Materials and Methods: Five naïve HCV pts (GT4d, GT4a, GT4o n=3,1,1) from the Command 4 Study, candidates for pIFN/RBV+DCV treatment were considered. Plasma samples were collected at baseline and during therapy. The presence and frequency of HCV variants within the NS5A quasispecies was analyzed by ultra-deep pyrosequencing (UDPS). Results: Pt1 received pIFN/RBV, Pts2, 3 and 4 pIFN/RBV+DCV; Pt5 was a screening failure. Pt1 was relapser; Pt2 experienced breakthrough at Wk 4; Pts 3 and 4 showed sustained virological response

(SVR), with Epacadostat cell line HCV RNA undetectable since Wk 4. Considering viremic time points for Pts1 and 2, the extent of NS5A diversity was not significantly related to viral GPCR Compound Library cell assay load (r=−0.4, p=0.75 and r=−0.80, p=0.33, respectively). No substitutions were detected at positions related to DCV resistance at T0, with the exception of P58T in Pt3 (SVR). In Pt2 (breakthrough) multiple substitutions at positions 28, 31 and 93, linked to DCV resistance, were observed since Wk 4, with different kinetics (Table). Mutations were frequently associated on the same haplotype (L28S + M31I = 57, 85 and 99% at Wks4, 8 and 9; L28S + M31I + Y93H = 13, 6 and <0.6% at Wks4, 8 and 9). Conclusions: Our data

suggest that GT4d resistance patterns may involve the same amino acid residues described in GT1 and GT4a, although the substitution at position 28 is novel (L28S); UDPS allows establishing the dynamics and early appearance of substitutions potentially associated with antiviral resistance in patients undergoing DCV-based therapy. The dynamics of Y93H in GT4 patients is consistent with previous findings for GT1b patients, showing that it tends to be associated with other mutations; this suggests that this website it may not confer strong selection advantage in DCV-treated patients, as compared to L28S and M31I, which become predominant during virological failure in this study. Dynamics of mutations along treatment in Pt2 (% of quasispecies) Disclosures: Fiona McPhee – Employment: Bristol-Myers Squibb Eric A. Hughes – Employment: Bristol-Myers

Squibb The following people have nothing to disclose: Barbara Bartolini, Raffaella Lionetti, Emanuela Giombini, Chiara Taibi, Marzia Montalbano, Gianpiero D’Offizi, Giuseppe Ippolito, Anna Rosa Garbuglia, Maria R. Capobianchi Background and Aims: The associations between genetic polymorphism in patatin-like phospholipase family 3 protein (PNPLA3) gene and steatosis or fibrosis in chronic hepatitis C have been reported with conflicting results. On the other hand, data regarding the role of PNPLA3 in chronic hepatitis B is scarce. The aim of the present study was to investigate the role of the PNPLA3 genetic polymorphism in chronic hepatitis C and hepatitis B in terms of steatosis, fibrosis and the development of HCC.