丙型肝炎病毒-人类免疫缺陷病毒合并感染患者直接作用抗病毒治疗后肝纤维化和免疫特征的长期演变。

Long-term evolution in liver fibrosis and immune profile after direct-acting antivirals therapy in hepatitis C virus-human immunodeficiency virus co-infected patients.

机构信息

HIV Unit, Hospital Clínic de Barcelona, Barcelona, Spain.

出版信息

Clin Microbiol Infect. 2022 Apr;28(4):610.e1-610.e7. doi: 10.1016/j.cmi.2021.08.019. Epub 2021 Aug 28.

DOI:10.1016/j.cmi.2021.08.019

PMID:34464735

Abstract

OBJECTIVE

Hepatitis C virus (HCV) therapy with direct-acting antivirals (DAA) achieves high rates of sustained virological response in people living with human immunodeficiency virus (HIV) (PLWH). Information on its long-term clinical impact is scarce. The aim of this study was to analyse liver fibrosis and immune response evolution after DAA treatment.

METHODS

Retrospective, single centre cohort study of HIV-HCV co-infected patients treated with DAA between June 2013 and June 2018. We analysed the changes during follow up in liver fibrosis (assessed by transient elastography (TE), aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 scores) and immunity (CD4 and CD8 cells counts and CD4/CD8 ratio).

RESULTS

We included 410 patients; 75% (308/407) men with a mean age of 50 years (SD 8); 78% (318/410) had long chronic HCV infection (median 21 years, interquartile range (IQR) 6-27 years) and 27% (107/393) had liver cirrhosis. Liver fibrosis improvement based on the decrease in TE value compared with the baseline occurred in 43% (131/302) of patients and 31% of patients based on biological scores (APRI: 124/398; FIB-4: 104/398) (p < 0.0001), being more frequent in those with advanced baseline fibrosis (83/144). The higher decrease was observed at 6 months after DAA therapy (-0.23; 95% CI -0.29 to -0.18), but a continuum in fibrosis regression of at least 30% from baseline value of TE was observed along the follow up (32% of patients at month 6, 51% at month 24 and 55% at month 48). Regarding the immunological profile, there was a significant decrease in CD8 counts at month 48 (-62.38; 95% CI -106.77 to -17.99; p 0.0001) and a progressive rise in the CD4/CD8 ratio after 24 months of follow up reaching an increment of +0.07 (95% CI 0.03-0.10, p 0.0001) at month 48.

CONCLUSIONS

HCV treatment with DAA in PLWH is associated with significant progressive improvement in liver fibrosis and recovery of the immune system with an increase in the CD4/CD8 ratio in long-term follow up.

摘要

目的

直接作用抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）在人类免疫缺陷病毒（HIV）（PLWH）感染者中实现了高持续病毒学应答率。关于其长期临床影响的信息很少。本研究旨在分析 DAA 治疗后肝纤维化和免疫反应的演变。

方法

对 2013 年 6 月至 2018 年 6 月期间接受 DAA 治疗的 HIV-HCV 合并感染患者进行回顾性、单中心队列研究。我们分析了随访期间肝纤维化（通过瞬时弹性成像（TE）、天冬氨酸氨基转移酶与血小板比值指数（APRI）和 FIB-4 评分评估）和免疫（CD4 和 CD8 细胞计数和 CD4/CD8 比值）的变化。

结果

我们纳入了 410 名患者；75%（308/407）为男性，平均年龄 50 岁（标准差 8）；78%（318/410）有长期慢性 HCV 感染（中位数 21 年，四分位距（IQR）6-27 年）和 27%（107/393）有肝硬化。与基线相比，TE 值降低的肝纤维化改善发生在 43%（131/302）的患者中，生物评分的改善发生在 31%的患者中（APRI：124/398；FIB-4：104/398）（p<0.0001），基线纤维化程度较高的患者改善更为明显（83/144）。DAA 治疗后 6 个月观察到的下降幅度最大（-0.23；95%置信区间-0.29 至-0.18），但在整个随访期间，TE 基线值至少下降 30%的纤维化持续消退（6 个月时 32%的患者，24 个月时 51%的患者，48 个月时 55%的患者）。关于免疫谱，48 个月时 CD8 计数显著下降（-62.38；95%置信区间-106.77 至-17.99；p<0.0001），并且在 24 个月的随访后 CD4/CD8 比值逐渐升高，48 个月时增加+0.07（95%置信区间 0.03-0.10，p<0.0001）。