1149 PRESENCE OF VIRALLY MODIFIED LIPOPROTEINS IN HCV INFECTED PLASMA

Abstract

particles in cells co-infected with the wild-type virus. In this study, we examined the relationship between the presence of deletion mutants in the serum of HCV-infected individuals and the patient clinical characteristics or the outcome of PEG-Interferon and ribavirin (PEG-IFN/RBV) combination therapy. Methods: Study subjects were 132 individuals, chronically infected with genotype 1 HCV, who were treated with the PEG-IFN plus RBV combination therapy between September 2001 and April 2006 at the Liver Center, Ospedale Maggiore, Milan (Italy). In order to identify the defective genomes, RNA was extracted from the serum samples obtained prior to treatment. HCVRNA was amplified by long-range RT-PCR. The obtained amplicons were subsequently cloned and sequenced in order to confirm the identity of the defective viral genomes. Results: We identified HCV defective genomes in the serum of an unexpectedly high fraction of genotype 1 hepatitis C chronic patients (25/132, 19%). The presence of HCV deleted genomes was found to be associated with higher viremic levels (P = 0.04) and with hepatic necro-inflammatory activity (histologic activity index ≥9; P = 0.005) but not with the IL28B host genotype. In this cohort, we did not detect a significance association between the presence of HCV defective genomes and treatment failure. Strikingly, however, among 74 patients who were HCVRNA(−) at the end of PEG-IFN/RBV therapy, virological relapse was observed in 60% (9/15) of the patients carrying HCV with defective genomes compared to 30% (18/59) of the patients infected with only the full-length virus. Conclusions: We found that, in chronic hepatitis C patients, the presence of HCV with defective genomes was associated with higher viremia and with hepatic necro-inflammatory lesions. Furthermore, the presence of defective HCVRNA may represent a novel predictor of relapse after initial virological response following PEG-IFN/RBV combination therapy.