye
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Wenjun Zhang
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Junbang Wang
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Xiaochen Tang
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Jie Liu
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Yangyang Xu
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| | - Wenbin Qian
- Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Aibin Liang
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
| |
Collapse
|
|
24
|
Borojevic B, Chauhan A, Patterson S. Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma. BMJ Case Rep 2021; 14:14/7/e243526. [PMID: 34244190 DOI: 10.1136/bcr-2021-243526] [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] [Indexed: 12/12/2022] Open
Abstract
A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.
Collapse
Affiliation(s)
- Branko Borojevic
- General Medicine, Austin Health, Heidelberg, Victoria, Australia
| | - Ayushi Chauhan
- General Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - Scott Patterson
- Gastroenterology and General Medicine, Austin Health, Heidelberg, Victoria, Australia
| |
Collapse
|
|
25
|
Cao X, Wang Y, Li P, Huang W, Lu X, Lu H. HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies. Front Oncol 2021; 11:685706. [PMID: 34277431 PMCID: PMC8281013 DOI: 10.3389/fonc.2021.685706] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/16/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.
Collapse
Affiliation(s)
- Xing Cao
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yafei Wang
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Panyun Li
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Huang
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojuan Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongda Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
26
|
Management of Hepatitis B Virus Reactivation in Malignant Lymphoma Prior to Immunosuppressive Treatment. J Pers Med 2021; 11:jpm11040267. [PMID: 33918206 PMCID: PMC8066124 DOI: 10.3390/jpm11040267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/25/2022] Open
Abstract
Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.
Collapse
|
|
27
|
Udompap P, Kim WR. Hepatitis B Virus Reactivation and Management of Patients Undergoing Immunosuppression. HEPATITIS B VIRUS AND LIVER DISEASE 2021:427-454. [DOI: 10.1007/978-981-16-3615-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
28
|
Tseng TC, Liu CJ. Occult Hepatitis B Infection. HEPATITIS B VIRUS AND LIVER DISEASE 2021:411-425. [DOI: 10.1007/978-981-16-3615-8_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
29
|
Hepatitis B virus reactivation during temozolomide administration for malignant glioma. Int J Clin Oncol 2020; 26:305-315. [PMID: 33118116 DOI: 10.1007/s10147-020-01814-7] [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: 07/01/2020] [Accepted: 10/13/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. METHOD We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. RESULTS In one of two HBV carriers, HBV DNA turned positive 8 months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). CONCLUSION Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections.
Collapse
|
|
30
|
Abstract
Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.
Collapse
Affiliation(s)
- Yu Shi
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
| | - Min Zheng
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
| |
Collapse
|
|
31
|
Nasir M, Wu GY. Prevention of HBV Recurrence after Liver Transplant: A Review. J Clin Transl Hepatol 2020; 8:150-160. [PMID: 32832395 PMCID: PMC7438351 DOI: 10.14218/jcth.2020.00003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/16/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcinoma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglobulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst centers. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients.
Collapse
Affiliation(s)
- Myra Nasir
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| |
Collapse
|
|
32
|
Chen CH, Hsieh HH, Wu TY. Real-world prevalence of hepatitis B virus reactivation in cancer patients in Taiwan. J Oncol Pharm Pract 2020; 27:63-70. [PMID: 32264743 DOI: 10.1177/1078155220913095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis B virus carriers who receive systemic cancer chemotherapy have been found to be at a higher risk of hepatitis B virus reactivation. However, lack of standard prophylaxis protocol resulted in life-threatening adverse events. OBJECTIVE This retrospective study is to investigate prevalence and chemotherapy drug-induced hepatitis B virus reactivation in all types of cancer patients and establish an institutional clinical practice protocol.Methodology: This retrospective cohort study evaluated the incidence of hepatitis B virus infection, the pre-chemotherapy screening rate of hepatitis B surface antigen (HBsAg), and the severity of hepatitis B virus reactivation of cancer patients receiving intravenous chemotherapy between 2013 and 2014. Patients receiving local chemotherapy with intra-cavity instillation, drug- or alcohol-related hepatitis, or chemotherapy for immune diseases were excluded. RESULTS In total 784 patients, 404 patients (51.53%) underwent hepatitis B virus serum antigen (HBsAg) testing before chemotherapy, and 61 patients (7.78%) tested positive. Only 32 patients (4.08%) received prophylactic hepatitis B virus antiviral therapy. Patients receiving prophylactic antiviral drugs were significantly lower risk of hepatitis B virus reactivation than nonprophylaxis (relative risk, RR: 0.53, number needed to treat, NNT: 12). Moreover, our study found specific single or combined chemotherapy that may cause hepatitis B virus reactivation different from those of other studies conducted in Western countries. The differences may refer to enzymes, proteins and immune response of patients. CONCLUSIONS Our findings indicate that cancer patients receiving prophylactic antiviral drugs remain at risk of hepatitis B virus reactivation during chemotherapy. Therefore, the hepatitis B virus screen and chemotherapy control system was established in 2017 to reduce the risk of hepatitis B virus reactivation and improve patient safety.
