基于肝活检的 ALT 正常或轻度升高的慢性乙型肝炎患者 qAnti-HB

StephenW

基于肝活检的 ALT 正常或轻度升高的慢性乙型肝炎患者 qAnti-HBc 与肝脏炎症的剂量反应关系
张迟 1 , 刘奕琪 1 , 李嘉文 1 , 刘慧 2 , 陈绍 2 , 刘丹 1 , 于敏 1 , 西宏丽 1 , 赵宏 1 3 , 王贵强 1 3
隶属关系
隶属关系

    1
    北京大学第一医院肝病中心感染科，北京，100034
    2
    首都医科大学北京佑安医院病理科，北京，100069
    3
    北京大学国际医院感染科，北京，102206

    PMID：35419853 DOI：10.1002/jmv.27779

抽象的

背景：ALT（NMALT）水平正常或轻​​度升高的慢性乙型肝炎（CHB）患者中度至重度炎症的比例并不罕见。然而，我们缺乏合适的生物标志物来评估这些人群的肝脏炎症。我们旨在探讨定量乙型肝炎核心抗体（qAnti-HBc）与肝脏组织学炎症的关系。

方法：这项多中心队列研究纳入了来自中国 34 家医院的参与者，包括 1376 名接受肝活检的初治 CHB 患者（934 名接受 NMALT 的患者进入初治队列；423 名接受二次肝活检的患者进入治疗队列）。使用未调整和多变量调整的广义线性模型、具有平滑曲线拟合的广义相加模型，我们评估了这些患者的 qAnti-HBc 与肝脏炎症之间的关联。

结果：在初治患者中，qAnti-HBc与肝脏炎症呈正相关（通过Ishak评分系统评估的组织学活动指数[HAI]）（完全调整模型：β=0.48，95%CI[0.30-0.66]， P<0.001)。 qAnti-HBc每增加一个SD，中度至重度炎症（HAI≥5）的风险增加了56%（OR=1.56, 95%CI[1.28-1.91], P<0.001）。曲线拟合表明存在显着的“阈值效应”（拐点为 4.5 log10 IU/mL，P<0.001）。亚组分析和交互作用均不显着（均P>0.05）。在接受治疗的患者中，无论是基于未调整、最小调整还是完全调整的模型，qAnti-HBc与肝脏炎症之间均无显着相关性（均P>0.100）。配对分析显示 qAnti-HBc 降低与肝脏炎症缓解之间存在显着相关性。

结论：qAnti-HBc 与 NMALT 的初治 CHB 患者的肝脏炎症呈正相关。 qAnti-HBc 诊断中度至重度炎症的临界值为 4.5 log10 IU/mL。 qAnti-HBc 降低与肝脏炎症缓解呈正相关。本文受版权保护。版权所有。

关键词：慢性乙型肝炎；肝活检；肝脏炎症; ALT正常或轻度升高；定量乙型肝炎核心抗体。

本文受版权保护。版权所有。

StephenW

Dose-response relationship between qAnti-HBc and liver inflammation in chronic hepatitis B with normal or mildly elevated ALT based on liver biopsy
Chi Zhang  1 , Yiqi Liu  1 , Jiawen Li  1 , Hui Liu  2 , Chen Shao  2 , Dan Liu  1 , Min Yu  1 , Hongli Xi  1 , Hong Zhao  1   3 , Guiqiang Wang  1   3
Affiliations
Affiliations

    1
    Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, 100034, China.
    2
    Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
    3
    Department of Infectious Diseases, Peking University International Hospital, Beijing, 102206, China.

    PMID: 35419853 DOI: 10.1002/jmv.27779

Abstract

Background: The proportion of chronic hepatitis B(CHB) patients with normal or mildly elevated ALT(NMALT) levels who have moderate to severe inflammation was not rare. However, we lacked appropriate biomarkers to evaluate liver inflammation in these populations. We aimed to explore the relationship between quantitative hepatitis B core antibody(qAnti-HBc) and hepatic histological inflammation.

Method: This multi-center cohort study enrolled participants from 34 Chinese hospital including 1376 treatment-naive CHB patients with liver biopsy(934 with NMALT entered treatment-naive cohort; 423 with secondary liver biopsy entered treatment cohort). Using unadjusted and multivariate-adjusted generalized linear models, generalized additive models with smooth curve fitting, we evaluated the associations between qAnti-HBc and liver inflammation in these patients.

Results: In the treatment-naive patients, qAnti-HBc was positively associated with liver inflammation(histology activity index[HAI] evaluated by Ishak scoring system)(fully-adjusted model: β=0.48, 95%CI[0.30-0.66], P<0.001). For per-SD increase in qAnti-HBc, the risk of moderate to severe inflammation(HAI≥5) increased by 56%(OR=1.56, 95%CI[1.28-1.91], P<0.001). The curve fitting indicated a significant "threshold effect" (inflection point was 4.5 log10 IU/mL, P<0.001). Subgroup analyses and interactions were not significant(all P>0.05). In the treatment patients, there was no significant correlation between qAnti-HBc and liver inflammation, whether based on unadjusted, minimally-adjusted, or fully-adjusted models(all P>0.100). Paired analyses showed a significant correlation between decreasing in qAnti-HBc and alleviation of liver inflammation.

Conclusions: qAnti-HBc was positively correlated with liver inflammation in treatment-naive CHB patients with NMALT. The cutoff value of qAnti-HBc for the diagnosis of moderate to severe inflammation was 4.5 log10 IU/mL. Decreasing in qAnti-HBc was positively correlated with liver inflammation relieving. This article is protected by copyright. All rights reserved.

Keywords: chronic hepatitis B; liver biopsy; liver inflammation; normal or mildly elevated ALT; quantitative hepatitis B core antibody.

This article is protected by copyright. All rights reserved.