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Responders, relapsers had significantly higher rates of EOTVR (95.2 vs. 50.0 , P = 0.03) and SVR (78.6 vs. 0 , P = 0.004) and a lower relapse rate (17.5 vs. 100 , P = 0.04). As shown in table 2, neither any baseline factor including host IL-28B genotype nor previous virological response was significantly associated with a higher RVR rate. Lower baseline HCV RNA levels, previous virological relapse and the achievement of a RVR and an EVR were factors that were significantly associated with an SVR in the univariate analysis (table 2). Multivariate analysis revealed that the onlyAssessment of efficacyA rapid virological response (RVR) was defined as seronegativity of HCV RNA at week 4 of treatment. An EVR was defined as a seronegative or at least a 2-log10 decrease from baseline in the serum HCV RNA at week 12 of treatment. An end-of-treatment virological response (EOTVR) was defined as seronegativity of HCV RNA at the end of treatment. The endpoint of the study was the achievement of a sustained virological response (SVR), whichHCV-2 RetreatmentTable 1. Basic demographic, virological, and clinical features of HCV genotype 2 Epigenetics patients who failed interferon-based therapy.All patients (N = 46) Relapsers (N = 42) Age, years, mean(SD) Male, n ( ) Body weight, kg, mean (SD) Baseline HCV RNA, log IU/ml, mean (SD) Baseline HCV RNA . 400,000 IU/mL, n ( ) APRI, mean (SD) AST, IU/l, mean (SD) ALT, IU/l, mean (SD) Rs8099917 TT genotype, n ( ) Previous optimal treatment regimen*, n ( ) 58.6 (9.6) 25 (54.3) 64.2 (8.6) 5.45 (0.81) 23 (50.0) 2.05 (1.55) 108.6 (73.9) 159.9 (130.6) 40 (87.0) 31 (67.4) 58.6 (10.0) 23 (54.8) 63.7 (8.9) 5.39 (0.81) 20 (47.6) 1.99 (1.44) 108.8 (75.9) 164.3 (135.5) 36 (85.7) 28 (66.7)Non-responders (N = 4) P value 58.0 (4.2) 2 (50.0) 1531364 69.1 (1.7) 5.99 (0.60) 3 (75.0) 2.60 (2.69) 106.8 (57.3) 113.8 (41.3) 4 (100) 3 (75.0) 0.90 1 0.15 0.16 0.61 0.46 0.96 0.47 1Note: SD: standard deviation; AST: aspartate aminotransferase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index. *defined as patients who had received 24 weeks of peginterferon/ribavirin doi:10.1371/journal.pone.0058882.tfactor predictive of an SVR was previous relapse (table 3). Among patients who previously relapsed, the SVR rate was substantially higher in patients with an RVR and significantly higher in patients achieving an EVR compared with their counterparts (table 4). Multivariate analysis revealed that the only factor predictive of an SVR for previous relapsers was the achievement of an EVR (table 3).EVR provided a negative predictive value of 100 . The positive predictive value for an SVR was similar between patients with a RVR 18204824 (80 for all patients and 85 for relapsers) and an EVR (77 for all patients and 83 for relapsers). The achievement of an EVR provided a better accuracy in predicting an SVR (88 for all patients and 83 for relapsers) compared to the factor of a RVR (74 for all patients and 75 for relapsers).On-treatment responses in predicting treatment outcomeBecause the achievement of an EVR, but not a RVR, was independently predictive of treatment outcome among relapsers, we further analyzed the accuracy of the two on-treatment factors in predicting an SVR. As shown in table 5, the achievement of Epigenetic Reader Domain anInfluence of IL-28B genetic variants on treatment responsesTreatment responses including rates of RVR (77.5 vs. 66.7 , P = 0.62), EVR (95.0 vs. 83.3 , P = 0.35), EOTVR (92.3 vs. 83.3 , P = 0.44) and