Collapse
Affiliation(s)
- Chi-Hua Chen
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Hui-Hsia Hsieh
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Tien-Yuan Wu
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan
| |
Collapse
|
|
33
|
Niizuma K, Ogawa Y, Kogure T, Tominaga T. Case reports of latent HBV hepatitis in patients after neurosurgical treatment for hypothalamic and pituitary tumors. BMC Infect Dis 2020; 20:230. [PMID: 32188424 PMCID: PMC7081602 DOI: 10.1186/s12879-020-04971-2] [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] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 03/13/2020] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.
Collapse
Affiliation(s)
- Kuniyasu Niizuma
- Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi Japan
- Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi Japan
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi Japan
| | - Yoshikazu Ogawa
- Department of Neurosurgery, Kohnan Hospital, 4-20-1 Nagamachiminami, Taihaku-ku, Sendai, Miyagi 982-8523 Japan
| | - Takayuki Kogure
- Department of Gastroenterology and Hepatology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi Japan
| | - Teiji Tominaga
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi Japan
| |
Collapse
|
|
34
|
Koutsianas C, Thomas K, Vassilopoulos D. Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations. Ther Adv Musculoskelet Dis 2020; 12:1759720X20912646. [PMID: 32206094 PMCID: PMC7076579 DOI: 10.1177/1759720x20912646] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/11/2020] [Indexed: 12/14/2022] Open
Abstract
In patients with rheumatic diseases undergoing immunosuppressive treatment, hepatitis B virus reactivation (HBVr) has been long recognized as a major treatment-related adverse event with substantial morbidity and mortality. Because HBVr is easily preventable with appropriate screening and monitoring strategies, and, when indicated, prophylactic antiviral treatment, awareness of this complication is of the utmost importance, especially in the era of biologic treatments. As a condition, it continues to be topical, in view of the emergence of novel classes of immunosuppressive drugs (i.e. Janus kinase inhibitors) acquiring licenses for a variety of rheumatic diseases. The class-specific risk of these agents for HBVr has not yet been determined. Moreover, ambiguity still exists for the management of patients planned to be treated with traditional agents, such as cyclophosphamide and glucocorticoids, particularly in the setting of resolved HBV infection. Clinicians in the field of rheumatic diseases should be tailoring their practice according to the host's profile and treatment-specific risk for HBVr. In this review, the authors attempt to critically review the existing literature and provide practical advice on these issues.
