Abstract
Background: After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter. Methods: miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases. Results: LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling. Conclusions: liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.
Highlights
Since the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 (HIV-1) infection is not, anymore, an exclusion criterion for liver transplantation (LT) in patients with a Hepatitis C virus (HCV)-related end stage disease [1,2,3]
Summaryofofthe the“Gene enriched functional terms associated with the predicted target genes of miRNAs differentially expressed in Liver biopsies (LB) obtained from HCV-inwith the predicted target genes of miRNAs differentially expressed in LB obtained from HCV-infected fected patients vs. healthy livers
Among these enriched biological processes, we found once again pathways related to cell metabolism, immunity, viral process and blood coagulation, suggesting the existence of different modulatory events occurring in HCV and HCV/HIV patients (Supplementary Tables S13 and S14)
Summary
Since the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 (HIV-1) infection is not, anymore, an exclusion criterion for liver transplantation (LT) in patients with a Hepatitis C virus (HCV)-related end stage disease [1,2,3]. This latter is the consequence of chronic inflammation, immune activation, and immune senescence due to HCV infection [4,5]. Recent studies have suggested that DAAmediated HCV eradication could represent an impediment to HIV reservoir elimination in coinfected patients [4,12], and that DAA treatment does not completely normalize immune and liver functions as well as the risk of hepatocellular carcinoma development [13,14]
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