AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Prog...AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures.Participating physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and analysed.Multivariate analysis was performed to determine predictors of response.RESULTS:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,Caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,Caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HCVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HCVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%respectively.Asian patients were similar to Caucasian patients with regards to on-treatment responses.Patients with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment responses.Those with the IL28 B CC genotype(80%) had higher SVRs than those with the CT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR.Serious adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping rules.CONCLUSION:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.展开更多
Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosi...Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred.Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response(SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4(RVR).In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic directacting antivirals have completed phase Ⅱ/Ⅲ studies(sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR(representing>70% of patients) are suitable for 24-wk treatment with expected SVR rates>80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy,and a detectable HCV RNA at week 12(with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia,wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.展开更多
AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hep...AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula.The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS:Sustained virological response was obtained in 83(47.2%)of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4,12 and 24.The likelihood of sustained virological response could be predicted effectively bythe formulae at weeks 4,12 and 24(the area under the curve of the receiver operating characteristic:0.821, 0.802,and 0.891,respectively),but not at baseline (0.570).The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic.Prediction by this formula was always superior to that by viral kinetics. CONCLUSION:These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.展开更多
文摘AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures.Participating physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and analysed.Multivariate analysis was performed to determine predictors of response.RESULTS:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,Caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,Caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HCVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HCVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%respectively.Asian patients were similar to Caucasian patients with regards to on-treatment responses.Patients with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment responses.Those with the IL28 B CC genotype(80%) had higher SVRs than those with the CT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR.Serious adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping rules.CONCLUSION:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.
文摘Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred.Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response(SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4(RVR).In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic directacting antivirals have completed phase Ⅱ/Ⅲ studies(sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR(representing>70% of patients) are suitable for 24-wk treatment with expected SVR rates>80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy,and a detectable HCV RNA at week 12(with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia,wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.
文摘AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula.The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS:Sustained virological response was obtained in 83(47.2%)of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4,12 and 24.The likelihood of sustained virological response could be predicted effectively bythe formulae at weeks 4,12 and 24(the area under the curve of the receiver operating characteristic:0.821, 0.802,and 0.891,respectively),but not at baseline (0.570).The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic.Prediction by this formula was always superior to that by viral kinetics. CONCLUSION:These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.
