Guest guest Posted April 27, 2011 Report Share Posted April 27, 2011 J Med Virol. 2011 Jun;83(6):1016-22. doi: 10.1002/jmv.22094. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@.... Abstract Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016-1022, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503914 [PubMed - in process] ----------------------------------------------------------------- Eur J Gastroenterol Hepatol. 2011 May;23(5):375-81. Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe. Husa P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Urbanek P. Source aDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine, Masaryk University Brno, Brno bHepatologicka Poradna, Praha cDepartment of Internal Diseases, Ustredni Vojenska Nemocnice Praha-Stresovice, Czech Republic dSt Cyril and Method's Hospital, Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje, Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel, Switzerland. Abstract OBJECTIVE: To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients. METHODS: HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 μg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12. RESULTS: A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%). CONCLUSION: The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin. PMID: 21502923 [PubMed - in process] _________________________________________________________ J Med Virol. 2011 Jun;83(6):1005-15. doi: 10.1002/jmv.22072. Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis. Pascarella S, Clément S, Guilloux K, Conzelmann S, Penin F, Negro F. Source Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Abstract Glucose metabolism disturbances, including insulin resistance and type 2 diabetes, are frequent and important cofactors of hepatitis C. Increasing epidemiological and experimental data suggest that all major genotypes of hepatitis C virus (HCV), albeit to a different extent, cause insulin resistance. The HCV core protein has been shown to be sufficient to impair insulin signaling in vitro through several post-receptorial mechanisms, mostly via the activation of suppressor of cytokine signaling (SOCS) family members and the consequent decrease of insulin receptor substrate-1 (IRS-1). The levels of IRS-1 and SOCS were investigated upon expression of the core protein of HCV genotypes 1-4. Furthermore, the core protein sequences were analyzed to identify the amino acid residues responsible for IRS-1 decrease, with particular regard to SOCS mRNA deregulation. The results suggest that the activation of SOCS family members is a general mechanism associated with the common HCV genotypes. A rare genotype 1b variant, however, failed to activate any of the SOCS tested: this allowed to analyze in detail the distinct amino acid sequences responsible for SOCS deregulation. By combining approaches using intergenotypic chimeras and site-directed mutagenesis, genetic evidence was provided in favor of a role of amino acids 49 and 131 of the HCV core-encoding sequence in mediating SOCS transactivation. J. Med. Virol. 83:1005-1015, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503913 [PubMed - in process] Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 27, 2011 Report Share Posted April 27, 2011 J Med Virol. 2011 Jun;83(6):1016-22. doi: 10.1002/jmv.22094. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@.... Abstract Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016-1022, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503914 [PubMed - in process] ----------------------------------------------------------------- Eur J Gastroenterol Hepatol. 2011 May;23(5):375-81. Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe. Husa P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Urbanek P. Source aDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine, Masaryk University Brno, Brno bHepatologicka Poradna, Praha cDepartment of Internal Diseases, Ustredni Vojenska Nemocnice Praha-Stresovice, Czech Republic dSt Cyril and Method's Hospital, Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje, Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel, Switzerland. Abstract OBJECTIVE: To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients. METHODS: HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 μg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12. RESULTS: A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%). CONCLUSION: The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin. PMID: 21502923 [PubMed - in process] _________________________________________________________ J Med Virol. 2011 Jun;83(6):1005-15. doi: 10.1002/jmv.22072. Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis. Pascarella S, Clément S, Guilloux K, Conzelmann S, Penin F, Negro F. Source Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Abstract Glucose metabolism disturbances, including insulin resistance and type 2 diabetes, are frequent and important cofactors of hepatitis C. Increasing epidemiological and experimental data suggest that all major genotypes of hepatitis C virus (HCV), albeit to a different extent, cause insulin resistance. The HCV core protein has been shown to be sufficient to impair insulin signaling in vitro through several post-receptorial mechanisms, mostly via the activation of suppressor of cytokine signaling (SOCS) family members and the consequent decrease of insulin receptor substrate-1 (IRS-1). The levels of IRS-1 and SOCS were investigated upon expression of the core protein of HCV genotypes 1-4. Furthermore, the core protein sequences were analyzed to identify the amino acid residues responsible for IRS-1 decrease, with particular regard to SOCS mRNA deregulation. The results suggest that the activation of SOCS family members is a general mechanism associated with the common HCV genotypes. A rare genotype 1b variant, however, failed to activate any of the SOCS tested: this allowed to analyze in detail the distinct amino acid sequences responsible for SOCS deregulation. By combining approaches using intergenotypic chimeras and site-directed mutagenesis, genetic evidence was provided in favor of a role of amino acids 49 and 131 of the HCV core-encoding sequence in mediating SOCS transactivation. J. Med. Virol. 83:1005-1015, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503913 [PubMed - in process] Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 27, 2011 Report Share Posted April 27, 2011 J Med Virol. 