Collapse
Affiliation(s)
- Christos Koutsianas
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, Athens, Greece
| | - Konstantinos Thomas
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, Athens, Greece
| | - Dimitrios Vassilopoulos
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass. Sophias Ave., Athens, 115 27, Greece
| |
Collapse
|
|
35
|
Li Z, Dong Y, Fan M, Yin Y, Zhu J, Li B, Huang W. Analysis of Hepatitis B Virus Reactivation After Radiotherapy in Patients With Hepatocellular Carcinoma Using the Lyman NTCP Model. Technol Cancer Res Treat 2020; 18:1533033819875136. [PMID: 31526114 PMCID: PMC6749789 DOI: 10.1177/1533033819875136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Purpose: To analyze the correlation of hepatitis B virus reactivation with patient-related and treatment-related dose–volume factors and to describe the feasibility of hepatitis B virus reactivation analyzed by a normal tissue complication probability model for patients with hepatocellular carcinoma treated with radiotherapy. Materials and Methods: Ninety patients with hepatitis B virus-related hepatocellular carcinoma treated with radiotherapy were enrolled in this retrospective study and were followed from June 2009 to December 2015. Of the 90 patients, 78 had received conventional fractionation radiotherapy to a mean dose of 39.6 to 50.4 Gy and 12 patients were scheduled to receive hypofractionation. The physical doses were converted into 2 Gy equivalents for analysis. The parameters, TD50 (1), n, and m, of the Lyman-Kutcher-Burman normal tissue complication probability model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to against model overfitting and improve the model stability. Results: Radiation-induced liver diseases were 17.8%, hepatitis B virus reactivation was 22.2%, and hepatitis B virus reactivation-induced hepatitis was 21.1%, respectively. In multivariate analysis, the V5Gy was associated with hepatitis B virus reactivation; TD50 (1), m, and n were 32.3, 0.55, and 0.71 Gy, respectively, for hepatitis B virus reactivation. Bootstrap and leave-one-out results showed that the hepatitis B virus parameter fits were extremely robust. Conclusion: A Lyman-Kutcher-Burman normal tissue complication probability model has been established to predict hepatitis B virus reactivation for patients with hepatocellular carcinoma who received radiotherapy.
Collapse
Affiliation(s)
- Zhenjiang Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yinping Dong
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.,School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Min Fan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yong Yin
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jian Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| |
Collapse
|
|
36
|
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.
Collapse
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.
| |
Collapse
|
|
37
|
Thioacetamide-induced liver damage and thrombocytopenia is associated with induction of antiplatelet autoantibody in mice. Sci Rep 2019; 9:17497. [PMID: 31767905 PMCID: PMC6877565 DOI: 10.1038/s41598-019-53977-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 10/30/2019] [Indexed: 02/06/2023] Open
Abstract
Thrombocytopenia is usually associated with liver injury, elevated plasma aspartate aminotransferase and alanine aminotransferase levels, and high antiplatelet immunoglobulin (Ig) titers, although the mechanism behind these effects remains elusive. Deciphering the mechanism behind acute liver disease–associated thrombocytopenia may help solve difficulties in routine patient care, such as liver biopsy, antiviral therapy, and surgery. To determine whether liver damage is sufficient per se to elicit thrombocytopenia, thioacetamide (TAA)-induced hepatitis rodent models were employed. The analysis results indicated that TAA treatment transiently induced an elevation of antiplatelet antibody titer in both rats and mice. B-cell-deficient (BCD) mice, which have loss of antibody expression, exhibited markedly less thrombocytopenia and liver damage than wild-type controls. Because TAA still induces liver damage in BCD mice, this suggests that antiplatelet Ig is one of the pathogenic factors, which play exacerbating role in the acute phase of TAA-induced hepatitis. TNF-α was differentially regulated in wild-type versus BCD mice during TAA treatment, and anti-TNF treatment drastically ameliorated antiplatelet Ig induction, thrombocytopenia, and liver injury, suggesting that the TNF pathway plays a critical role in the disease progression.
Collapse
|
|
38
|
Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma. Cancers (Basel) 2019; 11:cancers11111819. [PMID: 31752356 PMCID: PMC6895787 DOI: 10.3390/cancers11111819] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 11/16/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022] Open
Abstract
Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of fulminant hepatitis. The preventive strategy for HBV reactivation in patients with malignant lymphoma has already been established based on some prospective studies. As there was an increased number of novel agents being approved for the treatment of multiple myeloma (MM), the number of reported cases of HBV reactivation among MM patients has gradually increased. We conducted a Japanese nationwide retrospective study and revealed that HBV reactivation in MM patients is not rare and that autologous stem cell transplantation is a significant risk factor. In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required.
