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Hepatitis B core‐related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen‐negative chronic hepatitis B patients

医学 恩替卡韦 肝细胞癌 胃肠病学 内科学 HBeAg 乙型肝炎 肝硬化 乙型肝炎病毒 肝病学 危险系数 乙型肝炎表面抗原 免疫学 置信区间 拉米夫定 病毒
作者
Shun Kaneko,Masayuki Kurosaki,Kento Inada,Sakura Kirino,Yuka Hayakawa,Koji Yamashita,Leona Osawa,Shuhei Sekiguchi,Masakazu Higuchi,Kenta Takaura,Chiaki Maeyashiki,Nobuharu Tamaki,Yutaka Yasui,Jun Itakura,Yuka Takahashi,Kaoru Tsuchiya,Hiroyuki Nakanishi,Namiki Izumi
出处
期刊:Journal of Gastroenterology and Hepatology [Wiley]
卷期号:36 (10): 2943-2951 被引量:12
标识
DOI:10.1111/jgh.15563
摘要

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.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.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.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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