Nucleos（t）ide类似疗法在慢性乙型肝炎患者中的纵向效应和治

StephenW

Antiviral Res. 2019 May 21. pii: S0166-3542(19)30048-8. doi: 10.1016/j.antiviral.2019.05.007. [Epub ahead of print]
Longitudinal effects of Nucleos(t)ide analogue therapy in chronic hepatitis B patients and the utility of non-invasive fibrosis markers during treatment: A single-center experience for up to 17 years.
Surana P1, Kapuria D1, Broadwell C1, Wright EC2, Takyar V1, Kleiner DE3, Ghany MG1, Ben-Yakov G1, Heller T1, Liang TJ1, Koh C4.
Author information

1
    Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
2
    Office of the Director, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
3
    Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
4
    Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: [email protected].

Abstract
BACKGROUND:

Fibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated.
AIMS:

To characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients.
METHODS:

Histology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naïve CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally.
RESULTS:

80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4-6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03).
CONCLUSION:

Early dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment.

Copyright © 2019. Published by Elsevier B.V.
KEYWORDS:

Fibrosis; Hepatitis B; Inflammation; Non-invasive markers of fibrosis; Nucleoside analogues

PMID:
    31125632
DOI:
    10.1016/j.antiviral.2019.05.007

StephenW

抗病毒药物2019年5月21日.pii：S0166-3542（19）30048-8。 doi：10.1016 / j.antiviral.2019.05.007。 [印刷前的电子版]
Nucleos（t）ide类似疗法在慢性乙型肝炎患者中的纵向效应和治疗期间非侵入性纤维化标志物的效用：单中心体验长达17年。
Surana P1，Kapuria D1，Broadwell C1，Wright EC2，Takyar V1，Kleiner DE3，Ghany MG1，Ben-Yakov G1，Heller T1，Liang TJ1，Koh C4。
作者信息

1
    美国国立卫生研究院国家糖尿病与消化和肾脏疾病研究所肝病科，美国马里兰州贝塞斯达市。
2
    美国马里兰州贝塞斯达国立卫生研究院国家糖尿病与消化和肾脏疾病研究所所长办公室。
3
    美国国立卫生研究院国家癌症研究所病理学实验室，美国马里兰州贝塞斯达。
4
    美国国立卫生研究院国家糖尿病与消化和肾脏疾病研究所肝病科，美国马里兰州贝塞斯达市。电子地址：[email protected]。

抽象
背景：

纤维化退化与慢性乙型肝炎（CHB）患者的核苷类似物（NA）治疗有关。虽然已经在CHB中评估了非侵入性纤维化标志物，但是尚未评估它们用于监测治疗组织学回归的效用。
目的：

表征疾病严重程度的改善和非侵入性生物标志物在CHB NA治疗患者中的效用。
方法：

在基线和纵向评估来自未治疗的CHB患者的组织学，实验室，AST-血小板比率指数和Fibrosis-4（Fib-4）。评估治疗期间从基线到不同时间点的相对变化。纵向进行APRI和Fib-4与组织学的相关分析。
结果：

研究了80例CHB患者（84％男性，中位年龄45岁（IQR 32,54））组织学长达17年（中位数6（IQR 3.9,8.0））年。中位基线Ishak纤维化为3（IQR 2,4），组织学活动指数（HAI）炎症为9（IQR 7,11），用于检测肝硬化的纤维化标志物AUROC（Ishak≥5）> .64。 HAI在第1年提高了54％，在第2年提高了37％，均高于其余的随访期。在第一年内，纤维化改善了35％，超过所有其他时间段。非侵入性生物标志物开始与组织学相关超过4年（APRI：4-6岁：r = 0.33，p = 0.03;≥6年：r = 0.41，p = 0.009; Fib-4：≥6年：r = 0.35，p = 0.03）。
结论：

组织学的早期动态变化发生在NA患者的CHB患者中，然后进行线性改善。非侵入性纤维化生物标志物不能捕获这些动态变化，并且可以证明超过4年治疗的临床效用。

版权所有©2019。Elsevier B.V.
关键词：

纤维化;乙型肝炎;炎;纤维化的非侵入性标志物;核苷类似物

结论：
    31125632
DOI：