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Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

ABSTRACT: AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p?=?0.01; week 2: p?=?0.038; week 4: p?=?0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p?=?0.012; SVR: 63.6% versus 13 26.5%, p?=?0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p?=?0.01; week 4: p?=?0.02), RVR (p?=?0.015) and SVR (p?=?0.029) than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

SUBMITTER: Rivero-Juarez A

PROVIDER: S-EPMC3629002 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

Rivero-Juarez Antonio A Gonzalez Rafael R Camacho Angela A Manzanares-Martin Barbara B Caruz Antonio A Martinez-Peinado Antonio A Torre-Cisneros Julian J Pineda Juan A JA Peña José J Rivero Antonio A

PloS one 20130416 4

<h4>Aim</h4>To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients.<h4>Methods</h4>HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (R ...[more]

PMID: 23613999

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Project description:BackgroundWhether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI.MethodsSubjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed.ResultsOCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment.ConclusionsHCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.

Dataset Information

Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

Publications

Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

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