儿童时期的乙型肝炎病毒表面抗原滴度基线可预测成年后发生晚期肝纤维化的风险。

Baseline Hepatitis B Virus Surface Antigen Titers in Childhood Predict the Risk of Advanced Liver Fibrosis in Adulthood.

机构信息

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Clin Gastroenterol Hepatol. 2023 Mar;21(3):663-669.e1. doi: 10.1016/j.cgh.2022.02.046. Epub 2022 Feb 28.

DOI:10.1016/j.cgh.2022.02.046

PMID:35240329

Abstract

BACKGROUND & AIMS: Hepatitis B virus (HBV) surface antigen (HBsAg) is a marker of both HBV covalently closed circular DNA and integrated HBV genome, whereas the HBV core-related antigen (HBcrAg) indicates the transcriptional activity of covalently closed circular DNA. This study examined the relationship between HBsAg and HBcrAg titers in childhood and advanced fibrosis in adulthood.

METHODS

We recruited 214 initially hepatitis B e antigen-positive chronic HBV-infected patients who were followed for a total of 6371 person-years. None of the patients were co-infected with hepatitis C or D virus. Serum HBsAg and HBcrAg titers were assessed at 10 and 15 years of age. Transient elastography was performed at a mean final age of 38.21 years to identify advanced fibrosis.

RESULTS

Patients with advanced fibrosis in adulthood had a higher rate of genotype C HBV infection and a higher HBsAg titer at 10 and 15 years of age (P = .003, P = .03, and P = .005, respectively). The HBcrAg titer was not correlated with advanced fibrosis (P > .05). Receiver operating characteristic curve analysis showed that HBsAg cutoffs of >4.23 and >4.44 log IU/mL at 10 and 15 years of age, respectively, best predicted advanced fibrosis in the fourth decade of life (P = .001 and P < .001, respectively). In a multivariate analysis, both an HBsAg titer >4.44 log IU/mL at 15 years of age and HBV genotype C were predictors of advanced fibrosis (odds ratios, 15.43 and 4.77; P = .01 and P = .02, respectively).

CONCLUSIONS

HBsAg titers in childhood predict the progression to liver fibrosis in adulthood.

摘要

背景与目的

乙型肝炎病毒（HBV）表面抗原（HBsAg）既是 HBV 共价闭合环状 DNA 也是整合 HBV 基因组的标志物，而 HBV 核心相关抗原（HBcrAg）则表明共价闭合环状 DNA 的转录活性。本研究旨在检测儿童时期 HBsAg 和 HBcrAg 滴度与成年期进展性肝纤维化之间的关系。

方法

我们招募了 214 例最初为乙型肝炎 e 抗原阳性的慢性 HBV 感染者，这些患者总共随访了 6371 人年。所有患者均未合并感染丙型或丁型肝炎病毒。在 10 岁和 15 岁时检测血清 HBsAg 和 HBcrAg 滴度。在平均最终年龄为 38.21 岁时进行瞬时弹性成像，以确定是否存在进展性纤维化。

结果

成年期存在进展性纤维化的患者中，乙型肝炎病毒基因型 C 感染率更高，10 岁和 15 岁时 HBsAg 滴度也更高（P =.003、P =.03 和 P =.005）。HBcrAg 滴度与进展性纤维化无关（P >.05）。受试者工作特征曲线分析显示，10 岁和 15 岁时 HBsAg 分别>4.23 和>4.44 log IU/mL 的切点值可最好预测 40 岁时的进展性纤维化（P =.001 和 P <.001）。多变量分析显示，15 岁时 HBsAg 滴度>4.44 log IU/mL 和乙型肝炎病毒基因型 C 是进展性纤维化的预测因素（比值比，15.43 和 4.77；P =.01 和 P =.02）。