|
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
|
Marty C, Adam JP, Martel-Laferrière V, Doucet S, Martel D. Impact of universal hepatitis B virus (HBV) screening using chemotherapy orders on the HBV reactivation in cancer patients. Support Care Cancer 2024; 32:541. [PMID: 39046551 DOI: 10.1007/s00520-024-08750-6] [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: 01/29/2024] [Accepted: 07/18/2024] [Indexed: 07/25/2024]
Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. METHODS This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). RESULTS On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. CONCLUSION Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements.
Collapse
Affiliation(s)
- Céline Marty
- Faculty of Pharmacy, Aix-Marseille Université, Marseille, France
| | - Jean-Philippe Adam
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada.
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada.
| | - Valérie Martel-Laferrière
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Microbiology and Infectious Diseases, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montréal, QC, Canada
| | - Stéphane Doucet
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Medicine-Medical Oncology/Hematology, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
| | - Dominic Martel
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
| |
Collapse
|
|
3
|
Cohen EB, Regev A, Garg A, Di Bisceglie AM, Lewis JH, Vierling JM, Hey-Hadavi J, Steplewski K, Fettiplace A, Chen CL, Pehlivanov N, Kendrick S, I Avigan M. Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy. Drug Saf 2024; 47:321-332. [PMID: 38353882 PMCID: PMC10954982 DOI: 10.1007/s40264-024-01399-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2024] [Indexed: 03/21/2024]
Abstract
Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker-positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.
Collapse
Affiliation(s)
- Eric B Cohen
- AbbVie Inc., Pharmacovigilance and Patient Safety, North Chicago, IL, USA.
| | - Arie Regev
- Eli Lilly and Company, Global Patient Safety, Indianapolis, IN, USA
| | - Anju Garg
- Sanofi, Patient Safety & Pharmacovigilance, Bridgewater, NJ, USA
| | | | - James H Lewis
- Division of Gastroenterology, Georgetown University, Washington, DC, USA
| | - John M Vierling
- Section of Gastroenterology and Hepatology and Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA
| | | | - Klaudia Steplewski
- GlaxoSmithKline LLC, Clinical Safety and Pharmacovigilance, Collegeville, PA, USA
| | | | - Chunlin L Chen
- Bayer HealthCare Pharmaceuticals, LLC. Pharmacovigilance, Berlin, Germany
| | - Nonko Pehlivanov
- Merck & Co., INC, Clinical Safety Risk Management, Rahway, NJ, USA
| | - Stuart Kendrick
- GlaxoSmithKline LLC, Medical Affairs-Hepatology, Stevenage, UK
| | - Mark I Avigan
- Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA
| |
Collapse
|
|
4
|
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
|
|
5
|
Yi JH, Lee JL, Lee YJ, Kang HJ, Park YH, Yuh YJ, Lim SN, Kim HJ, Jung SH, Lee JJ, Cho HJ, Moon JH, Yhim HY, Kim K. Outcome of Multiple Myeloma Patients With Hepatitis B Surface Antigen: Korean Multiple Myeloma Working Party 2103 Study. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:e50-e57.e2. [PMID: 37973459 DOI: 10.1016/j.clml.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/06/2023] [Accepted: 10/11/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.
Collapse
Affiliation(s)
- Jun Ho Yi
- Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, Korea
| | - Jung Lim Lee
- Department of Hemato-oncology, Daegu Fatima Hospital, Daegu, Korea
| | - Yoo Jin Lee
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Hye Jin Kang
- Division of Hematology/Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Young Hoon Park
- Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Jin Yuh
- Department of Internal Medicine, Sanggye-Paik Hospital, Inje University, Seoul, Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Sung-Hoon Jung
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Je-Jung Lee
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Hee Jeong Cho
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Joon Ho Moon
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
| | - Kihyun Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| |
Collapse
|
|
6
|
Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
| |
Collapse
|
|
7
|
Dezan MGF, Cavalcante LN, Cotrim HP, Lyra AC. Hepatobiliary disease after bone marrow transplant. Expert Rev Gastroenterol Hepatol 2023; 17:129-143. [PMID: 36655915 DOI: 10.1080/17474124.2023.2169671] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/13/2023] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.