2011 Jun;83(6):1016-22. doi: 10.1002/jmv.22094. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@.... Abstract Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016-1022, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503914 [PubMed - in process] ----------------------------------------------------------------- Eur J Gastroenterol Hepatol. 2011 May;23(5):375-81. Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe. Husa P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Urbanek P. Source aDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine, Masaryk University Brno, Brno bHepatologicka Poradna, Praha cDepartment of Internal Diseases, Ustredni Vojenska Nemocnice Praha-Stresovice, Czech Republic dSt Cyril and Method's Hospital, Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje, Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel, Switzerland. Abstract OBJECTIVE: To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients. METHODS: HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 μg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12. RESULTS: A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%). CONCLUSION: The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin. PMID: 21502923 [PubMed - in process] _________________________________________________________ J Med Virol. 2011 Jun;83(6):1005-15. doi: 10.1002/jmv.22072. Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis. Pascarella S, Clément S, Guilloux K, Conzelmann S, Penin F, Negro F. Source Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Abstract Glucose metabolism disturbances, including insulin resistance and type 2 diabetes, are frequent and important cofactors of hepatitis C. Increasing epidemiological and experimental data suggest that all major genotypes of hepatitis C virus (HCV), albeit to a different extent, cause insulin resistance. The HCV core protein has been shown to be sufficient to impair insulin signaling in vitro through several post-receptorial mechanisms, mostly via the activation of suppressor of cytokine signaling (SOCS) family members and the consequent decrease of insulin receptor substrate-1 (IRS-1). The levels of IRS-1 and SOCS were investigated upon expression of the core protein of HCV genotypes 1-4. Furthermore, the core protein sequences were analyzed to identify the amino acid residues responsible for IRS-1 decrease, with particular regard to SOCS mRNA deregulation. The results suggest that the activation of SOCS family members is a general mechanism associated with the common HCV genotypes. A rare genotype 1b variant, however, failed to activate any of the SOCS tested: this allowed to analyze in detail the distinct amino acid sequences responsible for SOCS deregulation. By combining approaches using intergenotypic chimeras and site-directed mutagenesis, genetic evidence was provided in favor of a role of amino acids 49 and 131 of the HCV core-encoding sequence in mediating SOCS transactivation. J. Med. Virol. 83:1005-1015, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503913 [PubMed - in process] Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 27, 2011 Report Share Posted April 27, 2011 J Med Virol. 2011 Jun;83(6):1016-22. doi: 10.1002/jmv.22094. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@.... Abstract Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016-1022, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503914 [PubMed - in process] ----------------------------------------------------------------- Eur J Gastroenterol Hepatol. 2011 May;23(5):375-81. Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe. Husa P, Oltman M, Ivanovski L, Rehák V, Messinger D, Tietz A, Urbanek P. Source aDepartment of Infectious Diseases, Faculty Hospital and Faculty of Medicine, Masaryk University Brno, Brno bHepatologicka Poradna, Praha cDepartment of Internal Diseases, Ustredni Vojenska Nemocnice Praha-Stresovice, Czech Republic dSt Cyril and Method's Hospital, Bratislava, Slovakia eClinic for Infectious Diseases, Clinical Center Skopje, Skopje, FYR Macedonia fBiometrics, IST GmbH, Mannheim, Germany gRoche, Basel, Switzerland. Abstract OBJECTIVE: To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients. METHODS: HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 μg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12. RESULTS: A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%). CONCLUSION: The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin. PMID: 21502923 [PubMed - in process] _________________________________________________________ J Med Virol. 2011 Jun;83(6):1005-15. doi: 10.1002/jmv.22072. Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis. Pascarella S, Clément S, Guilloux K, Conzelmann S, Penin F, Negro F. Source Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Abstract Glucose metabolism disturbances, including insulin resistance and type 2 diabetes, are frequent and important cofactors of hepatitis C. Increasing epidemiological and experimental data suggest that all major genotypes of hepatitis C virus (HCV), albeit to a different extent, cause insulin resistance. The HCV core protein has been shown to be sufficient to impair insulin signaling in vitro through several post-receptorial mechanisms, mostly via the activation of suppressor of cytokine signaling (SOCS) family members and the consequent decrease of insulin receptor substrate-1 (IRS-1). The levels of IRS-1 and SOCS were investigated upon expression of the core protein of HCV genotypes 1-4. Furthermore, the core protein sequences were analyzed to identify the amino acid residues responsible for IRS-1 decrease, with particular regard to SOCS mRNA deregulation. The results suggest that the activation of SOCS family members is a general mechanism associated with the common HCV genotypes. A rare genotype 1b variant, however, failed to activate any of the SOCS tested: this allowed to analyze in detail the distinct amino acid sequences responsible for SOCS deregulation. By combining approaches using intergenotypic chimeras and site-directed mutagenesis, genetic evidence was provided in favor of a role of amino acids 49 and 131 of the HCV core-encoding sequence in mediating SOCS transactivation. J. Med. Virol. 83:1005-1015, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21503913 [PubMed - in process] Quote Link to comment Share on other sites More sharing options...
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