AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection wh...AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women(age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). Relationships between virological response and clinical data were examined by logistic regression analyses. RESULTS The proportions of patients with liver cirrhosis and history of hepatocellular carcinoma(HCC) were 29.0% and 17.3%, respectively. The proportion of patients with prior interferon(IFN)-based therapy was 25.6%. SOF/RBV therapy rapidly decreased HCV RNA levels. Several patients required RBV dose reduction because of anemia or fatigue. Four patients discontinued the therapy. The rates of sustained virological response at 12 wk after the end of treatment were 87.9%(intention to treat: 160/182) and 94.1%(per protocol: 159/169). Multivariate analyses showed that history of HCC or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy. CONCLUSION SOF/RBV therapy for GT2-HCV is safe, highly tolerated, and effective. History of HCC or IFN-based therapy independently reduces the efficacy of this treatment.展开更多
To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to ...To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.METHODSSequences within HCV NS5A[PKR binding domain(PKRBD)and the interferon-sensitivity-determining region(ISDR)]were analysed via direct sequencing in a selected cohort of 72 patients,with a total of 201 treatments[interferon-alpha(IFN-α),n=49;IFN-α+ribavirin(RBV),n=75;pegylated(peg)IFN-α+RBV,n=47;first-generation direct-acting antivirals(DAAs),n=13;and second-generation DAAs,n=17].Of these,48/201 achieved a sustained virological response(SVR)and 153/201 achieved no virological response(NVR).RESULTSFor both regions,treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR(SVR vs NVR;PKRBD:5.82±3 vs 4.86±2 mutations,P=0.045;ISDR:2.65±2 vs 1.51±1.7 mutations,P=0.005).A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR,as shown by sequencing,was associated with patients who usually failed to respond to treatment(PKRBD,P=0.02;ISDR,P=0.001).Moreover,patients showing a post-treatment baseline viral load>600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR(P=0.001).CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments,the likelihood of achieving SVR increases with the genetic variability in the ISDR region(≥2 mutations or number of substitutions from the HCV-J and HCV-1 prototype),especially when the viral load is greater than 600000 IU/mL.展开更多
We devised an extended 72-wk peginterferon--2a/ribavirin therapy regimen for the retreatment of highly intractable cases,i.e.,48-wk peginterferon--2b/ribavirin therapy-intractable cases.Although 2 cases achieved a rap...We devised an extended 72-wk peginterferon--2a/ribavirin therapy regimen for the retreatment of highly intractable cases,i.e.,48-wk peginterferon--2b/ribavirin therapy-intractable cases.Although 2 cases achieved a rapid virological response to 72-wk peginterferon--2a/ribavirin therapy,1 case failed to achieve a sustained virological response.Although the reason for this difference in the effectiveness of 72-wk peginterferon--2a/ribavirin therapy between the cases was unclear,the rebound phenomenon of serum transaminase after48-wk peginterferon--2b/ribavirin therapy and the resultant lower viral load compared to that before 48-wk peginterferon--2b/ribavirin therapy might have influenced the treatment outcome.Thus,it may be beneficial to consider the rebound phenomenon of serum transaminase and the changes in viral load resulting from previous interferon-based therapy and then cau-tiously determine the indication and the timing of the administration of 72-wk peginterferon--2a/ribavirin in highly intractable cases.Further studies should be performed to confirm this strategy.展开更多
文摘AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women(age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). Relationships between virological response and clinical data were examined by logistic regression analyses. RESULTS The proportions of patients with liver cirrhosis and history of hepatocellular carcinoma(HCC) were 29.0% and 17.3%, respectively. The proportion of patients with prior interferon(IFN)-based therapy was 25.6%. SOF/RBV therapy rapidly decreased HCV RNA levels. Several patients required RBV dose reduction because of anemia or fatigue. Four patients discontinued the therapy. The rates of sustained virological response at 12 wk after the end of treatment were 87.9%(intention to treat: 160/182) and 94.1%(per protocol: 159/169). Multivariate analyses showed that history of HCC or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy. CONCLUSION SOF/RBV therapy for GT2-HCV is safe, highly tolerated, and effective. History of HCC or IFN-based therapy independently reduces the efficacy of this treatment.
基金Supported by“Consejería de Salud de la Junta de Andalucía”,No.PI0137/07“Instituto de Salud CarlosⅢ”,No.FISIntrasalud PI010/717
文摘To determine the number of mutations in the NS5A region of the hepatitis C virus(HCV)and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments.METHODSSequences within HCV NS5A[PKR binding domain(PKRBD)and the interferon-sensitivity-determining region(ISDR)]were analysed via direct sequencing in a selected cohort of 72 patients,with a total of 201 treatments[interferon-alpha(IFN-α),n=49;IFN-α+ribavirin(RBV),n=75;pegylated(peg)IFN-α+RBV,n=47;first-generation direct-acting antivirals(DAAs),n=13;and second-generation DAAs,n=17].Of these,48/201 achieved a sustained virological response(SVR)and 153/201 achieved no virological response(NVR).RESULTSFor both regions,treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR(SVR vs NVR;PKRBD:5.82±3 vs 4.86±2 mutations,P=0.045;ISDR:2.65±2 vs 1.51±1.7 mutations,P=0.005).A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR,as shown by sequencing,was associated with patients who usually failed to respond to treatment(PKRBD,P=0.02;ISDR,P=0.001).Moreover,patients showing a post-treatment baseline viral load>600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR(P=0.001).CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments,the likelihood of achieving SVR increases with the genetic variability in the ISDR region(≥2 mutations or number of substitutions from the HCV-J and HCV-1 prototype),especially when the viral load is greater than 600000 IU/mL.
基金Supported by Grants from Merck Sharp&Dohme,Tokyo,JapanChugai Pharmaceutical Co.,Ltd.,Tokyo,Japan to Mori M
文摘We devised an extended 72-wk peginterferon--2a/ribavirin therapy regimen for the retreatment of highly intractable cases,i.e.,48-wk peginterferon--2b/ribavirin therapy-intractable cases.Although 2 cases achieved a rapid virological response to 72-wk peginterferon--2a/ribavirin therapy,1 case failed to achieve a sustained virological response.Although the reason for this difference in the effectiveness of 72-wk peginterferon--2a/ribavirin therapy between the cases was unclear,the rebound phenomenon of serum transaminase after48-wk peginterferon--2b/ribavirin therapy and the resultant lower viral load compared to that before 48-wk peginterferon--2b/ribavirin therapy might have influenced the treatment outcome.Thus,it may be beneficial to consider the rebound phenomenon of serum transaminase and the changes in viral load resulting from previous interferon-based therapy and then cau-tiously determine the indication and the timing of the administration of 72-wk peginterferon--2a/ribavirin in highly intractable cases.Further studies should be performed to confirm this strategy.