Collapse
Affiliation(s)
- Maria Gabriela Fernandes Dezan
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Lourianne Nascimento Cavalcante
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Helma Pinchemel Cotrim
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Andre Castro Lyra
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| |
Collapse
|
|
8
|
Zhao Y, Song Y, Zhang H, Qu T, Axinbai M, Yang Y, Zhang L. Efficacy of nucleos(t)ide analogues(NAs) in preventing virus reactivation in oncology patients with HBV infection after chemotherapy or surgery: A network meta-analysis. Front Oncol 2023; 12:1050714. [PMID: 36727050 PMCID: PMC9885183 DOI: 10.3389/fonc.2022.1050714] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023] Open
Abstract
Objective In this study, we aimed to perform a network meta-analysis to compare the effectiveness of NAs in decreasing the reactivation of HBV, reducing chemotherapy disruption, and improving survival in oncology patients. Methods Relevant randomized controlled trials (RCT) evaluating the impact of NAs in HBV infected-related oncology patients were retrieved from electronic databases. The outcome indicators included reactivation rate, survival rate of 1 to 3 years after treatment, and chemotherapy disruption rate. The studies were evaluated for bias using the RCT risk of bias assessment tool recommended in the Cochrane Handbook. The risk ratio (RR) was used to compare the outcome indicators for the anti-viral treatment, and the surface under the cumulative ranking curves (SUCRA) was used to identify the optimal therapeutic regime. Results A total of 67 trials containing 5722 patients were included in this study. Regarding the reduction of reactivation rate, entecavir, lamivudine, adefovir alone were less effective than the combination of lamivudine and entecavir (94.9%), with RR values ranging from 3.16 to 3.73. However, based on SUCRA, the efficacy of telbivudine (80.3%) and the combination of lamivudine and adefovir dipivoxil (58.8%) were also acceptable. Entecavir (RR values ranging from 1.25 to 1.50) and lamivudine (RR values ranging from 1.27 to 1.35) can prolong the survival rate of patients at 1-3 years, and were better than adefovir dipivoxil in the comparison of 1-year survival rate. The RR values were 1.18 and 1.19, respectively. And entecavir 's ranking in SUCRA was more stable. Entecavir, lamivudine, and tenofovir all reduced chemotherapy interruption rates compared with no antiviral therapy, especially for tenofovir. Conclusions Current evidence shows that lamivudine combined with entecavir, telbivudine, and lamivudine combined with adefovir dipivoxil were the most effective in preventing virus reactivation in HBV infected-related cancer patients treated with chemotherapy. Entecavir had the most stable effect on survival, while tenofovir had the best impact on reducing the chemotherapy disruption rate. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions. Systematic review registration PROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD4202250685.
Collapse
Affiliation(s)
- Yuqing Zhao
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yingying Song
- Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Huan Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Tongshuo Qu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Malina Axinbai
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yidian Yang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Liping Zhang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China,Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China,*Correspondence: Liping Zhang,
| |
Collapse
|
|
9
|
2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
10
|
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
11
|
El Jamaly H, Eslick GD, Weltman M. Meta-analysis: hepatitis B reactivation in patients receiving biological therapy. Aliment Pharmacol Ther 2022; 56:1104-1118. [PMID: 35975904 DOI: 10.1111/apt.17155] [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: 03/21/2022] [Revised: 04/12/2022] [Accepted: 07/11/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers. AIM To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab METHOD: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)). RESULTS We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0-35.9, n = 5), 16.6% (95% CI: 9.5-27.5%, n = 6), 40.5% (95% CI: 20.3-64.5%, n = 4) and 19.1% (95% CI: 7.3-41.2%, n = 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8-8.7%, number of studies: n = 18), 2.6% (95% CI: 1.4-4.7%, n = 18), 4.4% (95% CI: 2.2-8.7%, n = 12) and 6.4% (95% CI: 2.2-16.8, n = 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis. CONCLUSIONS HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high-risk groups was low, contrary to clinical practice guidelines.
Collapse
Affiliation(s)
- Hydar El Jamaly
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, New South Wales, Australia
- Nepean Clinical School, The University of Sydney, Penrith, New South Wales, Australia
| | - Guy D Eslick
- The NHMRC Centre for Research Excellence for Digestive Health, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, New South Wales, Australia
- Nepean Clinical School, The University of Sydney, Penrith, New South Wales, Australia
| |
Collapse
|
|
12
|
Papatheodoridi M, Tampaki M, Lok AS, Papatheodoridis GV. Risk of HBV reactivation during therapies for HCC: A systematic review. Hepatology 2022; 75:1257-1274. [PMID: 34918361 DOI: 10.1002/hep.32241] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Treatment for HCC has evolved rapidly, but the risk of HBV reactivation to new therapies is unclear. We systematically reviewed data on HBV reactivation in patients receiving HCC therapy in relation to use of HBV antiviral prophylaxis. APPROACH AND RESULTS A literature search was performed to identify all published studies including HBsAg-positive patients with HCC providing data on HBV reactivation. Forty-one studies with 10,223 patients, all from Asia, were included. The pooled HBV reactivation rate was 5% in patients receiving no specific HCC therapy and was higher in patients undergoing surgical resection (16%), transarterial chemoembolization (19%), or radiotherapy (14%) and intermediate in patients treated with local ablation therapy (7%) or systemic agents (7%). HBV reactivation rates were higher in those without compared to those with HBV prophylaxis (ablation, 9% versus 0%; resection, 20% versus 3%; chemoembolization, 23% versus 1%; external radiotherapy alone, 18% versus 0%; systemic therapy, 9% versus 3%). HBV-related biochemical reactivation rates varied between 6%-11% and 2% in patients receiving HCC therapies with high and intermediate HBV reactivation risk, respectively. Liver decompensation and death were rarely reported (0%-3%) and only in patients receiving HCC treatment with high HBV reactivation risk. CONCLUSIONS HBsAg-positive patients with HCC are at high or intermediate risk of HBV reactivation depending on the type of HCC therapy. Nucleos(t)ide analogue prophylaxis reduces the risk of HBV reactivation, practically eliminates the risk of hepatitis flare, and should be administered regardless of HCC treatment.
