Serum hepatitis B core-related antigen level stratifies risk of disease progression in chronic hepatitis B patients with intermediate viral load
Tai-Chung Tseng 1 2 3 , Chun-Jen Liu 1 2 4 , Wan-Ting Yang 2 , Chen-Yang Hsu 5 , Chun-Ming Hong 1 6 , Tung-Hung Su 1 2 , Cheng-Hsueh Tsai 2 , Chi-Ling Chen 4 , Hung-Chih Yang 1 2 4 7 , Chen-Hua Liu 1 2 , Hsiu-Hsi Chen 5 , Pei-Jer Chen 1 2 4 , Jia-Horng Kao 1 2 3 4
Affiliations
Affiliations
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
2
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
3
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
4
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan.
5
Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
6
Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
7
Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan.
PMID: 33465271 DOI: 10.1111/apt.16266
Abstract
Background: Patients with chronic hepatitis B virus (HBV) infection are at risk of developing liver disease. Serum hepatitis B core-related antigen (HBcrAg) is a new biomarker for intrahepatic templates for HBV replication.
Aim: To explore whether a high HBcrAg level is associated with increased risk of cirrhosis, especially in patients with intermediate viral load (HBV DNA 2000-19 999 IU/mL) due to their moderate risk of disease progression.
Methods: A total of 1673 treatment-naïve, non-cirrhotic patients with negative hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) level <40 U/L at baseline were enrolled. We explored the relationship between baseline levels of HBcrAg and cirrhosis development in all patients, and whether a higher HBcrAg level (<10 vs ≥10 KU/mL) was associated with an increased risk of disease progression in those with intermediate viral load.
Results: Of the 1673 patients, 104 developed cirrhosis after a mean follow-up of 15.9 years. Higher HBcrAg levels were associated with increased incidence of cirrhosis, cirrhosis-related complications, and liver-related death. In 445 patients with intermediate viral load, the cirrhosis risk stratified by HBcrAg level of 10 KU/mL yielded a hazard ratio of 3.22 (95% CI: 1.61-6.47). The risk stratification remained significant when exploring other pre-cirrhosis endpoints, including HBeAg-negative hepatitis, hepatitis flare, and HBV DNA >20 000 IU/mL after 3 years of follow-up.
Conclusions: In HBeAg-negative patients with normal ALT levels, higher HBcrAg levels are associated with increased risk of cirrhosis. Among those with intermediate viral load, HBcrAg <10 KU/mL defines a low-risk group for disease progression.