The societal burden of chronic liver diseases: results from the COME study.

OBJECTIVE: Chronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with CLDs at different stages and with different aetiologies. DESIGN: A cost-of-illness study was conducted. Direct costs, productivity loss and HRQoL were estimated in patients with chronic hepatitis, cirrhosis hepatocellular carcinoma (HCC) or where orthotopic liver transplantation (OLT) had been performed, for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, or in those with liver disease from other causes. Patients were retrospectively observed for 6 months. The societal perspective was adopted to calculate costs. RESULTS: In total, 1088 valid patients (median age=59.5 years, 60% men) were enrolled. 61% had chronic hepatitis, 20% cirrhosis, 8% HCC and 12% underwent OLT. HCV infection was identified in 52% and HBV infection in 29% of the patients. Adjusted mean direct costs increased from €3000/patient-month in HBV infected patients with OLT. Antiviral treatment was the cost driver in patients with hepatitis, while hospital costs were the driver in the other subgroups. Absenteeism increased from HBV-infected patients with hepatitis (0.7 day/patient-month) to patients with OLT with other aetiologies (3.7 days/patient-month). HRQoL was on average more compromised in cirrhosis and patients with HCC, than in hepatitis and patients with OLT. HBV-infected patients generated higher direct costs, patients with other aetiologies generated the highest productivity loss and HCV-infected patients reported the worst HRQoL levels. CONCLUSIONS: The present study can be considered a benchmark for future research and to guide policies aimed at maximising the cost-effective of the interventions

Emerging biological agents for hepatitis C

Introduction: New direct-acting antiviral agents have changed the landscape of treatment of chronic HCV infection. Despite current treatments are well tolerated with a high rate of sustained virological response (SVR), some medical needs remain. Nowadays there are a large number of approved medications for the treatment of HCV infection; nevertheless, new studies are conducted to find new agents and new combinations. Areas covered: A literature research of new antiviral compounds indicated for the treatment of HCV infection was achieved by an online search of medication undergoing development on Pubmed and clinicalTrials.gov clinical trials registry. We considered phase I/II studies and some randomized Phase III trials. Expert opinion: More knowledge about impact of HCV eradication on disease progression and more confidence regarding drug-drug interaction are needed. Furthermore, each treatment should be individualized targeting the patients needs with the aim not only to obtain viral suppression but also to stop progression of liver disease and HCV related conditions, and to improve patient health status

Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria

Background and Aim: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. Methods: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. Results: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9–16). The median time on the waitlist was 92 (41–170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6–6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). Conclusions: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data

The societal burden of chronic liver diseases: results from the COME study

OBJECTIVE: Chronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with CLDs at different stages and with different aetiologies. DESIGN: A cost-of-illness study was conducted. Direct costs, productivity loss and HRQoL were estimated in patients with chronic hepatitis, cirrhosis hepatocellular carcinoma (HCC) or where orthotopic liver transplantation (OLT) had been performed, for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, or in those with liver disease from other causes. Patients were retrospectively observed for 6 months. The societal perspective was adopted to calculate costs. RESULTS: In total, 1088 valid patients (median age=59.5 years, 60% men) were enrolled. 61% had chronic hepatitis, 20% cirrhosis, 8% HCC and 12% underwent OLT. HCV infection was identified in 52% and HBV infection in 29% of the patients. Adjusted mean direct costs increased from <€200/patient-month in HCV-infected patients with hepatitis to >€3000/patient-month in HBV infected patients with OLT. Antiviral treatment was the cost driver in patients with hepatitis, while hospital costs were the driver in the other subgroups. Absenteeism increased from HBV-infected patients with hepatitis (0.7 day/patient-month) to patients with OLT with other aetiologies (3.7 days/patient-month). HRQoL was on average more compromised in cirrhosis and patients with HCC, than in hepatitis and patients with OLT. HBV-infected patients generated higher direct costs, patients with other aetiologies generated the highest productivity loss and HCV-infected patients reported the worst HRQoL levels. CONCLUSIONS: The present study can be considered a benchmark for future research and to guide policies aimed at maximising the cost-effective of the interventions

Cost-effectiveness of pretransplant sofosbuvir for preventing recurrent hepatitis C virus infection after liver transplantation

Abstract There are reports of pretransplant sofosbuvir (SOF) plus ribavirin being effective in preventing recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). The aim of this study was to assess the cost-effectiveness of this strategy in the area served by the North Italy Transplant program. We retrospectively assessed the impact of HCV infection on post-LT survival in 2376 consecutive adult patients (MELD ≤ 25, unknown genotype, period 2004-2009) and the prevalence costs of conventional standard of care (SOC) antiviral therapy (pegylated interferon plus ribavirin) after LT. A Markov model was developed to compare two strategies: 12-24 weeks of SOF+ ribavirin for pre-LT anti-HCV treatment versus on-demand post-LT SOC antiviral therapy. Among the 1794 patients undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after LT (mean cost of drugs and adverse effect management = 14,421€ per patient). HCV etiology had a strong impact on post-LT survival (hazard ratio = 1.59, 95% CI = 1.22-2.09, P = 0.0007). After Monte Carlo simulation, pre-LT SOF therapy showed a median survival benefit of 1.5 quality-adjusted life years and an Incremental cost-effectiveness ratio (ICER) of 30,663€/QALY, proving cost-effective in our particular Italian scenario. The costs of SOF therapy, sustained viral response rate 12 weeks after LT, and recipient's age were the main ICER predictors at multivariate analysis. This study proposes a dynamic model based on real-life data from northern Italy for adjusting the costs of pre-LT direct-acting antiviral therapies to the actual sustained virological response reached after LT. © 2015 Steunstichting ESOT. KEYWORDS: cost-effectiveness analysis; hepatitis C virus infection; liver transplantation; recurrent HCV; sofosbuvi