World J Gastroenterol. 2019 Aug 28;25(32):4764-4778. doi: 10.3748/wjg.v25.i32.4764.
On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B.
Chang XJ1, Sun C2, Chen Y3, Li XD4, Yu ZJ5, Dong Z3, Bai WL3, Wang XD6, Li ZQ5, Chen D7, Du WJ8, Liao H9, Jiang QY4, Sun LJ4, Li YY3, Zhang CH4, Xu DP4, Chen YP6, Li Q7, Yang YP1.
Author information
1
Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China.
2
Peking University 302 Clinical Medical School, Beijing 100039, China.
3
Department of Therapeutic Research for Liver Cancer, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
4
Department of Research for Clinical Medicine, the Fifth Medical center of Chinese PLA General Hospital, Beijing 100039, China.
5
Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
6
Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
7
Fuzhou Infectious Diseases Hospital, Fuzhou 350025, Fujian Province, China.
8
Medical Department Training Graduate Office, Chinese PLA General Hospital, Beijing 100853, China.
9
Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Abstract
BACKGROUND:
Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.
AIM:
To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.
METHODS:
This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.
RESULTS:
Level of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.
CONCLUSION:
HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.
KEYWORDS:
Cirrhosis; Hepatitis B core-related antigen; Liver fibrosis; On-treatment monitoring