Detection of Y93H RAV by direct sequencing at baseline and during SMV/PR therapy.

<p>BT, breakthrough;</p><p>SVR, sustained virological response</p><p>*within 7 days of the initiation of treatment, when HCV RNA was still detectable,</p><p>**at least 3 months after the end of treatment</p><p>Detection of Y93H RAV by direct sequencing at baseline and during SMV/PR therapy.</p

HCV RNA reduction of Y93H RAV versus the Y93 wild type during SMV/PR therapy.

<p>Reduction of HCV RNA from baseline to an early time point during SMV/PR therapy was determined for Y93H RAV and the Y93 wild type. Within 7 days of the initiation of therapy, HCV RNA reduction was significantly greater for Y93H RAV (-3.7 ± 1.3 logIU/mL/day) than the Y93 wild type (-3.4 ± 1.0 logIU/mL/day) (p<0.001).</p

Changes in the proportion of Y93H RAV within each individual.

<p>The proportion of Y93H RAV over the Y93 wild type within each patient was determined by deep sequencing at baseline and at an early time point during SMV/PR therapy (within 7 days). The mean proportion of Y93H RAV was 52.7% at baseline and 29.7% during therapy (p = 0.023). The proportion of Y93H was reduced in 21 of 29 cases (72.4%, solid lines). In contrast, Y93H percentages increased in 8 cases (27.6%, broken lines).</p

Changes in the proportion of Y93H RAV in 4cases with breakthrough or relapse.

<p>Deep sequencing was performed in 4 patients with relapse (a) or breakthrough (b, c, d) to quantify the proportion of Y93H RAV against the Y93 wild type. In two cases, PR therapy was continued up to 24 wks after stopping SMV (b and c). The proportion of Y93H RAV decreased during SMV/PR therapy and at the time of breakthrough/relapse compared to baseline but recovered to the baseline level at follow up. PR therapy; pegylated interferon plus ribavirin therapy, SMV/PR therapy; Simeprevir plus pegylated interferon / ribavirin therapy</p

Baseline characteristics.

<p>AST, aspartate aminotransferase’</p><p>ALT, alanine aminotransferase’</p><p>AFP, alpha-fetoprotein’</p><p>PR therapy, pegylated interferon plus ribavirin therapy’</p><p>RAV, resistance-associated variants’</p><p>SMV/PR therapy; Simeprevir plus pegylated interferon / ribavirin therapy’</p><p>TVR, telaprevir,</p><p>SVR; sustained virological response</p><p>Baseline characteristics.</p

Factors associated with rapid fibrosis progression.

<p>Factors associated with rapid fibrosis progression.</p

Changes of fibrosis stage over time.

<p>Progression of fibrosis was defined as a 1 point or more increase in the METAVIR score. Regression of fibrosis was defined as 1 point or more decrease in the METAVIR score.</p

Association of SNPs genotype with fibrosis progression rate.

<p>Error bars indicate the standard error.</p

Patients characteristics at baseline.

<p>Patients characteristics at baseline.</p

Association between fibrosis progression rate and combining risk analysis (FPR score).

<p><i>IL28B</i> TG/GG, <i>PNPLA3</i> CG/GG, and average ALT after interferon therapy ≥ 40 IU/l were scored as 1 point. Similarly, <i>IL28B</i> TT, <i>PNPLA3</i> CC, and average ALT after interferon therapy < 40 IU/l were scored as 0 point. Patients scored 0–1, 2 and 3 were defined as a low, intermediate, and high risk group, respectively. Error bars indicate the standard error.</p