Collapse
Affiliation(s)
| | - Maria Tampaki
- Department of Gastroenterology and Liver Transplantation UnitMedical School of National and Kapodistrian University of AthensGeneral Hospital of Athens "Laiko"AthensGreece
| | - Anna S Lok
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMichiganUSA
| | - George V Papatheodoridis
- Department of Gastroenterology and Liver Transplantation UnitMedical School of National and Kapodistrian University of AthensGeneral Hospital of Athens "Laiko"AthensGreece
| |
Collapse
|
|
13
|
The Korean Association for the Study of the Liver (KASL). 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: 69] [Impact Index Per Article: 23.0] [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
|
|
14
|
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
|
|
15
|
Abstract
Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.
Collapse
Affiliation(s)
- Wei Huang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| |
Collapse
|
|
16
|
Jin M, Chen Y, Hu S, Zhu M, Wang Y, Chen M, Peng Z. Association of Virological Response to Antiviral Therapy With Survival in Intermediate-Stage Hepatitis B Virus-Related Hepatocellular Carcinoma After Chemoembolization. Front Oncol 2021; 11:751777. [PMID: 34745980 PMCID: PMC8569860 DOI: 10.3389/fonc.2021.751777] [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: 08/02/2021] [Accepted: 10/11/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction Role of response to antiviral therapies on survival of patients with intermediate-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) undergoing transarterial chemoembolization (TACE) remains unknown. We aimed to determine whether virological response (VR) or prolonged maintained virological response (MVR) to nucelos(t)ide analogues (NA) therapy could result in improved survival in HBV-HCC patients receiving TACE. Methods Between January 2012 and October 2018, data of patients with intermediate HBV-HCC who underwent TACE and started NA therapy within one week prior to TACE treatment at our institution were reviewed. Overall survival (OS) was compared using the Kaplan-Meier method with log-rank test between different VR status groups. Univariable and multivariable Cox regression analyses were used to determine the association between achievement of VR or MVR and OS. VR was defined as an undetectable HBV DNA level (<100 IU/ml) on two consecutive measurements during NA treatment. MVR was defined as a persistently undetectable HBV DNA level after achieving a VR. Results A total of 1265 patients undergoing TACE with a median follow-up time of 18 months (range, 2-78 months) were included in the analysis. Of 1265 NA-treated patients [1123 (88.8%) male, median (range) age, 56 (18-75) years], 744 patients (58.8%) achieved VR and the remaining patients (41.2%) did not. Patients with achievement of VR showed a significantly longer OS than those without VR (median OS: 21 vs 16 months; HR, 0.707; 95% CI, 0.622-0.804; P<0.001). Among patients with VR, MVR was present in 542 patients (72.8%), while the other 202 patients (27.2%) in the non-MVR group. The OS for the MVR group was significantly higher than the non-MVR group (median OS: 23.2 vs 18 months; HR, 0.736; 95% CI, 0.612-0.885; P=0.001). Additionally, patients with MVR status more than two years showed a better OS than those with just one-year (HR, 0.719; 95% CI, 0.650-0.797; P<0.001) or one-to-two-year MVR (HR, 0.612; 95% CI, 0.471-0.795; P=0.024). On multivariable analyses, splenomegaly and up-to-seven criteria were independent prognostic factors of OS in both VR and MVR cohorts. Conclusions In patients with intermediate-stage HBV-HCC, both VR to antiviral therapy and prolonged response are associated with prolonged OS after TACE, especially for those within up-to-seven criteria.
Collapse
Affiliation(s)
- Meng Jin
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yong Chen
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuifang Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Meiyan Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yan Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
17
|
Wang K, Xia Y, Zhu Y, Yu W, Guo Y, Liu L. Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study. J Immunother Cancer 2021. [PMCID: PMC8578995 DOI: 10.1136/jitc-2021-003195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data demonstrating the impact of ICIs on HBV DNA level in HBV-HCC patients undergoing nucleos(t)ide analog (NA) therapy and of HBV DNA variation on patient survival. In this study, we aimed to investigate this issue in the real world. Methods In this single-center retrospective study, we reviewed 182 baseline hepatitis B surface antigen (HBsAg)-positive HBV-HCC patients who were treated with ICIs and pre-emptive NAs. The demographic characteristics, tumor status, treatments, HBV DNA, HBsAg, liver function, antitumor response, and patient survival were investigated. The primary endpoints were the virological breakthrough (VB) rate, HBV reactivation (HBVr) rate, and long-term HBV DNA control; the secondary endpoints were the overall survival (OS) and progression-free survival (PFS). Results (1) VB and HBVr occurred in 18.1% (33/182) and 4.4% (8/182) of patients with a median occurrence time of 3.9 months (range, 0.7–16.0) and 8.0 months (range, 3.0–16.0), respectively. The HBV DNA negative rates were 26.1% and 0 at 24 and 48 weeks in the VB group and 12.5% and 0 in the HBVr group, respectively. A baseline HBsAg level ≥200 IU/mL was the only risk factor for VB (OR 9.9, 95% CI 2.2 to 45.2, p=0.003); (2) patients with VB had much shorter median OS and median PFS than those without (12.3 months vs 18.1 months, p=0.035; 4.5 months vs 7.5 months, p=0.011). Conclusions There was a high risk of VB and a moderate risk of HBVr in HBsAg-positive HBV-HCC patients (with poor long-term HBV DNA control) undergoing ICI and pre-emptive NA therapies. The only risk factor for VB was the pretreatment HBsAg level. Further, VB might be considered as a clinical biomarker predicting inferior OS and PFS in the patients.
