Abstract
Chronic liver disease is becoming a leading cause of illness and mortality in patients living with human immunodeficiency virus (HIV; PLWH) undergoing suppressive anti-retroviral therapy. Its primary etiology is coinfection with hepatitis B and C virus (HBV and HCV, respectively). Chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore plasma protein profiles of PLWH and those coinfected with HBV and HCV using shotgun proteomics. HIV-monoinfected, HIV/HBV-coinfected, HIV/HCV-coinfected and uninfected control individuals were recruited. Patients in the three virus-infected groups had significantly higher levels of liver fibrosis indices (fibrosis-4 score and aspartate aminotransferase to platelet ratio index) compared with the control group. Liquid chromatography-tandem mass spectrometry analysis of plasma samples identified 1,074 proteins that were differentially expressed, where subsequent partial least squares-discriminant analysis model demonstrated clear clustering of proteomes from the four sample groups; 18 proteins that were significantly differentially expressed. Heatmap analysis identified two main groups of proteins, six proteins being upregulated only in the HIV/HBV-coinfection group and 10 proteins downregulated in all three virally infected groups. STITCH 5.0 analysis predicted an interaction network containing two identified proteins in the latter group, specifically ubiquitin interaction motif-containing 1 (UIMC1) and haptoglobin (HP), which are part of the profibrogenic TGF-1β/SMAD, inflammatory TNF and tumor suppressor BRCA1 pathways. Expression levels of UIMC1 and HP were significantly lower in HIV-infected groups compared with those in uninfected controls. Altogether, these proteomics data provide protein expression profiles potentially associated with HIV infection and coinfection with HBV/HCV, which may be applied to predict progression to advanced liver disease or HCC in PLWH.