AbstractsMedical & Health Science

HIV-1/HCV co-infection; proteomics and liver fibrosis

by Carlos Melendez-Peña




Institution: McGill University
Department: Department of Medicine
Degree: PhD
Year: 2015
Keywords: Health Sciences - Medicine and Surgery
Record ID: 2058679
Full text PDF: http://digitool.library.mcgill.ca/thesisfile130344.pdf


Abstract

Hepatitis C virus (HCV) co-infection occurs in ≥ 30% of Human immunodeficiency virus type-1 (HIV-1)-infected patients in developed countries. Compared to HIV-1 alone, co-infection with HCV is associated with: increased HIV-1-related kidney problems, higher prevalence of cardiovascular disease, and increased cognitive-motor impairment. However, liver disease is by far the most serious complication of HIV-1/HCV co-infection. HCV–associated liver damage (including fibrosis, cirrhosis and end of stage liver disease (ESLD)) are all more prevalent and accelerated in HIV-1-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling error. These problems have prompted a search for non-invasive methods for liver fibrosis staging.To this end, we compared plasma proteome profiles at different stages of fibrosis in HCV mono and HIV-1/HCV co-infected patients using surface-enhanced laser desorption ionization-time-of-flight mass spectrometry (SELDI-TOF MS). This technology offers high-throughput protein profiling of native biological specimens. Using SELDI-TOF MS to develop algorithms for the staging of liver fibrosis in HIV-1/HCV co-infected individuals, we were able to identify serum apolipoprotein A1, haptoglobin and plasminogen as candidate biomarkers for liver fibrosis. In the course of this work, we observed an important heterogeneity in the plasma proteome of co-infected patients. In particular, we were interested in fibrosis progression rates in HIV-1/HCV co-infected patients as assessed by the aspartate aminotransferase (AST)-to-platelet-ratio index (APRI) according to the sequence of infection with both viruses. We have shown that the sequence of infection has no effect on the percentage of patients who will eventually develop liver fibrosis but that those who are infected with HIV-1 first will progress to liver fibrosis at an accelerated rate. Dans les pays développés, la co-infection avec le virus de l'hépatite C (HCV) se produit dans ≥ 30% des patients infectés par le virus d'immunodéficience humain type-1 (VIH-1). Comparé au VIH-1 seul, la co-infection avec HCV est associée avec une augmentation des problèmes rénaux, une plus grande prévalence des maladies cardiovasculaires et une augmentation des problèmes moteur-cognitifs. Par contre, la complication la plus importante reste les maladies du foie dans les cas de co-infection au VIH-1/HCV. Les problèmes du foie reliés au HCV (incluant la fibrose, la cirrhose et maladies du foie en phase terminal) sont plus répandus et accélérés chez les individus infectés par le VIH-1. Même si la biopsie du foie reste le test standard pour déterminer le niveau de fibrose du foie associé avec le HCV, ce test peut causer des complications et être assujetti à des erreurs d'échantillonnage. De ce fait, la recherche pour des méthodes non-invasives pour évaluer le niveau de fibroses du foie demeure nécessaire. À cette fin, nous avons comparé le profile…