Collapse
|
|
39
|
Ataca Atilla P, Yalçıner M, Atilla E, İdilman R, Beksaç M. Hepatitis B Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Regimens Containing Lenalidomide and/or Bortezomib. Turk J Haematol 2019; 36:266-273. [PMID: 31368290 PMCID: PMC6863023 DOI: 10.4274/tjh.galenos.2019.2019.0103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective: Reactivation of the hepatitis B virus (HBV) refers to an increase in HBV replication in a patient with inactive or resolved HBV. In this retrospective study, our aim is to present and compare HBV reactivation in multiple myeloma (MM) patients who received lenalidomide and/or bortezomib at any time during treatment, evaluate the factors associated with reactivation, and demonstrate the outcome of patients. Materials and Methods: We evaluated 178 MM patients who received lenalidomide (n=102) and/or bortezomib (n=174) during their treatment schedules. The HBsAg, anti-HBc, anti-HBs, HBeAg, and anti-HBe were detected by chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers were determined by quantitative PCR. The results were evaluated by IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). Results: HBV reactivation was diagnosed in 6 patients (3%) after bortezomib and in 8 patients (8%) after bortezomib and lenalidomide. Three of the patients in each group had HBsAg+, HBeAg+, AntiHBeAg-, AntiHBc-, and AntiHBS+ status, whereas 5 patients in the bortezomib- and lenalidomide-treated group and 3 patients in the bortezomib-treated group had HBsAg-, HBeAg-, AntiHBeAg-, AntiHBc-, and AntiHBS+ status prior to treatment. There were no statistical differences observed between HBV reactivation in the bortezomib-treated or bortezomib- and lenalidomide-treated groups in terms of age at diagnosis, sex, International Staging System subtype, frequency of extramedullary disease, dialysis requirement, or receiving of autologous stem cell transplantation. In patients who received antiviral prophylaxis, a higher incidence of HBV reactivation was detected in HBsAg-positive patients compared to HBsAg-negative patients (4/4, 100% vs. 2/7, 29%; p=0.045). The 3-year and 5-year overall survival rates were similar in patients with or without HBV reactivation (83% vs. 84%, 73% vs. 74%, p=0.84). Conclusion: Close follow-up is recommended for not only HBsAg-positive but also HBsAg-negative patients.
Collapse
Affiliation(s)
- Pınar Ataca Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Merih Yalçıner
- Ankara University Faculty of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Erden Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Ramazan İdilman
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Meral Beksaç
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| |
Collapse
|
|
40
|
Sasadeusz J, Grigg A, Hughes PD, Lim SL, 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: Patients with Hematological and Solid Tumor Malignancies. Clin Liver Dis 2019; 23:511-519. [PMID: 31266624 DOI: 10.1016/j.cld.2019.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Patients with malignancies require chemotherapy and other immunosuppressive therapies for treatment. Because of this immunosuppression, in patients who have ever been exposed to hepatitis B it is possible for reactivation to occur. This reactivation can be fatal. Reactivation is particularly likely in patients who receive B cell-active agents such as rituximab. The occurrence of reactivation flares may also delay further chemotherapy, which can negatively affect the outcome of the underlying malignancy. Accordingly, it is important to screen patients for markers of hepatitis B and institute antiviral prophylaxis to prevent reactivation.
Collapse
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, North 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
| |
Collapse
|
|
41
|
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: Other Populations and Newer Agents. Clin Liver Dis 2019; 23:521-534. [PMID: 31266625 DOI: 10.1016/j.cld.2019.04.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.
Collapse
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, North 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
| |
Collapse
|
|
42
|
Sagnelli C, Pisaturo M, Calò F, Martini S, Sagnelli E, Coppola N. Reactivation of hepatitis B virus infection in patients with hemo-lymphoproliferative diseases, and its prevention. World J Gastroenterol 2019; 25:3299-3312. [PMID: 31341357 PMCID: PMC6639550 DOI: 10.3748/wjg.v25.i26.3299] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/10/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.
Collapse
Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Salvatore Martini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| |
Collapse
|
|
43
|
KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
|
|
44
|
Wang B, Mufti G, Agarwal K. Reactivation of hepatitis B virus infection in patients with hematologic disorders. Haematologica 2019; 104:435-443. [PMID: 30733266 PMCID: PMC6395346 DOI: 10.3324/haematol.2018.210252] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 01/18/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in patients with past or chronic HBV infection, usually occurring in the context of immunosuppression. HBV reactivation has been most commonly reported in patients with hematologic disorders, with potentially serious and life-threatening consequences. In this review, we discuss the basis and presentation of HBV reactivation, and risk factors in terms of the host, the virus and the immunosuppression regimen, including newer agents used to manage hematologic malignancies. We overview the management of HBV reactivation, highlighting an up-dated recommendation on the use of newer nucleoside and nucleotide analogs, such as tenofovir and entecavir, for antiviral prophylaxis.
