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一组年轻的HIV感染者及HIV/HBV合并感染者的肝纤维化进展:一项使用非侵入性APRI和Fib-4评分的纵向研究。

Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores.

作者信息

Iacob Diana Gabriela, Luminos Monica, Benea Otilia Elisabeta, Tudor Ana-Maria, Olariu Cristina Mihaela, Iacob Simona Alexandra, Ruta Simona

机构信息

Department of Infectious Diseases, Emergency University Hospital, Bucharest, Romania.

Department of Infectious Diseases and Virology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

出版信息

Front Med (Lausanne). 2022 Jul 29;9:888050. doi: 10.3389/fmed.2022.888050. eCollection 2022.

Abstract

BACKGROUND

The risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance.

METHODS

We performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time.

RESULTS

During a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis.

CONCLUSIONS

The study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.

摘要

背景

即使接受抗逆转录病毒治疗(ART),HIV感染者及HIV-HBV合并感染者发生肝纤维化的风险仍会随时间增加,因此需要进行严格且定期的监测。鉴于瞬时弹性成像技术的可及性较低,我们旨在评估在HIV单感染、HIV-HBV合并感染以及HBsAg血清学清除的个体中,两种非侵入性肝纤维化评分(APRI和Fib-4)的纵向变化情况。

方法

我们在2013年至2019年间对212例HIV患者进行了一项观察性回顾性研究,其中包括111例HIV单感染个体、62例HIV-HBV合并感染且HBsAg阳性个体以及39例HIV-HBV感染且HBsAg消失个体。对这些组进行36、48和60个月的随访。肝纤维化通过APRI>0.5或Fib-4≥1.45评分来表示,进展性肝纤维化通过APRI评分>1.5或Fib-4>3.25来表示。使用广义估计方程(GEE)的逻辑回归来评估随时间发生肝纤维化的预测因素。

结果

在中位随访58.5个月期间,所有患者中肝纤维化的患病率以APRI评分计算增加了0.5%,达到11.3%;以Fib-4评分计算增加了0.9%,达到10.8%。在对应60个月的访视中,所有HIV-HBV患者的肝纤维化患病率均高于HIV单感染个体,具体如下:HIV-HBV/HBsAg阳性个体中,APRI评分为16.1%,Fib-4评分为12.9%;HIV-HBV/HBsAg阴性个体中,APRI和Fib-4评分均为12.8%;而HIV单感染个体中分别为8.1%和9%。在研究期间,肝纤维化的存在与血浆HIV RNA、CD4+T细胞计数、HIV-HBV合并感染(对于APRI>0.5)以及ART治疗依从性差(对于Fib-4>1.45)独立相关。在最后一次访视时,ART治疗依从性差和CD4+T细胞计数仍与肝纤维化相关。

结论

该研究发现,在接受广泛ART治疗的年轻HIV感染者中,APRI和Fib-4评分随时间进展缓慢。HIV单感染患者的肝纤维化评分持续增加,但无论HBsAg是否存在,均低于HIV-HBV合并感染患者。长期使用非侵入性评分进行定期随访有助于改善低收入环境下的监测,对于高分患者应采用额外的诊断方法。

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