Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. CONCLUSIONS: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease

Antiviral Therapy for HCV-Associated Cryoglobulinemic Glomerulonephritis: Case Report and Review of the Literature

We describe the case of a 51-year-old woman with HCV-associated cryoglobulinemic glomerulonephritis (GN). She presented mild deterioration of kidney function, non-nephrotic proteinuria, and active urinary sediment. Kidney biopsy showed features of membranoproliferative changes with some sclerosis. Sustained viral response (SVR) was obtained by 6 months of antiviral therapy (peg-IFN-α2a plus ribavirin). SVR was linked with improvement of kidney function and remission of proteinuria. Clinical and virological remission persists over a 25-month follow-up. This case report emphasizes efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis – preliminary but encouraging results exist. We identified by systematic review of the literature 9 studies (156 unique patients); the pooled estimate of frequency of sustained virological response after IFN-based therapy was 0.49 (95% confidence interval, CI: 0.21, 0.77; p < 0.0005; random effects model). Heterogeneity was found (I2 = 98.9%, p < 0.0001). Two possible regimens should be considered for the treatment of HCV-associated cryoglobulinemic GN according to the clinical presentation. Immunosuppressive therapy is recommended for HCV-related kidney disease having aggressive course, and recent evidence supports rituximab (RTX) use with a reduced exposure to corticosteroids. We identified six studies (66 unique patients) on RTX therapy for HCV-associated kidney disease; at the end of RTX therapy, the pooled estimate of the mean decrease in proteinuria was 1.4 g/24 h (95% CI: 0.75, 2.05, p < 0.001); The p test for heterogeneity gave a value of 0.94 (I2 = 0). Several questions related to RTX use remain. HCV-induced GN is uncommon among CKD patients of developed countries, and this clearly hampers prospective controlled clinical trials aimed to evaluate efficacy and safety of antiviral or immunosuppressive therapy in this population

Modeling cost-effectiveness and health gains of a âuniversalâ versus âprioritizedâ hepatitis C virus treatment policy in a real-life cohort

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virusâinfected patients: policy 1, âuniversal,â treat all patients, regardless of fibrosis stage; policy 2, treat only âprioritizedâ patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virusâinfected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policiesâ cost-effectiveness. The patientsâ age and fibrosis stage, assumed DAA treatment cost of â¬15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of â¬30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was â¬8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was â¬19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 postâsustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (â¬15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Conclusion: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814â1825)

Modeling cost-effectiveness and health gains of a \ue2\u80\u9cuniversal\ue2\u80\u9d versus \ue2\u80\u9cprioritized\ue2\u80\u9d hepatitis C virus treatment policy in a real-life cohort

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus\ue2\u80\u93infected patients: policy 1, \ue2\u80\u9cuniversal,\ue2\u80\u9d treat all patients, regardless of fibrosis stage; policy 2, treat only \ue2\u80\u9cprioritized\ue2\u80\u9d patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus\ue2\u80\u93infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies\ue2\u80\u99 cost-effectiveness. The patients\ue2\u80\u99 age and fibrosis stage, assumed DAA treatment cost of \ue2\u82\uac15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of \ue2\u82\uac30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was \ue2\u82\uac8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was \ue2\u82\uac19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post\ue2\u80\u93sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (\ue2\u82\uac15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Conclusion: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814\ue2\u80\u931825)