Collapse
Affiliation(s)
| | - Ghulam Mufti
- Department of Hematology, King's College Hospital, London, UK
| | | |
Collapse
|
|
45
|
Chen X, Hu Y, Zhang W, Chen K, Hu J, Li X, Liang L, Cai X, Hu J, Wang K, Huang A, Tang N. Cisplatin induces autophagy to enhance hepatitis B virus replication via activation of ROS/JNK and inhibition of the Akt/mTOR pathway. Free Radic Biol Med 2019; 131:225-236. [PMID: 30550853 DOI: 10.1016/j.freeradbiomed.2018.12.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 12/06/2018] [Accepted: 12/10/2018] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B virus (HBV) infection remains a serious global health concern. Cisplatin is a chemotherapeutic agent commonly used to treat various cancers. However, HBV-infected patients receiving chemotherapy are at risk of HBV reactivation via unknown mechanisms, which we aimed to elucidate in this study. We found that autophagy plays a central role in cisplatin-induced HBV replication. Cisplatin treatment induced autophagy in both HBV-replicating cells and an HBV-transgenic mouse model as evident from marked upregulation of microtubule-associated protein 1 light chain 3 (LC3)-II and the accumulation of red fluorescent protein (RFP)-LC3 puncta. Cisplatin induced complete autophagic flux, which was detected via monitoring of p62 degradation and RFP-GFP-LC3 expression. Inhibition of autophagy by chloroquine, 3-methyladenine, or Atg5 knockdown significantly attenuated cisplatin-induced HBV replication. Additionally, cisplatin-induced autophagy could be significantly attenuated by using the ROS scavenger N-acetyl-l-cysteine. Mechanically, cisplatin promoted HBV replication and autophagy through ROS/JNK and AKT/mTOR signaling. Inhibition of JNK or activation of Akt/mTOR signaling reversed cisplatin-mediated autophagy and HBV replication promotion. In contrast, suppression of Akt/mTOR signaling further promoted cisplatin-induced HBV replication. Finally, pharmacotherapeutic inhibition of autophagy or ROS production impaired HBV production induced by cisplatin in vivo. Together, our results indicate that ROS/JNK and mTOR/AKT-mediated autophagy plays an important role in cisplatin-induced HBV reactivation.
Collapse
Affiliation(s)
- Xuemei Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yuan Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Wenlu Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ke Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaosong Li
- The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Li Liang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xuefei Cai
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jieli Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Kai Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
| | - Ailong Huang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
| | - Ni Tang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
| |
Collapse
|
|
46
|
Morillas RM, López Sisamón D. Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla. Med Clin (Barc) 2019; 152:107-114. [DOI: 10.1016/j.medcli.2018.08.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 08/30/2018] [Accepted: 08/31/2018] [Indexed: 02/07/2023]
|
|
47
|
Wong GLH, Yuen BWY, Chan HLY, Tse YK, Yip TCF, Lam KLY, Lui GCY, Wong VWS. Impact of dose and duration of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B. Liver Int 2019; 39:271-279. [PMID: 30179316 DOI: 10.1111/liv.13953] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 08/06/2018] [Accepted: 08/28/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Systemic corticosteroid is used for different medical conditions and may cause hepatitis B virus (HBV) reactivation. AIMS To study the impact of duration and peak dose of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B (CHB). METHODS All patients who received corticosteroid from January 2001 to December 2004 were retrieved from the Hospital Authority, Hong Kong. We stratified patients by daily dose prednisolone equivalents (<20 mg, 20-40 mg, >40 mg) and durations (<7; 7-28; >28 days). The primary endpoint was hepatitis flare (alanine aminotransferase >2×upper limit of normal, ie 80 IU/L) at 1 year. RESULTS A total of 85 763 patients fulfilled the inclusion criteria (5254 CHB, 80 509 non-CHB). CHB patients had higher risk of hepatitis flare (388/5254 [7.8%]) than those without CHB (2728/80 509 [4.2%]; P < 0.001 by log-rank test). Among CHB patients, peak daily dose >40 mg compared to <20 mg prednisolone equivalents (adjusted hazard ratio [aHR] 1.64, 95% CI 1.26-2.14; P < 0.001) was an independent risk factor of hepatitis flare. Risk of hepatitis flare started to increase in those receiving corticosteroid of peak daily dose >40 mg prednisolone equivalents even for <7 days (aHR 1.55, P = 0.026), which was also increased for 7-28 days and >28 days (aHR 1.90 and 1.64 respectively, both P < 0.001). CONCLUSION Even short courses of high-dose corticosteroid increase the risk of hepatitis flare in CHB patients. Patients receiving high-dose corticosteroid should be considered for antiviral prophylaxis regardless of the duration of treatment.
Collapse
Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Becky Wing-Yan Yuen
- Department of Statistics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Kelvin Long-Yan Lam
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Chung-Yan Lui
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| |
Collapse
|
|
48
|
Molagic V, Mihailescu R, Tiliscan C, Popescu C, Vladareanu AM, Catana R, Radulescu M, Arama V, Arama SS. Hepatitis B and C Virus Reactivation Patterns in a Romanian Cohort of Patients with Chronic Lymphoproliferative Disorders. Indian J Hematol Blood Transfus 2019; 35:459-464. [PMID: 31388257 DOI: 10.1007/s12288-018-01063-9] [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: 03/27/2018] [Accepted: 12/13/2018] [Indexed: 10/27/2022] Open
Abstract
Hepatitis B and C virus (HBV and HCV) reactivations have become more common following the intensive use of biological therapies for the treatment of chronic lymphoproliferative disorders (CLD). We evaluate risk factors for virus reactivation and exitus in patients diagnosed with CLD and HBV or HCV infection, undergoing rituximab-chemotherapy (R-chemo). A prospective, observational study in two tertiary-care Romanian hospitals, between December 2007 and May 2010, of patients diagnosed with CLD undergoing R-chemo. HBV and HCV serological markers, viral load, fibrosis and necroinflammation were assessed at baseline and every 3-6 months. We screened 502 patients diagnosed with CLDs (77.2% non-Hodgkin lymphomas) and enrolled 57 patients with HBV and/or HCV infection with a mean age of 61.35 ± 11.1 years. The replicative virus was HBV in 23 patients (40.3%), HCV in 33 patients (57.9%). HCV reactivation rate (15.6%) was lower than for HBV (45.5%) (p = 0.02). In univariate analysis, viral reactivation was associated with aggressive CLD (p = 0.01), HBV (p = 0.01) and lymphopenia (p = 0.02). Death was associated with aggressive CLD (p = 0.01), viral reactivation (p = 0.001) and high baseline viremia (p = 0.05). In multivariate analysis, viral reactivation was associated with lymphopenia (OR 0.05, 95% CI 0.003-0.85, p = 0.03). Risk of death was 10 times higher for patients with viral reactivation (95% CI 1.54-65.5, p = 0.01). A quarter of the infected patients were diagnosed with viral reactivation. While hepatitis C was more prevalent than hepatitis B in patients with CLD, viral reactivation was found 3 times more frequently in patients with hepatitis B than C.
