AIM: To determine the safety profile of new hepatitis C virus(HCV) treatments in liver transplant(LT) recipients with recurrent HCV infection.METHODS: Forty-two patients were identified with recurrent HCV infection th...AIM: To determine the safety profile of new hepatitis C virus(HCV) treatments in liver transplant(LT) recipients with recurrent HCV infection.METHODS: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events(SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIVinfected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. RESULTS: Median age of the 42 patients was 60 years [Interquartile Range(IQR): 56-65 years], 33%(14/42) were female, 21%(9/42) were Hispanic, and 9%(4/42) were Black. The median time from transplant to treatment initiation was 5.4 years(IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62%(8/13) patients, while 54%(7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31%(95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin(OR = 0.61 per g/d L, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate(OR = 0.95 per m L/min per 1.73 m^2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin(OR = 2.43 per mg/d L, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.CONCLUSION: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.展开更多
AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received ...AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.展开更多
AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV...AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.展开更多
AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 20...AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency viruspositive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response(SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response(FVR) was defined as undetectable HCV RNA at week-4(telaprevir) or week-8(boceprevir). RESULTS The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis(FIB-4 ≥ 3.25). Only 42%(94/223) of patients achieved SVR24 on an intention-totreat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio(OR) = 5.92, 95% confidence interval(CI): 2.34-14.96], HCV sub-genotype 1b(OR = 2.81, 95%CI: 1.45-5.44), platelet count(OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28 B CC genotype(OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25%(27/104) of patients with an end-oftreatment response and was associated with non-FVR(OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a(OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25(OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION The SVR rate was 42% with telaprevir-or boceprevirbased triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.展开更多
基金Supported by National Institutes of Health,No.DA031095 and No.DK090317
文摘AIM: To determine the safety profile of new hepatitis C virus(HCV) treatments in liver transplant(LT) recipients with recurrent HCV infection.METHODS: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events(SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIVinfected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. RESULTS: Median age of the 42 patients was 60 years [Interquartile Range(IQR): 56-65 years], 33%(14/42) were female, 21%(9/42) were Hispanic, and 9%(4/42) were Black. The median time from transplant to treatment initiation was 5.4 years(IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62%(8/13) patients, while 54%(7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31%(95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin(OR = 0.61 per g/d L, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate(OR = 0.95 per m L/min per 1.73 m^2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin(OR = 2.43 per mg/d L, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.CONCLUSION: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.
基金Supported by The Grants No.R01 DK090317 and No.R01 DA031095(in part)
文摘AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.
基金Supported by Janssen Scientific Affairs and National Institutes of Health,Nos.DA031095 and DK090317
文摘AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.
基金Supported by Janssen Scientific Affairs,LLC(partially)to Andrea D Branch to conduct the studyNational Institute of Health(NIH),Nos.DK090317 and DA031095(partially)to Andrea D Branch to conduct the study
文摘AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency viruspositive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response(SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response(FVR) was defined as undetectable HCV RNA at week-4(telaprevir) or week-8(boceprevir). RESULTS The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis(FIB-4 ≥ 3.25). Only 42%(94/223) of patients achieved SVR24 on an intention-totreat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio(OR) = 5.92, 95% confidence interval(CI): 2.34-14.96], HCV sub-genotype 1b(OR = 2.81, 95%CI: 1.45-5.44), platelet count(OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28 B CC genotype(OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25%(27/104) of patients with an end-oftreatment response and was associated with non-FVR(OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a(OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25(OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION The SVR rate was 42% with telaprevir-or boceprevirbased triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.