Collapse
Affiliation(s)
- Kunyuan Wang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Xia
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yun Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenxuan Yu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yabing Guo
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Li Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Big Data Centre, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
18
|
Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol 2021; 9:769-791. [PMID: 34722192 PMCID: PMC8516840 DOI: 10.14218/jcth.2021.00209] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/20/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030, the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B (CHB). The current guidelines cover recent advances in basic, clinical, and preventive studies of CHB infection and consider the actual situation in China. These guidelines are intended to provide support for the prevention, diagnosis, and treatment of CHB.
Collapse
Affiliation(s)
- Guiqiang Wang
- Center for Liver Diseases, Department of Infectious Diseases, Peking University First Hospital; Department of Infectious and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Zhongping Duan
- Center for Difficult and Complicated Liver Diseases and Artificial Liver, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
19
|
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: 92] [Impact Index Per Article: 23.0] [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
|
|
20
|
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: 50] [Impact Index Per Article: 12.5] [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
|
|
21
|
Chi CT, Lee IC, Lee RC, Hung YW, Su CW, Hou MC, Chao Y, Huang YH. Effect of Transarterial Chemoembolization on ALBI Grade in Intermediate-Stage Hepatocellular Carcinoma: Criteria for Unsuitable Cases Selection. Cancers (Basel) 2021; 13:4325. [PMID: 34503135 PMCID: PMC8431519 DOI: 10.3390/cancers13174325] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 02/08/2023] Open
Abstract
Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration.
Collapse
Affiliation(s)
- Chen-Ta Chi
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Ya-Wen Hung
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| |
Collapse
|
|
22
|
Kim MP, Yang JK, Jun BG, Kim YD, Cheon GJ, Jung HJ, Yoo JJ, Kim SG, Kim YS, Jeong SW, Jang JY, Kim HS, Lee SH. Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma. J Viral Hepat 2021; 28:1011-1018. [PMID: 33759295 DOI: 10.1111/jvh.13508] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/26/2021] [Accepted: 03/08/2021] [Indexed: 12/23/2022]
Abstract
Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.
Collapse
Affiliation(s)
- Myung Pyo Kim
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea
| | - Jae Kook Yang
- Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan, South Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea.,Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea
| | - Young Don Kim
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea
| | - Hee Jae Jung
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine Seoul Hospital, Seoul, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University College of Medicine Seoul Hospital, Seoul, South Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan, South Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan, South Korea
| |
Collapse
|
|
23
|
Toka B, Koksal AS, Eminler AT, Tozlu M, Uslan MI, Parlak E. Comparison of Tenofovir Disoproxil Fumarate and Entecavir in the Prophylaxis of HBV Reactivation. Dig Dis Sci 2021; 66:2417-2426. [PMID: 32729014 DOI: 10.1007/s10620-020-06506-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 07/19/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Current guidelines recommend starting antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in patients receiving immunosuppressive treatments (IST). The aim of this study was to compare the efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prophylaxis. METHODS Patients, who were HBsAg and/or anti-HBc IgG positive and scheduled to receive IST for oncologic and hematologic diseases, were enrolled into the study. Those who were already receiving an antiviral treatment for HBV or had an associated HIV, hepatitis C, D were excluded. The remaining patients with a prophylaxis indication according to the AGA guideline were randomized to receive either ETV (0.5 mg/day) or TDF (245 mg/day). Prophylaxis was continued for 6-12 months after completion of IST. Patients were followed up for 1 year after completion of prophylaxis. The HBV reactivation rates and side effects of the drugs were compared. RESULTS The study group included 120 patients. There was no significant difference between the demographic data, viral serologic parameters and reactivation risk profiles of the ETV (n = 60) and TDF (n = 60) groups. Forty-one patients in the ETV and 36 in the TDF group completed the antiviral prophylaxis, and no HBV reactivation was observed. HBV reactivation was observed in 4 of 37 patients (10.8%) in the ETV group and 5 of 35 (14.3%) patients in the TDF group (including one with flare) during the follow-up after completion of prophylaxis. Ten patients in the ETV group (16.7%) and 14 patients (23.3%) in the TDF group experienced side effects (p = 0.77). One patient in the TDF group had to switch to ETV due to severe itchy, maculopapular rash-like lesions. CONCLUSIONS ETV and TDF had a similar efficacy in the prophylaxis of HBV reactivation in patients undergoing IST, with none of the patients experiencing reactivation.
