L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Direct Arylations via C–H Bond Functionalization of 1,2,3-Triazoles by a Reusable Pd/C Catalyst Under Solvent-Free Conditions

Fully substituted triazoles are synthesized by a sustainable direct arylation reaction performed under solvent-free conditions and in the presence of a recyclable Pd/C heterogeneous catalyst. Exclusion of air as well as anhydrous conditions are not required, enabling a convenient synthesis of 1,4,5-trisubstituted 1,2,3-triazoles and 1,2,3-triazole-fused isoindolines starting from 1,4-disubstituted 1,2,3-triazoles, easily prepared via click chemistry, and functionalized aryl iodides

EARLY PREDICTION OF LIVER RELATED EVENTS (LRE)IN PATIENT WITH ESTABLISHED HCV RECURRENT DISEASEAFTER LIVER TRANSPLANTATION BY LIVER STIFFNESS MEASUREMENT (LSM)

EARLY PREDICTION OF LIVER RELATED EVENTS (LRE)IN PATIENT WITH ESTABLISHED HCV RECURRENT DISEASEAFTER LIVER TRANSPLANTATION BY LIVER STIFFNESS MEASUREMENT (LSM

Liver stiffness measurments is able to predict graft failure in patients with established HCV recurrence after Liver Transplantation

Liver stiffness measurments is able to predict graft failure in patients with established HCV recurrence after Liver Transplantatio

Solvent-free Reactions for the Synthesis of Indolenine-based Squaraines and Croconaines: Comparison of Thermal Heating, Mechanochemical Milling, and IR Irradiation

Squaraines and croconaines are organic dyes characterized by intense absorption in the visible or near-infrared spectral regions with applications ranging from biology to material sciences. They are commonly synthesized by condensation reactions of oxocarbonic acids (squaric or croconic acid, respectively) with electron-rich aromatic compounds in high-boiling organic solvents. Here, a simple, cost-effective, and environmentally benign process was developed for the synthesis of indolenine-based squaraines and croconaines under solvent-free conditions. Protocols based on conventional thermal heating, mechanochemical milling, and IR-light activation were compared

Antiviral activity and safety profile of silibinin in HCV patients with advanced fibrosis after liver transplantation: a randomized clinical trial

Response to interferon-based therapies in HCV recurrence after liver transplantation (LT) is unsatisfactory, and major safety issues aroused in preliminary experience with boceprevir and telaprevir. As transplant community identified HCV viral clearance as a critical matter, efficacious and safe anti-HCV therapies are awaited. The aim of this study was to assess efficacy and safety of intravenous silibinin monotherapy in patients with established HCV recurrence after LT, nonresponders to pegylated interferon and ribavirin. This is a single center, prospective, randomized, parallel-group, double-blind, placebo-controlled, phase 2 trial including 20 patients randomly assigned (3:1) to receive daily 20 mg/kg of intravenous silibinin or saline as placebo, for 14 consecutive days. On day 14 of treatment, viral load decreased by 2.30 ± 1.32 in silibinin group versus no change in the placebo group (P = 0.0002). Sixteen days after the end of the treatment, viral load mean values were similar to baseline. Treatment resulted well tolerated apart from a transient and reversible increase in bilirubin. Neither changes in immunosuppressant through levels nor dosage adjustments were necessary. Silibinin monotherapy has a significant antiviral activity in patients with established HCV recurrence on the graft not responding to standard therapy and confirms safety and tolerability without interaction with immunosuppressive drug

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)

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11\ub13.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival

Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P<0.04), early virological response (P<0.0001), and adherence to therapy (P<0.0001) were independent predictors for SVR. In conclusion, female gender represents an independent negative prognostic factor for the outcome of HCV antiviral therapy after LT