SVR (72.5 vs.Responders, relapsers had significantly higher rates of EOTVR (95.2 vs. 50.0 , P = 0.03) and SVR (78.6 vs. 0 , P = 0.004) and a lower relapse rate (17.5 vs. 100 , P = 0.04). As shown in table 2, neither any baseline factor including host IL-28B genotype nor previous virological response was significantly associated with a higher RVR rate. Lower baseline HCV RNA levels, previous virological relapse and the achievement of a RVR and an EVR were factors that were significantly associated with an SVR in the univariate analysis (table 2). Multivariate analysis revealed that the onlyAssessment of efficacyA rapid virological response (RVR) was defined as seronegativity of HCV RNA at week 4 of treatment. An EVR was defined as a seronegative or at least a 2-log10 decrease from baseline in the serum HCV RNA at week 12 of treatment. An end-of-treatment virological response (EOTVR) was defined as seronegativity of HCV RNA at the end of treatment. The endpoint of the study was the achievement of a sustained virological response (SVR), whichHCV-2 RetreatmentTable 1. Basic demographic, virological, and clinical features of HCV genotype 2 patients who failed interferon-based therapy.All patients (N = 46) Relapsers (N = 42) Age, years, mean(SD) Male, n ( ) Body weight, kg, mean (SD) Baseline HCV RNA, log IU/ml, mean (SD) Baseline HCV RNA . 400,000 IU/mL, n ( ) APRI, mean (SD) AST, IU/l, mean (SD) ALT, IU/l, mean (SD) Rs8099917 TT genotype, n ( ) Previous optimal treatment regimen*, n ( ) 58.6 (9.6) 25 (54.3) 64.2 (8.6) 5.45 (0.81) 23 (50.0) 2.05 (1.55) 108.6 (73.9) 159.9 (130.6) 40 (87.0) 31 (67.4) 58.6 (10.0) 23 (54.8) 63.7 (8.9) 5.39 (0.81) 20 (47.6) 1.99 (1.44) 108.8 (75.9) 164.3 (135.5) 36 (85.7) 28 (66.7)Non-responders (N = 4) P value 58.0 (4.2) 2 (50.0) 1531364 69.1 (1.7) 5.99 (0.60) 3 (75.0) 2.60 (2.69) 106.8 (57.3) 113.8 (41.3) 4 (100) 3 (75.0) 0.90 1 0.15 0.16 0.61 0.46 0.96 0.47 1Note: SD: standard deviation; AST: aspartate aminotransferase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index. *defined as patients who had received 24 weeks of peginterferon/ribavirin doi:10.1371/journal.pone.0058882.tfactor predictive of an SVR was previous relapse (table 3). Among patients who previously relapsed, the SVR rate was substantially higher in patients with an RVR and significantly higher in patients achieving an EVR compared with their counterparts (table 4). Multivariate analysis revealed that the only factor predictive of an SVR for previous relapsers was the achievement of an EVR (table 3).EVR provided a negative predictive value of 100 . The positive predictive value for an SVR was similar between patients with a RVR 18204824 (80 for all patients and 85 for relapsers) and an EVR (77 for all patients and 83 for relapsers). The achievement of an EVR provided a better accuracy in predicting an SVR (88 for all patients and 83 for relapsers) compared to the factor of a RVR (74 for all patients and 75 for relapsers).On-treatment responses in predicting treatment outcomeBecause the achievement of an EVR, but not a RVR, was independently predictive of treatment outcome among relapsers, we further analyzed the accuracy of the two on-treatment factors in predicting an SVR. As shown in table 5, the achievement of anInfluence of IL-28B genetic variants on treatment responsesTreatment responses including rates of RVR (77.5 vs. 66.7 , P = 0.62), EVR (95.0 vs. 83.3 , P = 0.35), EOTVR (92.3 vs. 83.3 , P = 0.44) and SVR (72.5 vs.

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