期刊
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
卷 36, 期 10, 页码 2943-2951出版社
WILEY
DOI: 10.1111/jgh.15563
关键词
Hepatitis B core-related antigen (HBcrAg); Hepatitis B virus (HBV); Hepatocellular carcinoma (HCC); Nucleoside; nucleotide analogs (NAs)
资金
- Japan Agency for Medical Research and Development [JP20fk0210067h0001]
This study investigated the virological characteristics of HBcrAg in CHB patients and the factors associated with HCC risk in HBeAg-negative patients. Results showed that higher levels of HBcrAg in HBeAg-negative patients were associated with cirrhosis and higher HBV DNA levels, and were an independent predictive factor for HCC development in patients receiving NA therapy.
Background and Aim The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients. Methods Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1 year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients. Results Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (> 6.8 vs 3.7 log U/mL, P < 0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis = 3.5/4.7 log U/mL, P = 0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1 year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1 log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P < 0.01) and even in non-cirrhosis patients. Conclusion Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.
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