血清抗-HBc与ALT串联HBV复制标志物识别HBeAg阳性慢性HBV感染非活动性肝炎的性能

摘要/Abstract

摘要： 目的探讨血清抗-HBc、ALT及HBsAg、HBcrAg、HBV DNA识别HBeAg阳性慢性HBV感染非活动性肝炎(NAH)的功能截断值,对比评价抗-HBc与ALT串联HBsAg、HBcrAg、HBV DNA识别HBeAg阳性NAH的性能。方法纳入2011年2月至2018年8月上海市公共卫生临床中心176例抗病毒治疗的HBeAg 阳性患者,随访6.0～129.0个月,其中43例发生了自发性HBeAg血清转换(ESC)。根据ROC曲线序贯Kaplan-Meier生存分析,指定抗-HBc、ALT及HBsAg、HBcrAg、HBV DNA预测自发性ESC和识别HBeAg阳性NAH终止的功能截断值。结果抗-HBc ≤3 lgIU/mL、ALT ≤60 U/L及HBsAg >4.602 lgIU/mL、HBcrAg >5.477 lgkU/mL、HBV DNA >7.477 lgIU/mL为识别HBeAg阳性NAH的功能截断值。基于功能截断值,低水平抗-HBc串联高水平HBsAg、HBcrAg、HBV DNA识别基线肝脏病理学分级≤G1且分期≤S1的灵敏度和特异度分别为17.6% 和94.9%、15.7%和96.6%、15.7%和91.5%,阳性和阴性似然比分别为3.451和0.868、4.618和0.873、1.847和0.921;低水平ALT串联高水平HBsAg、HBcrAg、HBV DNA识别基线肝脏病理学分级≤G1且分期≤S1的灵敏度和特异度分别为30.6%和85.7%、31.8%和89.0%、34.1%和79.1%,阳性和阴性似然比分别为2.140和0.810、2.891和0.766、1.632和0.833。结论低水平抗-HBc和低水平ALT串联高水平HBsAg、HBcrAg、HBV DNA均可有效识别HBeAg阳性NAH且其效能接近、性能相似。

关键词: 乙型肝炎核心抗体, 丙氨酸氨基转移酶, 乙型肝炎表面抗原, 乙型肝炎核心相关抗原, 自然史

Abstract: Objective To re-explore the functional cutoff values for serum hepatitis B core antibody (anti-HBc), alanine transaminase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) and hepatitis B virus (HBV) DNA in identifying hepatitis B e antigen (HBeAg)-positive non-aggressive hepatitis (NAH) in patients with chronic HBV infection, in the context of disaffiliating the criteria for the natural history phases that have always been subject to disagreements and controversies, and to reappraise the performance of anti-HBc versus ALT tandem HBsAg, HBcrAg, and HBV DNA in identifying HBeAg-positive NAH. Methods 176 HBeAg-positive patients were enrolled from Shanghai Public Health Clinical Center between Feburary 2011 and August 2018, they were without antiviral therapy and followed up for 6.0 to 129.0 months, of which 43 patients had experienced spontaneous HBeAg sero-conversion (ESC). According to the sequential Kaplan-Meier survival analyses based on receiver operating characteristic (ROC) curve analyses, the functional cutoffs for anti-HBc, ALT, HBsAg, HBcrAg and HBV DNA for predicting spontaneous ESC and determining HBeAg-positive NAH termination were designated. Results Anti-HBc ≤3 lgIU/mL, ALT ≤60 U/L, HBsAg >4.602 lgIU/mL, HBcrAg >5.477 lgkU/mL and HBV DNA>7.477 lgIU/mL were designated as the functional cutoffs for identifying HBeAg-positive NAH. With criteria of the functional cutoffs, the sensitivities and specificities of low levels of anti-HBc tandem high levels of HBsAg, HBcrAg, and HBV DNA in identifying liver pathological “grade ≤G1 and stage ≤S1” were 17.6% and 94.9%, 15.7% and 96.6%, and 15.7% and 91.5%, respectively, and the positive and negative likelihood ratios of which were 3.451 and 0.868, 4.618 and 0.873, and 1.847 and 0.921, respectively; the sensitivities and specificities of low levels of ALT tandem high levels of HBsAg, HBcrAg, and HBV DNA in identifying liver pathological “grade ≤G1 and stage ≤S1” were 30.6% and 85.7%, 31.8% and 89.0%, and 34.1% and 79.1%, respectively, and the positive and negative likelihood ratios of which were 2.140 and 0.810, 2.891 and 0.766, and 1.632 and 0.833, respectively. Conclusion Low levels of anti-HBc, and ALT tandem high levels of HBsAg, HBcrAg, and HBV DNA are all effective combinations and have close capablity and similar performance in identifying HBeAg-positive NAH.

Key words: Hepatitis B core antibody, Alanine transaminase, Hepatitis B surface antigen, Hepatitis B core-related antigen, Natural history

黄丹, 陆伟, 张占卿, 李海聪, 朱召芹. 血清抗-HBc与ALT串联HBV复制标志物识别HBeAg阳性慢性HBV感染非活动性肝炎的性能[J]. 肝脏, 2025, 30(12): 1611-1619.

HUANG Dan, LU Wei, ZHANG Zhan-qing, LI Hai-cong, ZHU Zhao-qin. An evaluation on the efficacy of serum anti-HBc versus ALT tandem HBV replication markers in identifying HBeAg-positive non-aggressive hepatitis patients with chronic HBV infection[J]. Chinese Hepatolgy, 2025, 30(12): 1611-1619.

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