ABSTRACT
Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52-66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4â%), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1ß were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.
Subject(s)
Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Interferon-alpha/therapeutic use , Leukocytes, Mononuclear/virology , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , Chemokine CCL4/genetics , Drug Therapy, Combination , Female , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Interleukin-12 Subunit p35/genetics , Interleukin-6/genetics , Interleukin-8/genetics , Leukocytes, Mononuclear/immunology , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/genetics , Recombinant Proteins/therapeutic use , Treatment Outcome , Tumor Necrosis Factor-alpha/genetics , Viral Load , Viral Nonstructural Proteins/geneticsABSTRACT
AIM: The aim of this study was to evaluate prevalence of hepatitis C virus (HCV) harbouring mutations associated with decreased susceptibility to protease inhibitors (Boceprevir/Telaprevir) among Polish untreated patients infected with HCV genotype 1. MATERIAL AND METHOD: Population sequencing was used, sequencing data were interpreted by web based geno2pheno algorithm. A total of 91 serum samples were obtained from patients infected with HCV genotype 1, admitting Outpatient Clinics of Hospital of Infectious Diseases, Warsaw. RESULTS: Sequencing analysis of the NS3 protease catalytic domain was successful in 85 out of 91 subjects. In seventy three (85.9%) out of 85 samples wild-type HCV was detected; in 12 (14.1%) samples mutations associated with clinically observed Boceprevir/Telaprevir-decreased susceptibility were detected. SUMMARY AND CONCLUSIONS: Obtained results document the presence of HCV strains harbouring protease inhibitors (PIs) resistance-associated mutations among Polish therapy-naïve patients. The determined prevalence of drug resistant HCV variants is 14.1%. Further and continuous surveillance is necessary to estimate how preexisting and emerging drug resistance mutations influence clinical outcome in triple-therapy experienced patients.