Collapse
Affiliation(s)
- Bilal Toka
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya, Turkey.
| | - Aydin Seref Koksal
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya, Turkey
| | - Ahmet Tarik Eminler
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya, Turkey
| | - Mukaddes Tozlu
- Department of Gastroenterology, Sakarya Eğitim ve Araştırma Hastanesi, Sakarya, Turkey
| | - Mustafa Ihsan Uslan
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya, Turkey
| | - Erkan Parlak
- Department of Gastroenterology, Faculty of Medicine, Sakarya University, Korucuk Campus, Sakarya, Turkey
| |
Collapse
|
|
24
|
Liu S, Lai J, Lyu N, Xie Q, Cao H, Chen D, He M, Zhang B, Zhao M. Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy. Front Oncol 2021; 10:582504. [PMID: 33614477 PMCID: PMC7890701 DOI: 10.3389/fonc.2020.582504] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 12/16/2020] [Indexed: 01/27/2023] Open
Abstract
Background This study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients. Methods We enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups. Results A total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36–0.91; p<0.05). Conclusions HBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients. Name of the Trial Register HAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC. Clinical Trial Registration https://www.clinicaltrials.gov/, identifier NCT 02436044
Collapse
Affiliation(s)
- Shousheng Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of the General Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jinfa Lai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ning Lyu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qiankun Xie
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Huijiao Cao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of the General Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Dabiao Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Meng He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Bei Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of the General Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ming Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| |
Collapse
|
|
25
|
Lei T, Tan F, Hou Z, Liu P, Zhao X, Liu H. Hepatitis B Virus Reactivation in Gastrointestinal Stromal Tumor Patients Treated With Imatinib. Front Oncol 2021; 10:596500. [PMID: 33552970 PMCID: PMC7862776 DOI: 10.3389/fonc.2020.596500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose Hepatitis B virus reactivation (HBVr) in patients with gastrointestinal stromal tumors (GISTs) have not been sufficiently characterized. This study aimed to review the possible mechanism of HBVr induced by imatinib and explore appropriate measures for patient management and monitoring. Methods The clinical data of GIST patients who experienced HBVr due to treatment with imatinib at Xiangya Hospital (Changsha, Hunan, China) were retrospectively analyzed. A literature review was also conducted. Results Five cases were analyzed, including 3 cases in this study. The average age of the patients was 61.8 y, with male preponderance (4 of 5 vs. 1 of 5). These patients received imatinib as adjuvant treatment (n=4) or as neoadjuvant treatment (n=1). Primary tumors were mostly located in the stomach (n=4) or rectum (n=1). High (n=3) or intermediate (n=1) recurrence risk was categorized using the postoperative pathological results (n=4). Imatinib was then started at 400 (n=4) or 200 mg (n=1) daily. Patients first reported abnormal liver function during the 2th (n=1),6th (n=3), or 10th (n=1) month of treatment with imatinib. Some patients (n=4) discontinued imatinib following HBVr; notably, 1 month after discontinuation, 1 patient experienced HBVr. Antivirals (entecavir n=4, tenofovir n=1), artificial extracorporeal liver support (n=1), and liver transplant (n=1) were effective approaches to treating HBVr. Most patients (n=3) showed favorable progress, 1 patient underwent treatment, and 1 patient died due to severe liver failure induced by HBVr. Conclusions Although HBVr is a rare complication (6.12%), HBV screening should be conducted before starting treatment with imatinib in GIST patients. Prophylactic therapy for hepatitis B surface antigen positive patients, prompt antiviral treatment and cessation of imatinib are also necessary.
Collapse
Affiliation(s)
- Tianxiang Lei
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Fengbo Tan
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Zhouhua Hou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Peng Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Xianhui Zhao
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Heli Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
26
|
Hepatitis B Virus Reactivation Potential Risk Factors in Hepatocellular Carcinoma via Transcatheter Arterial Chemoembolization: A Retrospective Research. Can J Gastroenterol Hepatol 2021; 2021:8864655. [PMID: 33505945 PMCID: PMC7815398 DOI: 10.1155/2021/8864655] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 12/06/2020] [Accepted: 12/28/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research. METHODS A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. RESULTS HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥104 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases (24.3%, 17/70). Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group. CONCLUSION Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients.
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
|
Kim BH, Park JW. Antiviral Therapy in Liver Cancer. RADIOTHERAPY OF LIVER CANCER 2021:59-69. [DOI: 10.1007/978-981-16-1815-4_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
29
|
Ziogas DC, Kostantinou F, Cholongitas E, Anastasopoulou A, Diamantopoulos P, Haanen J, Gogas H. Reconsidering the management of patients with cancer with viral hepatitis in the era of immunotherapy. J Immunother Cancer 2020; 8:jitc-2020-000943. [PMID: 33067316 PMCID: PMC7570225 DOI: 10.1136/jitc-2020-000943] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2020] [Indexed: 12/15/2022] Open
Abstract
In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this therapeutic panel. Among the ICPIs-treated cases with prior viral hepatitis, we focus further on those experienced HBV or HCV reactivation and discuss their host, tumor and serological risk factors, their antiviral and immunological management as well as their hepatitis and tumor outcome. Based on a low level of evidence, immunotherapy in these specific cancer cases seems to be associated with no inferior efficacy and with a relevantly low reactivation rate. However, hepatitis reactivation and subsequent irreversible complications appeared to have poor response to deferred antiviral treatment. While, the prophylactic use of modern antiviral drugs could eliminate or diminish up front the viral load in most cases, leading to cure or long-term hepatitis control. Taking together the clinical significance of preventive therapy, the low but existing reactivation risk and the potential immune-related hepatotoxicity, a comprehensive baseline assessment of liver status, including viral hepatitis screening, before the onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.
