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Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

ABSTRACT: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients.This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE).83% were male with a median age of 45, while 131 were co-infected with viral hepatitis. Overall, 18% had significant fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were independently associated with significant fibrosis, while HCV (OR:5.8), exposure to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below 40copies/mL (OR:0.4) was independently associated with significant fibrosis, and didanosine (OR:20.8) with cirrhosis.In conclusion, history of exposure to didanosine and azidothymidine continues to have an impact on the presence of liver cirrhosis in HIV patients. However, HCV co-infection and ongoing HIV-replication have the strongest effect on development of significant fibrosis in these patients.

SUBMITTER: Anadol E

PROVIDER: S-EPMC5773180 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

Anadol Evrim E Lust Kristina K Boesecke Christoph C Schwarze-Zander Carolynne C Mohr Raphael R Wasmuth Jan-Christian JC Rockstroh Jürgen Kurt JK Trebicka Jonel J

PloS one 20180118 1

<h4>Introduction</h4>Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients.<h4>Methods</h4>This observational cross-sectional singl ...[more]

PMID: 29346443

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Project description:AimTo investigate the relationships among diverse metalloproteases (MMPs) and their tissue inhibitors (TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus (HIV)-infected patients.MethodsSingle nucleotide polymorphisms (SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus (HCV) coinfection. A total of 158 patients were included, 57 of whom were HCV-coinfected. All patients drank < 50 g ethanol/day. Diverse SNPs (MMP-1 -1607 1G/2G, MMP-8 -799C/T, MMP-9 -1562 C/T, MMP-13 -77A/G, TNF-α -308 G/A, CCR5-∆32), and serum levels of MMPs (2, 3, 8, 9 and 10) and TIMPs (1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis (F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kPa.ResultsA total of 34 patients (21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2 (P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values (P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements (P = 0.01). Multivariate analyses showed that high levels of MMP-2 (OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2 (OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender (OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.ConclusionCertain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIV-infected patients with/without HCV coinfection.

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Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

Publications

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

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