High Level of Hepatitis B Core-Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load.


Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
12 2019
Historique:
received: 28 04 2018
revised: 18 08 2019
accepted: 20 08 2019
pubmed: 31 8 2019
medline: 1 1 2020
entrez: 31 8 2019
Statut: ppublish

Résumé

Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core-related antigen (HBcrAg) have been associated with active replication of HBV. We investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment. We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development. HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load [IVL]) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27-17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%-0.24%). In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.

Sections du résumé

BACKGROUND & AIMS
Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core-related antigen (HBcrAg) have been associated with active replication of HBV. We investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment.
METHODS
We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development.
RESULTS
HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load [IVL]) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27-17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%-0.24%).
CONCLUSIONS
In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.

Identifiants

pubmed: 31470004
pii: S0016-5085(19)41248-1
doi: 10.1053/j.gastro.2019.08.028
pii:
doi:

Substances chimiques

Biomarkers 0
DNA, Circular 0
DNA, Viral 0
Hepatitis B Antigens 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1518-1529.e3

Informations de copyright

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Tai-Chung Tseng (TC)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

Chun-Jen Liu (CJ)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Chen-Yang Hsu (CY)

Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Chun-Ming Hong (CM)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Tung-Hung Su (TH)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

Wan-Ting Yang (WT)

Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

Chi-Ling Chen (CL)

Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Hung-Chih Yang (HC)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.

Yen-Tsung Huang (YT)

Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

Stephanie Fang-Tzu Kuo (S)

Royal Hobart Hospital, Hobart, Australia.

Chen-Hua Liu (CH)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

Pei-Jer Chen (PJ)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Ding-Shinn Chen (DS)

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Jia-Horng Kao (JH)

Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kaojh@ntu.edu.tw.

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