Collapse
Affiliation(s)
- Dimitrios C Ziogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Frosso Kostantinou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Amalia Anastasopoulou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Panagiotis Diamantopoulos
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - John Haanen
- Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Helen Gogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| |
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
|
Yim HJ, Kim JH, Park JY, Yoon EL, Park H, Kwon JH, Sinn DH, Lee SH, Lee JH, Lee HW. Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop. Clin Mol Hepatol 2020; 26:411-429. [PMID: 32854458 PMCID: PMC7641563 DOI: 10.3350/cmh.2020.0049] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 06/21/2020] [Indexed: 02/06/2023] Open
Abstract
Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.
Collapse
Affiliation(s)
- Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea
| | - Hana Park
- Department of Health Medicine, Asan Medical Center, Seoul, Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Chonan, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
32
|
Jang JW, Yoo SH, Nam HC, Jang BH, Sung Sung PS, Lee W, Kwon JH, Nam SW, Bae SH, Yoon SK, Choi JY. Association of Prophylactic Anti-Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy. Clin Infect Dis 2020; 71:546-555. [PMID: 31504352 DOI: 10.1093/cid/ciz860] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 08/30/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). METHODS Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. RESULTS A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. CONCLUSIONS Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.Hepatitis B virus-associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.
Collapse
Affiliation(s)
- Jeong Won Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Sun Hong Yoo
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Hee Chul Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Bo Hyun Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Pil Soo Sung Sung
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Won Lee
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Soon Woo Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| |
Collapse
|
|
33
|
Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
Collapse
Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
| |
Collapse
|
|
34
|
Kim J, Chung SJ, Sinn DH, Lee KW, Park JB, Huh W, Lee JE, Jang HR, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients. J Viral Hepat 2020; 27:739-746. [PMID: 32057171 DOI: 10.1111/jvh.13279] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/18/2020] [Accepted: 01/27/2020] [Indexed: 12/11/2022]
Abstract
Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis B core (HBc)-positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6-12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short-term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg-negative and anti-HBc-positive KT recipients were analysed for HBV reactivation. During a median follow-up of 6.7 (interquartile range: 4.2-9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4-11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti-HBs-negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post-KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.
Collapse
Affiliation(s)
- Jihye Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Se Jin Chung
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyo Won Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wooseong Huh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Eun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hye Ryoun Jang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
35
|
Meyers BM, Knox J, Cosby R, Beecroft JR, Chan KKW, Coburn N, Feld J, Jonker D, Mahmud A, Ringash J. Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline. ACTA ACUST UNITED AC 2020; 27:e106-e114. [PMID: 32489260 DOI: 10.3747/co.27.5891] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy, compared with those standards, is not well known. Methods First, systematic review questions were developed. Literature searches of the medline, embase, and Cochrane library databases (January 2000 to July 2018 or January 2005 to July 2018 depending on the question) were conducted; in addition, abstracts from the 2018 annual meeting of the American Society of Clinical Oncology were reviewed. A practice guideline was drafted that was then scrutinized by internal and external reviewers. Results Seventy-seven studies were included in the guideline: no guidelines, two systematic reviews, and seventy-five primary studies published in full (including one pooled analysis). Five recommendations were developed. Conclusions There is no evidence for or against the use of local or regional interventions other than transarterial chemoembolization for the treatment of intermediate- or advanced-stage hcc. Furthermore, there is no evidence to support the addition of sorafenib to any local or regional therapy. Sorafenib or lenvatinib are recommended for first-line systemic treatment of intermediate-stage hcc. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment. Antiviral treatment is recommended in individuals with advanced hcc who are positive for the hepatitis B surface antigen.
Collapse
Affiliation(s)
- B M Meyers
- Juravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, ON
| | - J Knox
- Princess Margaret Cancer Centre, Toronto, ON
| | - R Cosby
- Program in Evidence-Based Care, Department of Oncology, McMaster University, Hamilton, ON
| | - J R Beecroft
- Department of Medical Imaging, Mount Sinai Hospital, and University Health Network, Toronto, ON
| | - K K W Chan
- Sunnybrook Odette Cancer Centre, Toronto, ON
| | - N Coburn
- Sunnybrook Odette Cancer Centre, Toronto, ON
| | - J Feld
- Toronto General Hospital Research Institute, Toronto, ON
| | - D Jonker
- The Ottawa Hospital Cancer Centre, Ottawa, ON
| | - A Mahmud
- Cancer Centre of Southeastern Ontario, Kingston, ON
| | - J Ringash
- Princess Margaret Cancer Centre, Toronto, ON.,Department of Radiation Oncology, University of Toronto, Toronto, ON
| | | |
Collapse
|
|
36
|
Zou X, Guo L, Gu Y, Yang Z, Huang P, Liu T, Zhao J, Wu G. Optimal timing of antiviral therapy for patients with malignant tumor who presented with hepatitis B reactivation during chemotherapy and/or immunosuppressive therapy. J Cancer 2020; 11:3559-3566. [PMID: 32284752 PMCID: PMC7150462 DOI: 10.7150/jca.40154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 02/22/2020] [Indexed: 11/05/2022] Open
Abstract
Background: Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or immunotherapy. Antiviral prophylaxis is recommended for all patients who are hepatitis B surface antigen (HBsAg)-positive during chemotherapy and/or immunosuppressive therapy. However, the optimal timing of antiviral therapy before chemotherapy and/or immunosuppressive therapy is not fully elucidated. Patients and methods: We retrospectively evaluated 446 HBsAg-positive patients who underwent chemotherapy and/or immunosuppressive therapy. The cumulative rates of HBV reactivation were evaluated using the Kaplan-Meier method and were compared using the log-rank test. The risk factors of HBV reactivation were examined via univariate and multivariate analyses using the Cox proportional hazards model. Results: The cumulative HBV reactivation rates of patients who received antiviral therapy before chemotherapy and/or immunosuppressive therapy were significantly lower than those of patients who received antiviral therapy after chemotherapy and/or immunosuppressive therapy (P = 0.002). The incidence of HBV reactivation was significantly different between patients who received antiviral therapy at least 1 day before chemotherapy and/or immunosuppressive therapy and those who did not (P = 0.006). No significant difference was observed in the HBV reactivation rates between patients who received antiviral therapy at least 2 days (P = 0.310), 3 days (P = 0.494), and 1 week (P = 0.655) before chemotherapy and/or immunosuppressive therapy and those who did not. The multivariate Cox proportional hazards model showed that women had a lower risk of developing HBV reactivation than men (P = 0.025). The use of the prophylactic antiviral agent entecavir, compared with lamivudine and telbivudine, was associated with the decreased risk of developing HBV reactivation (P = 0.002). Conclusion: HBsAg-positive patients who received preemptive antiviral therapy after chemotherapy and/or immunosuppressive therapy had a high risk of developing HBV reactivation. However, it is not necessary for patients to receive antiviral therapy at least 1 week before chemotherapy and/or immunosuppressive therapy.
Collapse
Affiliation(s)
- Xiaofang Zou
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Longhua Guo
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Yinfang Gu
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Zhijun Yang
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Ping Huang
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Tianhuang Liu
- Department of Hepatopathy, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
| | - Jingjing Zhao
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guowu Wu
- Department of Medical Oncology, Cancer Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China
- Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, China
| |
Collapse
|
|
37
|
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
|
|
38
|
Abd El Aziz MA, Sacco R, Facciorusso A. Nucleos(t)ide analogues and Hepatitis B virus-related hepatocellular carcinoma: A literature review. Antivir Chem Chemother 2020; 28:2040206620921331. [PMID: 32418480 PMCID: PMC7232045 DOI: 10.1177/2040206620921331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 04/01/2020] [Indexed: 01/10/2023] Open
Abstract
Hepatitis B virus is mainly considered to cause hepatocellular carcinoma which is the fourth leading cause of cancer-related mortality worldwide. Treatment of Hepatitis B virus with nucleos(t)ide analogues can decrease the progression of the disease and subsequently decreases the incidence of hepatocellular carcinoma. In this review, we have discussed the different classes of nucleos(t)ide analogues used in the treatment of Hepatitis B virus and their relationship with the development of hepatocellular carcinoma. Furthermore, we discussed the effect of treatment of Hepatitis B virus with Nucleoside analogues (NAs) before, during and after surgery, chemoembolization, radiofrequency ablation, and chemotherapy for the treatment of hepatocellular carcinoma.
Collapse
Affiliation(s)
| | - Rodolfo Sacco
- Department of Medical Sciences, Section of Gastroenterology,
University of Foggia, Foggia Italy
| | - Antonio Facciorusso
- Department of Medical Sciences, Section of Gastroenterology,
University of Foggia, Foggia Italy
| |
Collapse
|
|
39
|
Kim JH. 2018 Korean Association for the Study of the Liver (KASL) Clinical Practice Guidelines of Chronic Hepatitis B: What's Different? THE KOREAN JOURNAL OF GASTROENTEROLOGY 2019; 73:132-140. [PMID: 31013556 DOI: 10.4166/kjg.2019.73.3.132] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 03/08/2019] [Accepted: 03/08/2019] [Indexed: 12/14/2022]
Abstract
The clinical practice guideline for the management of chronic hepatitis B (CHB) was originally enacted in 2004 by the Korean Association for the Study of the Liver in order to provide medical practitioners with specific medical information regarding CHB to help them facilitate their understanding of the disease and treatment of the infected patients. Other than an update on the treatment of antiviral resistance in 2014, which is a partial revision, the guidelines for the treatment of chronic hepatitis B have been revised entirely three times in 2007, 2011, and 2015. Although several major international liver association have established and revised clinical practice guidelines, since the medical environment in each country is somewhat different depending on race, region, institution, and economic conditions, it is necessary to revise the Korean guidelines to that reflect our medical environment and own research results. In this review, major change and its background will be summarized about 2018 updated clinical practice guidelines for the management of CHB.
