Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
J Clin Microbiol. 2019 Jan 2;57(1). doi: 10.1128/JCM.01303-18. Print 2019 Jan.
The purpose of this study was to explore the correlations of serum hepatitis B core-related antigen (HBcrAg) with intrahepatic Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV total DNA in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Serum HBcrAg and other parameters, including HBV DNA, HBV RNA, HBeAg, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were quantitatively measured at baseline and follow-up time points. Intrahepatic HBV cccDNA and total DNA were quantitatively detected at baseline and 96 weeks. Grading of liver necroinflammation and staging of hepatic fibrosis were assessed at baseline and 96 weeks. Correlations between serum HBcrAg and other parameters were analyzed by Pearson's correlation analysis. The results showed that pretreatment HBcrAg correlated significantly with HBV total DNA levels ( = 0.328, 0.003) in 82 CHB patients, and, after removing three outliers, with intrahepatic HBV cccDNA ( = 0.323, 0.004; = 79). Serum HBcrAg correlated better with HBV cccDNA in patients with lower levels of serum HBV DNA (stratified by 7 log IU/ml of HBV DNA; = 0.656, 0.003 versus = -0.02, = 0.866). Significant inverse correlations were found between HBcrAg and grade of liver necroinflammation ( = -0.245, 0.037), stage of hepatic fibrosis ( = -0.360, 0.002) at baseline. Serum HBcrAg presented significant correlation with intrahepatic HBV cccDNA in patients with HBeAg seroconversion at 96 weeks ( = 0.622, 0.006). The decrease in HBcrAg showed significant correlation with the decrease in HBV cccDNA after 96-week NA therapy ( = 0.282, 0.043). Serum HBcrAg also correlated significantly with other serum markers at baseline and 96 weeks of NA therapy. In conclusion, baseline HBcrAg and its decreased value were significantly correlated with the corresponding intrahepatic HBV cccDNA.
本研究旨在探讨乙型肝炎 e 抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者血清乙型肝炎核心相关抗原（HBcrAg）与肝内乙型肝炎病毒（HBV）共价闭合环状 DNA（cccDNA）和 HBV 总 DNA 的相关性。在基线和随访时间点定量检测血清 HBcrAg 及其他参数，包括 HBV DNA、HBV RNA、HBeAg、乙型肝炎表面抗原（HBsAg）、乙型肝炎核心抗体（抗-HBc）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。在基线和 96 周时定量检测肝内 HBV cccDNA 和总 DNA。在基线和 96 周时评估肝组织坏死炎症分级和肝纤维化分期。采用 Pearson 相关分析分析血清 HBcrAg 与其他参数的相关性。结果显示，在 82 例 CHB 患者中，治疗前 HBcrAg 与 HBV 总 DNA 水平显著相关（ = 0.328，P<0.003），去除 3 个离群值后，与肝内 HBV cccDNA 也显著相关（ = 0.323，P<0.004； = 79）。在血清 HBV DNA 水平较低的患者中（按 HBV DNA 7 log IU/ml 分层； = 0.656，P<0.003 与 = -0.02，P=0.866），血清 HBcrAg 与 HBV cccDNA 的相关性更好。在基线时，HBcrAg 与肝组织坏死炎症分级（ = -0.245，P=0.037）和肝纤维化分期（ = -0.360，P<0.002）呈显著负相关。在 96 周时 HBeAg 血清学转换的患者中，血清 HBcrAg 与肝内 HBV cccDNA 呈显著相关（ = 0.622，P<0.006）。NA 治疗 96 周后 HBcrAg 下降与 HBV cccDNA 下降呈显著相关（ = 0.282，P<0.043）。血清 HBcrAg 与 NA 治疗基线和 96 周时的其他血清标志物也呈显著相关。结论：基线 HBcrAg 及其下降值与相应的肝内 HBV cccDNA 显著相关。
