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Papers by Shinn-cherng Chen
Hepatology, 2011
Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the inter... more Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)
Antiviral Research, 2012
a b s t r a c t 35 Background: Both interleukin-28B genetic variants and on-treatment virological... more a b s t r a c t 35 Background: Both interleukin-28B genetic variants and on-treatment virological responses are factors 36 predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare 37 the clinical significance of the two factors. 38 Methods: Rs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 39 48-week peginterferon/ribavirin. 40 Results: Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly 41 higher rapid virological response (RVR, 46.2% vs. 19.2%, P = 0.01) and sustained virological response (SVR, 42 85.3% vs. 42.3%, P < 0.001) rates. Logistic regression analysis revealed that the strongest factor predictive 43 of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 44 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 45 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). How-46 ever, while on-treatment factors were taken into account, the cEVR was the most important determinant 47 to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant 48 in non-RVR patients. 49 Conclusions: Rs8099917 TT genotype is significantly independently predictive of on-treatment virological 50 responses, which were the major determinants of an SVR, in Asian HCV-1 patients. 51 Ó 2011 Published by Elsevier B.V. 52 53 54 55
Journal of Gastroenterology and Hepatology, 2015
Hepatology, 2011
Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the inter... more Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)
Antiviral Research, 2012
a b s t r a c t 35 Background: Both interleukin-28B genetic variants and on-treatment virological... more a b s t r a c t 35 Background: Both interleukin-28B genetic variants and on-treatment virological responses are factors 36 predictive of treatment outcome in hepatitis C virus genotype 1 (HCV-1) patients. We aimed to compare 37 the clinical significance of the two factors. 38 Methods: Rs8099917 genotype and on-treatment responses were determined in 182 HCV-1 patients with 39 48-week peginterferon/ribavirin. 40 Results: Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly 41 higher rapid virological response (RVR, 46.2% vs. 19.2%, P = 0.01) and sustained virological response (SVR, 42 85.3% vs. 42.3%, P < 0.001) rates. Logistic regression analysis revealed that the strongest factor predictive 43 of a RVR was the carriage of rs8099917 TT genotype (odds ratio/95% confidence intervals [OR/CI]: 44 4.25/1.39-13.01). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 45 57.22/6.23-525.37), followed by the carriage of rs8099917 TT genotype (OR/CI: 10.06/3.12-32.44). How-46 ever, while on-treatment factors were taken into account, the cEVR was the most important determinant 47 to an SVR (OR/CI:54.98/9.07-333.38), whereas the influence of rs8099917 genotype became non-significant 48 in non-RVR patients. 49 Conclusions: Rs8099917 TT genotype is significantly independently predictive of on-treatment virological 50 responses, which were the major determinants of an SVR, in Asian HCV-1 patients. 51 Ó 2011 Published by Elsevier B.V. 52 53 54 55
Journal of Gastroenterology and Hepatology, 2015