Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.


Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
02 2020
Historique:
received: 21 02 2019
revised: 17 06 2019
accepted: 03 07 2019
pubmed: 16 7 2019
medline: 19 8 2021
entrez: 16 7 2019
Statut: ppublish

Résumé

Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

Sections du résumé

BACKGROUND & AIMS
Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response.
METHODS
Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response.
RESULTS
There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events.
CONCLUSIONS
In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

Identifiants

pubmed: 31306800
pii: S1542-3565(19)30743-8
doi: 10.1016/j.cgh.2019.07.010
pii:
doi:

Substances chimiques

Antiviral Agents 0
entecavir 5968Y6H45M
Guanine 5Z93L87A1R

Banques de données

ClinicalTrials.gov
['NCT00388674']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

457-467.e21

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Jin-Lin Hou (JL)

Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: jlhousmu@163.com.

Wei Zhao (W)

Department of Infectious Diseases, 2nd Hospital Nanjing, Nanjing, China.

Changhyeong Lee (C)

Daegu Catholic University Hospital, Daegu, Korea.

Hie-Won Hann (HW)

Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Cheng-Yuan Peng (CY)

Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

Tawesak Tanwandee (T)

Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.

Viacheslav Morozov (V)

LLC Medical Company "Hepatolog," Samara, Russian Federation.

Hartwig Klinker (H)

Department of Medicine II, Division of Hepatology, University of Würzburg Medical Center, Würzberg, Germany.

Jose D Sollano (JD)

Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines.

Adrian Streinu-Cercel (A)

Department of Infectious Diseases I, Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases, "Prof. Dr. Matei Bals," Bucharest, Romania.

Hugo Cheinquer (H)

Gastroenterology and Hepatology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.

Qing Xie (Q)

Department of Infectious Diseases, Shanghai Rui Jin Hospital, Shanghai, China.

Yu-Ming Wang (YM)

Institute for Infectious Diseases, Southwest Hospital, Chongqing, China.

Lai Wei (L)

Hepatology Department, Peking University People's Hospital, Beijing, China.

Ji-Dong Jia (JD)

National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capitol Medical University, Beijing, China.

Guozhong Gong (G)

Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha, China.

Kwang-Hyub Han (KH)

Department of Internal Medicine, Institute of Gastroenterology and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Wukui Cao (W)

Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China.

Mingliang Cheng (M)

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, China.

Xiaoping Tang (X)

Department of Infectious Diseases, Guangzhou No. 8 People's Hospital, Guangzhou, China.

Deming Tan (D)

Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China.

Hong Ren (H)

Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Zhongping Duan (Z)

Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.

Hong Tang (H)

Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.

Zhiliang Gao (Z)

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Shijun Chen (S)

Hepatology Department, Jinan Infectious Disease Hospital, Jinan, China.

Shumei Lin (S)

Department of Infectious Diseases, The First Affiliated Hospital of Xi'An Jiaotong University, Xi'An, China.

Jifang Sheng (J)

Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Chengwei Chen (C)

Hepatology Department, 85th Hospital of People's Liberation Army, Shanghai, China.

Jia Shang (J)

Department of Infectious Diseases, Henan Provincial People's hospital, Zhengzhou, China.

Tao Han (T)

Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China.

Yanyan Ji (Y)

Hepatology Department, Shanghai Jing'an District Central Hospital, Shanghai, China.

Junqi Niu (J)

Hepatobiliary Medical Ward, The First Hospital of Jilin University, Changchun, China.

Jian Sun (J)

Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Yongpeng Chen (Y)

Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Elizabeth L Cooney (EL)

Bristol-Myers Squibb, Inc, Wallingford, Connecticut.

Seng-Gee Lim (SG)

Division of Gastroenterology and Hepatology, National University Health System, National University of Singapore, Singapore.

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