Collapse
Affiliation(s)
- Violeta Molagic
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania
| | - Raluca Mihailescu
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania
| | - Catalin Tiliscan
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania.,2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
| | - Cristina Popescu
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania.,2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
| | - Ana Maria Vladareanu
- 2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania.,3Department of Hematology, University Emergency Hospital Bucharest, 169 Splaiul Independentei Street, 050098 Bucharest, Romania
| | - Remulus Catana
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania
| | - Mihaela Radulescu
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania.,2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
| | - Victoria Arama
- 1National Institute for Infectious Diseases "Prof. Dr. Matei Balş", 1st Grozovici Street, 021105 Bucharest, Romania.,2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
| | - Stefan Sorin Arama
- 2Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Street, 050474 Bucharest, Romania
| |
Collapse
|
|
49
|
Chien RN, Kao JH, Peng CY, Chen CH, Liu CJ, Huang YH, Hu TH, Yang HI, Lu SN, Ni YH, Chuang WL, Lee CM, Wu JC, Chen PJ, Liaw YF. Taiwan consensus statement on the management of chronic hepatitis B. J Formos Med Assoc 2018; 118:7-38. [PMID: 30527436 DOI: 10.1016/j.jfma.2018.11.008] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 11/06/2018] [Accepted: 11/15/2018] [Indexed: 01/10/2023] Open
Abstract
The experts of Taiwan Association for the Study of Liver (TASL) have actively participated and led the guidelines on hepatitis B virus (HBV) management by Asian Pacific Association for the Study of Liver (APASL) which is the first international association for the study of liver to publish the statement on HBV management before. However, there are more and more new data on the natural history and treatment of HBV infection in the past decade. These include new application of an old biomarker (quantitative HBsAg), clinical significance of HBV genotype and naturally occurring mutations, the role of non-invasive examination in evaluating severity of hepatic fibrosis, clinical significance of outcome calculators, new drug or new combination strategies towards more effective therapy and organ transplantation including liver and non-liver transplantation. It is time to publish the guidelines on HBV management of Taiwan. Hence, TASL have conducted an expert meeting to review, to discuss and to debate the relevant literatures, followed by draft the manuscript of HBV management guidelines and recommendations. The guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patient receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
Collapse
Affiliation(s)
- Rong-Nan Chien
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan.
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hwa-I Yang
- Department of Genomic Research Center, Sinica Academia, Taipei, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
| | - Won-Long Chuang
- Division of Hepatobiliary and Pancreas, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jaw-Chin Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Linkou Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan
| |
Collapse
|
|
50
|
Su J, Long L, Zou K. Antiviral prophylaxis for preventing reactivation of hepatitis B virus in rheumatic patients: a systematic review and meta-analysis. Clin Rheumatol 2018; 37:3201-3214. [PMID: 29637482 DOI: 10.1007/s10067-018-4096-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 02/26/2018] [Accepted: 04/02/2018] [Indexed: 02/06/2023]
Abstract
To estimate the risk of reactivation of hepatitis B virus (HBV) and evaluate the effectiveness of antiviral prophylaxis (AVP) in patients with different status of HBV infection undergoing antirheumatic therapies. We searched Cochrane Library, Medline, and EMBASE for randomized controlled trials (RCTs), quasi-RCTs, non-RCTs, cohort studies, or case series studies examining reactivation of HBV in patients undergoing antirheumatic therapy with or without AVP. We estimated the HBV reactivation rate (HRR) and its 95% confidence interval (CI) among different patient groups (indirect comparison). We also calculated rate ratio (RR), rate difference (RD) with their 95% CIs, and the number needed to treat (NNT) of AVP (direct comparison). Fifty-three case series studies with 2162 patients were included. The RD of AVP was - 0.13 (95% CI - 0.21 to - 0.05) for all patients, - 0.16 (95% CI - 0.26 to - 0.06) for rheumatic patients with chronic HBV infection, but not statistically significant for patients with other status of HBV infection. Lamivudine (RD - 0.10, 95% CI - 0.25 to 0.05) was less effective than other prophylactic antiviral drugs (RD - 0.31, 95% CI - 0.52 to - 0.11). The HHR varied from 55 to 5% by HBV status and treatment. There is limited evidence that AVP was effective for preventing reactivation of HBV in patients undergoing antirheumatic therapy. The effectiveness varies by patient HBV status and antiviral regimens. Rheumatic HBV carriers may be more beneficial from AVP, and lamivudine may be inferior to other AVP regimens. Findings in this study warrant further investigation in rigorous RCTs.
Collapse
Affiliation(s)
- Jiang Su
- Department of Rheumatology and Immunology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of the University of Electronic Science and Technology, Chengdu, China
| | - Li Long
- Department of Rheumatology and Immunology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of the University of Electronic Science and Technology, Chengdu, China
| | - Kun Zou
- Department of Medical Records and Statistics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of the University of Electronic Science and Technology, No. 32, West Second Section, First Ring Road, Chengdu, China.
| |
Collapse
|