LAUSR

ABSTRACT Human immunodeficiency virus type 1 (HIV‐1)‐induced inflammation and/or long‐term antiretroviral drug toxicity may contribute to the evolution of liver disease. We investigated circulating plasma microRNAs (miRNAs) as potential biomarkers of liver injury in patients mono‐infected with HIV‐1. We performed large‐scale deep sequencing analyses of small RNA level on plasma samples from patients with HIV‐1 mono‐infection that had elevated or normal levels of alanine aminotransferase (ALT) or focal nodular hyperplasia (FNH). Hepatitis C virus (HCV) mono‐infected patients were also studied. Compared to healthy donors, patients with HIV‐1 or HCV mono‐infections showed significantly altered (fold change >2, adjusted p < 0.05) level of 25 and 70 miRNAs, respectively. Of the 25 altered miRNAs found in patients with HIV‐1, 19 were also found in patients mono‐infected with HCV. Moreover, 13 of the 14 most up‐regulated miRNAs (range: 9.3–3.4‐fold increase) in patients with HCV mono‐infections were also up‐regulated in patients with HIV‐1 mono‐infections. Importantly, most of these miRNAs significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels, and liver fibrosis stage (p < 0.05). MiR‐122‐3p and miR‐193b‐5p were highly up‐regulated HIV‐1 mono‐infected patients with elevated ALT or FNH, but not in HIV‐1 patients with normal levels of ALT. These results reveal that HIV‐1 infections impacted liver‐related miRNA levels in the absence of an HCV co‐infection, which highlights the potential of miRNAs as biomarkers for the progression of liver injury in HIV‐1 infected patients. Graphical abstract Figure. No Caption available. HighlightsHIV‐1 infection dysregulates circulating plasma levels of liver injury‐associated microRNAs.Circulating plasma levels of liver injury‐associated miRNAs are significantly correlated with ALT and AST levels.Circulating miRNAs are potential biomarkers for the progression of liver disease and fibrosis in HIV‐1 infected individuals.