A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12\ua0weeks, and sofosbuvir-ledipasvir alone for 24\ua0weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12\ua0weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24\ua0weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24\ua0weeks, respectively (P\ua0=\ua0.002). The baseline characteristics of patients treated for 12\ua0weeks were significantly different from those treated for 24\ua0weeks as regards their younger age (P\ua0=\ua0.002), prevalence of Child-Pugh class A (P\ua0=\ua0.002), lower MELD scores (P\ua0=\ua0.001) and smaller number of nonresponders (P\ua0=\ua0.04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P\ua0=\ua0.007 and P\ua0=\ua0.008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12\ua0weeks was less effective than sofosbuvir-ledipasvir alone given for 24\ua0weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients

Hepatitis C virus clearance after direct-acting antivirals in cirrhotic patients by stages of liver impairment: the ITAL-C network study

Background and Aims: HCV-infected patients with decompensated cirrhosis, and in particular those Child-Pugh-Turcotte (CPT) class C, are usually excluded from studies investigating the sustained virological response (SVR12) to new direct-acting antivirals (DAAs). A more refined classification of cirrhotic patients has been provided by D’Amico et al. In this system stage 1 includes patients without portal hypertension, stage 2 those with esophageal varices, stage 3 patients who bled from varices, stage 4 patients with a single episode of decompensation events, and stage 5 those with multiple decompensation events. To assess the SVR12 after therapy in patients with advanced fibrosis and cirrhosis stratified according to the D’Amico” system. To evaluate the functional outcome during the follow up after treatment. Methods:We investigated a cohort of 2612 patients, from a network of 24 Italian centers, with chronic HCV infection and advanced fibrosis (no. = 575) or cirrhosis (no. = 2037). Different DAAs schedules were administered at the physicians’ choice, in accordance with national and international guidelines. All patients have completed 3 months of follow-up post treatment. Results: At exception of bilirubin levels, numbers of patients with normal albumin and INR values increased significantly in respect to baseline. Circulating platelets and creatinine levels increased significantly in respect to baseline. A remarkable increase in the numbers of CPT class A patients became apparent, whose frequency increased from 35.9% to 80.3% (p < 0.001). During the 3 month post-treatment follow up, no decompensation events were detected in patients with advanced hepatic fibrosis; a single patient developed HCC, and one patient died for acute leukemia. Of the 1739 stage 1 and 2 cirrhotics, 33 patients (1.9%) manifested events of decompensation or a HCC, and 1 of them died for uncontrolled esophageal bleed. Among the 277 decompensated cirrhotics (stage 3 to 5), 25 subjects (9.0%) experienced single or multiple events or a HCC, 4 were transplanted being HCVRNA negative at the time of the OLT,1 died for acute hepatic failure and 1 for diabetic complications. Results are shown in the Table. Conclusions: Our findings support the safety and the efficacy of DAAs treatment even in patients with portal hypertension and decompensated liver disease (stages 3–5 or CPT class C)

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65\ua0years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100\ua0mg) and twice-daily dasabuvir (250\ua0mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12\ua0weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5\ua0g/dL (OR 2.04: 95% CI 1.0\u20134.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3\u20139.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2\ua0mg/dL (OR 4.9: 95% CI 1.17\u201320.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65&amp;nbsp;years with HCV genotype 1 cirrhosis

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65\ua0years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100\ua0mg) and twice-daily dasabuvir (250\ua0mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12\ua0weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5\ua0g/dL (OR 2.04: 95% CI 1.0\u20134.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3\u20139.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2\ua0mg/dL (OR 4.9: 95% CI 1.17\u201320.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

PurposeTo analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years.MethodsWe collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r+DSV+RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12).ResultsPatients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin &lt;3.5g/dL (OR 2.04: 95% CI 1.0-4.2, p&lt;0.05) and hypertension (OR 4.6: 95% CI 2.3-9.2, p&lt;0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin &lt;2mg/dL (OR 4.9: 95% CI 1.17-20.71, p=0.029) as the only variable independently associated with SVR12.ConclusionOur findings suggest that OBV/PTV/r+DSV+RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. METHODS: In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. FINDINGS: 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83-12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. INTERPRETATION: Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practic

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy