The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform

Yoshiyuki Suzuki - One of the best experts on this subject based on the ideXlab platform.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for hcv genotype 1 failures to prior ns5a inhibitors regimens
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that Ledipasvir/Sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (

  • retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to hcv genotype 1 in japan
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of Ledipasvir Plus Sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.

  • Retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to HCV genotype 1 in Japan
    Journal of medical virology, 2016
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (

Norio Akuta - One of the best experts on this subject based on the ideXlab platform.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for hcv genotype 1 failures to prior ns5a inhibitors regimens
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that Ledipasvir/Sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (

  • retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to hcv genotype 1 in japan
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of Ledipasvir Plus Sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.

  • Retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to HCV genotype 1 in Japan
    Journal of medical virology, 2016
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (

Tetsuya Hosaka - One of the best experts on this subject based on the ideXlab platform.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for hcv genotype 1 failures to prior ns5a inhibitors regimens
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that Ledipasvir/Sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (

  • retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to hcv genotype 1 in japan
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of Ledipasvir Plus Sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.

  • Retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to HCV genotype 1 in Japan
    Journal of medical virology, 2016
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (

Fumitaka Suzuki - One of the best experts on this subject based on the ideXlab platform.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for hcv genotype 1 failures to prior ns5a inhibitors regimens
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that Ledipasvir/Sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (

  • retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to hcv genotype 1 in japan
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of Ledipasvir Plus Sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.

  • Retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to HCV genotype 1 in Japan
    Journal of medical virology, 2016
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (

Yusuke Kawamura - One of the best experts on this subject based on the ideXlab platform.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for hcv genotype 1 failures to prior ns5a inhibitors regimens
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (<3.25) as significant determinants of SVR12. The SVR12 rates were significantly lower in patients with FIB4 index of ≥3.25 and had not responded to prior treatment, relative to others. The specificity, and positive- and negative-predictive values were high for prediction of poor response based on the combination of two predictors. In conclusion, our study indicated that Ledipasvir/Sofosbuvir is a potentially useful salvage treatment for patients who fail prior NS5A inhibitors-based therapy. Response to prior treatment was an important predictor of retreatment efficacy.

  • Ledipasvir Plus Sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens.
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    : There is little information on retreatment efficacy and predictors of the combination of Ledipasvir and Sofosbuvir (Ledipasvir/Sofosbuvir) for patients who fail to respond to NS5A inhibitors. NS5A resistance variants are known to persist for long periods after such treatment. Here, we evaluated 54 patients with chronic HCV genotype 1b infection, free of decompensated cirrhosis, and hepatocellular carcinoma, for sustained virological response after 12 weeks (SVR12) of once-daily treatment with 90 mg Ledipasvir and 400 mg Sofosbuvir. Intention-to-treat analysis showed SVR12 of 70%. Using ultra-deep sequencing, non-responder to Ledipasvir/Sofosbuvir showed no change in the rates of detection of NS5A and NS5B resistant-variants at re-elevation of viral loads, relative to baseline. According to response to prior treatment, SVR12 rates were 18, 69, 94, and 100% in non response, viral breakthrough, relapse, and discontinuation due to adverse events, respectively. SVR12 rates in non response were significantly lower than those of the others. Multivariate analysis identified response to previous treatment (failure except for non response) and FIB4 index (

  • retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to hcv genotype 1 in japan
    Journal of Medical Virology, 2017
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of Ledipasvir Plus Sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.

  • Retreatment efficacy and predictors of Ledipasvir Plus Sofosbuvir to HCV genotype 1 in Japan
    Journal of medical virology, 2016
    Co-Authors: Norio Akuta, Shunichiro Fujiyama, Tetsuya Hosaka, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Satoshi Saitoh, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki
    Abstract:

    Predictors of treatment efficacy with Ledipasvir Plus Sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of Ledipasvir Plus Sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by Ledipasvir 90 mg Plus Sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir Plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that Ledipasvir Plus Sofosbuvir was effective to one case of failures to daclatasvir Plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (