摘要
乙型肝炎病毒(hepatitis B virus, HBV) e抗原(hepatitis B e antigen, HBeAg)阳性的慢性HBV感染依次经历非活动性肝炎(non-aggressive hepatitis, NAH)和活动性肝炎(aggressive hepatitis, AH)2个分期,但仍缺乏界定HBeAg阳性NAH与AH的可靠标准。本文根据179例患者的长期随访队列,以自发性HBeAg血清转换作为终点事件,采用Kaplan-Meier生存分析,指定了丙氨酸转氨酶(alanine transaminase, ALT)、HBV表面抗原(hepatitis B surface antigen, HBsAg)和HBV DNA识别HBeAg阳性NAH的功能截断值;在此基础上,评价了ALT串联HBsAg和串联HBV DNA识别HBeAg阳性NAH的性能。结果显示,ALT≤60 IU/L、HBsAg >4.602 log10 IU/mL和HBV DNA >7.477 log10 IU/mL为识别HBeAg阳性NAH的功能截断值。基于功能截断值,ALT串联HBsAg的患者中,病理学分级≤G1和“分级≤G1且分期≤S2”的构成比均为100%,病理学分期≤S1和“分级≤G2且分期≤S1”的构成比均为68.2%;ALT串联HBV DNA的患者中,病理学分级≤G1和“分级≤G1且分期≤S2”的构成比均为86.2%,病理学分期≤S1和“分级≤G2且分期≤S1”的构成比均为69.0%;ALT串联HBsAg识别病理学分级≤G1和“分级≤G1且分期≤S2”的阳性似然比均为+∞,识别病理学分期≤S1和“分级≤G2且分期≤S1”的阳性似然比均为2.034;ALT串联HBV DNA识别病理学分级≤G1和“分级≤G1且分期≤S2”的阳性似然比分别为3.000和3.068,识别病理学分期≤S1和“分级≤G2且分期≤S1”的阳性似然比均为2.106。以上结果提示,ALT串联HBsAg和串联HBV DNA均可有效识别HBeAg阳性NAH;且ALT串联HBsAg识别HBeAg阳性NAH的性能优于ALT串联HBV DNA。
Abstract
Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection undergoes two phases in sequence, termed non-aggressive hepatitis (NAH) and aggressive hepatitis (AH), respectively. But there is still a lack of perfect standard for defining HBeAg-positive NAH and AH. In this study, based on a long-term follow-up cohort of 179 patients, the functional cutoffs for alanine transaminase (ALT), hepatitis B surface antigen (HBsAg) and HBV DNA in identifying HBeAg-positive NAH were designated using Kaplan-Meier survival analysis with spontaneous HBeAg seroconversion as the endpoint event; On this basis, the performance of ALT in tandem with HBsAg and in tandem with HBV DNA in identifying HBeAg-positive NAH was evaluated. The results showed that, ALT≤60 IU/L, HBsAg >4.602 log10 IU/mL and HBV DNA >7.477 log10 IU/mL were the functional cutoffs in identifying HBeAg-positive NAH. Based on the functional cutoffs, among patients with ALT in tandem with HBsAg, the proportion of patients with pathological grade≤G1 and “grade≤G1 and stage≤S2” were both 100%, and with pathological stage≤S1 and “grade≤G2 and stage≤S1” were both 68.2%; among patients with ALT in tandem with HBV DNA, the proportion of patients with pathological grade≤G1 and “grade≤G1 and stage≤S2” were both 86.2%, and with pathological stage≤S1 and “grade≤G2 and stage≤S1” were both 69.0%; the positive likelihood ratios of ALT in tandem with HBsAg in identifying pathological grade≤G1 and “grade≤G1 and stage≤S2” were both +∞, and in identifying pathological stage≤S1 and “grade≤G2 and stage≤S1” were both 2.034; the positive likelihood ratios of ALT in tandem with HBV DNA in identifying pathological grade≤G1 and “grade≤G1 and stage≤S2” were 3.000 and 3.068, respectively, and in identifying pathological stage≤S1 and “grade≤G2 and stage≤S1” were both 2.106. The results suggested that, both ALT in tandem with HBsAg and in tandem with HBV DNA can effectively identify HBeAg-positive NAH. The performance of ALT in tandem with HBsAg in identifying HBeAg-positive NAH is better than that of ALT in tandem with HBV DNA.
关键词
乙型肝炎病毒DNA /
HBV表面抗原 /
慢性乙型肝炎 /
自然史 /
生存分析
Key words
Hepatitis B virus DNA /
Hepatitis B surface antigen /
Chronic hepatitis B /
Natural history /
Survival analysis
黄丹1,陆伟1,张占卿1,李海聪2,朱召芹2.
血清ALT串联HBsAg和串联HBV DNA识别HBeAg阳性慢性HBV感染非活动性肝炎的性能评价[J]. 微生物与感染. 2024, 19(1): 12-26 https://doi.org/10.3969/j.issn.1673-6184.2024.01.002
HUANG Dan1, LU Wei1, ZHANG Zhanqing1, LI Haicong2, ZHU Zhaoqin2.
Performance evaluation of serum ALT in tandem with HBsAg and in tandem with HBV DNA in identifying HBeAg-positive chronic non-aggressive hepatitis[J]. Journal of Microbes and Infections. 2024, 19(1): 12-26 https://doi.org/10.3969/j.issn.1673-6184.2024.01.002
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基金
国家“十二五”科技重大专项(2013ZX10002005);国家“十三五”科技重大专项(2017ZX10203202);复旦大学附属公共卫生临床中心科研项目(KY-GW-2023-30)