Collapse
Affiliation(s)
- Ji Hoon Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| |
Collapse
|
|
40
|
Kim TS, Sinn DH, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia. J Gastroenterol Hepatol 2019; 34:2028-2035. [PMID: 31157456 DOI: 10.1111/jgh.14750] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 05/23/2019] [Accepted: 05/27/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Clinical course of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients presenting with low-level viremia (LLV) is unclear. METHODS A total of 565 HBV-related HCC patients with LLV (detectable but HBV DNA ≤ 2000 IU/mL) at the time of HCC diagnosis were analyzed. Based on patterns of HBV DNA levels during follow-up, patients were categorized into three groups: maintained virologic remission (MVR), LLV, and flare. Overall survival was compared between those three groups. RESULTS During a median 4.5 years of follow-up, 33% showed MVR, 39% showed LLV, and 28% experienced flare. The overall survival differed between MVR, LLV, and flare groups (5-year overall survival: 74.3%, 67.3%, and 61.7%, respectively, 0.015). The patterns of HBV DNA levels were independent factors associated with overall survival, along with age, antiviral treatment, Barcelona clinic liver cancer stage, and initial treatment modality. Flare group showed increased risk of mortality (adjusted hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.15-2.55) compared with MVR group, while the risk was statistically marginal for the LLV group (adjusted HR 1.39, 95% CI 0.95-2.04). During follow-up, 183 patients (32.4%) newly started antiviral therapy (AVT) at LLV. Flare risk was significantly lower among patients who started AVT at LLV compared with those who did not (adjusted HR 0.26, 95% CI 0.17-0.38). CONCLUSIONS Among HBV-related HCC patients with LLV, flare was frequent during follow-up and was associated with poorer overall survival compared with MVR group. Prospective studies that address whether inducing MVR by early AVT improves patient outcome are warranted.
Collapse
Affiliation(s)
- Tae-Se Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
41
|
Abstract
PURPOSE OF REVIEW To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns. RECENT FINDINGS The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients. SUMMARY Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.
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: 03/17/2019] [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
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
44
|
Zhang SS, Liu JX, Zhu J, Xiao MB, Lu CH, Ni RZ, Qu LS. Effects of TACE and preventive antiviral therapy on HBV reactivation and subsequent hepatitis in hepatocellular carcinoma: a meta-analysis. Jpn J Clin Oncol 2019; 49:646-655. [PMID: 30968933 DOI: 10.1093/jjco/hyz046] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 03/02/2019] [Accepted: 03/09/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIM The impact of transarterial chemoembolization (TACE) and preventive antiviral therapy on the occurrence of hepatitis B virus (HBV) reactivation and subsequent hepatitis remains controversial. This meta-analysis aimed to evaluate the effect of TACE and preventive antiviral therapy on the risk of HBV reactivation and subsequent hepatitis. Meanwhile, we explored the role of HBeAg status in HBV reactivation after TACE. METHODS We performed this meta-analysis with 11 included studies to assess the effect of TACE and preventive antiviral therapy on predicting clinical outcomes in HBV-related hepatocellular carcinoma (HCC). The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Central Register of Controlled were searched for the included articles (from 2000 to December 2017). RESULTS Our results showed that TACE significantly increased the risk of HBV reactivation (OR: 3.70; 95% CI 1.45-9.42; P < 0.01) and subsequent hepatitis (OR: 4.30; 95% CI 2.28-8.13; P < 0.01) in HCC patients. There was no significant difference in HBV reactivation after TACE between HBeAg positive and negative patients (OR: 1.28; 95% CI 0.31-5.34; P = 0.73). Preventive antiviral therapy could statistically reduce the rate of HBV reactivation (OR: 0.08; 95% CI 0.02-0.32; P < 0.01) and hepatitis (OR: 0.22; 95% CI 0.06-0.80; P = 0.02) in those with TACE treatment. CONCLUSIONS The present study suggested that TACE was associated with a higher possibility of HBV reactivation and subsequent hepatitis. Preventive antiviral therapy is significantly in favor of a protective effect.
Collapse
Affiliation(s)
- Su-Su Zhang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Jin-Xia Liu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Jing Zhu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Ming-Bing Xiao
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Cui-Hua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Run-Zhou Ni
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Li-Shuai Qu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China
| |
Collapse
|
|
45
|
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: 165] [Impact Index Per Article: 27.5] [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
|
|
46
|
Doyle J, Raggatt M, Slavin M, McLachlan S, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust 2019; 210:462-468. [DOI: 10.5694/mja2.50160] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Joseph Doyle
- Monash University Melbourne VIC
- Disease Elimination ProgramBurnet Institute Melbourne VIC
- Alfred Health Melbourne VIC
| | - Michelle Raggatt
- Disease Elimination ProgramBurnet Institute Melbourne VIC
- Alfred Health Melbourne VIC
| | - Monica Slavin
- Peter MacCallum Cancer Institute Melbourne VIC
- University of Melbourne Melbourne VIC
| | - Sue‐Anne McLachlan
- University of Melbourne Melbourne VIC
- St Vincent's Hospital Melbourne VIC
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver CentreRoyal Prince Alfred Hospital Sydney NSW
- University of Sydney Sydney NSW
| | - Joseph J Sasadeusz
- Alfred Health Melbourne VIC
- Victorian Infectious Diseases ServiceRoyal Melbourne Hospital Melbourne VIC
| | | | | | - Harshal Nandurkar
- Monash University Melbourne VIC
- Australian Centre for Blood Diseases Melbourne VIC
| | - Anna Johnston
- Royal Hobart Hospital Hobart TAS
- University of Tasmania Hobart TAS
| | | | | |
Collapse
|
|
47
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
48
|
|
|
49
|
Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
Collapse
|
|
50
|
|