Reinfection of Transplanted Livers in HCV- and HCV/HIV-Infected Patients Is Characterized by a Different MicroRNA Expression Profile

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.

Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co‐infection: A nationwide survey in Japan

“…25 Recently, it has been reported that DAA treatment is very effective for patients co-infected with HCV/HCV before and after LT in Germany. 26 In the report, it was shown that various DAAs were effective and achieved an SVR-12.…”

The involvement of microRNAs in HCV and HIV infection

“…These liver samples were affected by HCV but had not yet undergone any severe liver injury like cirrhosis but associated with the processes of viral reinfection, neurologic impairment, and coagulation disorders. 111 , 112 Researchers believed this approach might become helpful in identifying different miRNAs that play a role in the early stage of disease progression. 111 , 112 Results so far claimed miR29b, miR-200c, miR-222, and miR-338-3p can possibly act as biomarkers.…”

“… 111 , 112 Researchers believed this approach might become helpful in identifying different miRNAs that play a role in the early stage of disease progression. 111 , 112 Results so far claimed miR29b, miR-200c, miR-222, and miR-338-3p can possibly act as biomarkers. Upregulation of miR-200c after transplantation can represent increased chances of reinfection, while downregulation of miR-338-3p signifies a lack of tumor-suppressing activities.…”

“… 111 In addition, it was stated that the dysregulation of miR-29b and miR-222 might play the important role in impairing the immune response favoring fibrosis in HCV/HIV co-infected patients. 112 …”

“…111 In addition, it was stated that the dysregulation of miR-29b and miR-222 might play the important role in impairing the immune response favoring fibrosis in HCV/HIV co-infected patients. 112 Likewise, many different microRNAs are identified as potential biomarkers in liver disease progression representing different pathways/ mechanisms. 113 One such is miR-101 which in normal conditions is indulged in prohibiting hepatic stellate cells activation and pro-fibrogenic cytokines release via TGF-β inhibition.…”