Baseline characteristics of patients are summarized in Table 1. In the majority of patients (n = 22, 78.6%), HCV recurred within the first postoperative year. Liver
biopsies were taken twice: at the time when HCV recurrence was observed following RG-7388 purchase liver transplantation and after the end of antiviral therapy. Normal liver samples (n = 13) were obtained from deceased donors during organ receiving, just before ligation of the abdominal aorta and reperfusion. These donor livers were used for transplantation before the start of this project. Liver samples were fixed in 10% buffered formalin and embedded in paraffin. HAI (histology activity index, modified ISHAK score /0–18/) and fibrosis score /0–6/ were determined for Deforolimus molecular weight histological grading and staging of liver specimens. The study followed the ethical guidelines of the 1975 Declaration of Helsinki. Informed consent was obtained from all patients included in the study. All selected patients received the combination of IFN/RBV for 12 months without interruption. Patients with good renal function received pegylated IFN 2b, while patients with impaired renal function were treated with pegylated
IFN 2a. No additional treatment was applied. Six patients (21%) achieved sustained viral response (SVR: HCV was undetectable in the sera using reverse transcription–polymerase chain reaction [RT-PCR] 6 months following the completion of IFN/RBV therapy). Patients were defined as being non-responders (NR) if their sera were positive for HCV RNA (22 patients). All patients had HCV genotype 1b infection. There were
no significant differences in patient gender or age between the NR and SVR groups. In silico identification of miRs that may bind to any mRNAs of HCV receptors CLDN1, OCLN, SCARB1, and CD81 was performed using microRNA.org (http://www.microrna.org) target prediction database and software application developed by Tömböl and coworkers.[19] The latter is capable of merging three target prediction databases such as TargetScan 6.0 (http://www.targetscan.org), PicTar (http://pictar.mdc-berlin.de), Sodium butyrate and MicroCosm Targets Version 5 (http://www.ebi.ac.uk/enright-srv/microcosm/htdocs/targets/v5/). The database search resulted in about 550 specific miRs, from which there were 39 (CLDN1), 13 (OCLN), 1 (miR-194; CD81), and 8 (SCARB1) miRs commonly present in the database lists for the four mRNAs, respectively. Finally, the microRNA lists were narrowed down by either selecting the consensus sequences of all three databases or the sequences possibly targeting several mRNAs of different HCV receptor types, or mRNAs connected to HCV hepatitis according to the literature.