Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort

Background: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results: We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08–2.85) and increased INR (HR = 2.41; 95% CI 1.51–3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83). Conclusions: Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease

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

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. 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

Economic consequences of anti-HCV treatment of patients diagnosed through screening in Italy : a prospective modelling analysis

To evaluate the cost-consequences of the investment for anti-hepatitis C virus (HCV) treatment by the Italian National Health System (NHS) for patients who will be newly diagnosed through active HCV screening, implemented in Italy from 2020. A previously published Markov model was used to estimate the disease complications avoided and the associated savings over 20 years to treat a standardised population of 10,000 HCV-infected patients diagnosed as a result of screening. Disease progression probabilities and fibrosis stage distribution were based on previously reported data in the literature. Real-life treatment effectiveness and medical expenses for disease management were estimated starting from a representative cohort of HCV-treated patients in Italy (Italian Platform for the Study of Viral Hepatitis Therapies). The breakeven point in time (BPT) was defined as the years required for the initial investment in treatment to be recovered in terms of cumulative costs saved. Over a 20-year time horizon, the treatment of 10,000 standardized patients diagnosed through active HCV screening results in 7769 avoided events of progression, which are associated with €838.73 million net savings accrued by the Italian NHS. The initial investment in treatment is recouped in 4.3 years in the form of savings from disease complications avoided. Investment in treatment of newly diagnosed patients will bring a significant reduction in disease complications, which is associated with great economic benefits. This type of action can reduce the infection rate as well as the clinical and economic disease burden of HCV in Italy. [Abstract copyright: © 2021. The Author(s).

Economic Consequences of Anti-HCV Treatment of Patients Diagnosed Through Screening in Italy: A Prospective Modelling Analysis

Aim To evaluate the cost-consequences of the investment for anti-hepatitis C virus (HCV) treatment by the Italian National Health System (NHS) for patients who will be newly diagnosed through active HCV screening, implemented in Italy from 2020. Methods A previously published Markov model was used to estimate the disease complications avoided and the associated savings over 20 years to treat a standardised population of 10,000 HCV-infected patients diagnosed as a result of screening. Disease progression probabilities and fibrosis stage distribution were based on previously reported data in the literature. Real-life treatment effectiveness and medical expenses for disease management were estimated starting from a representative cohort of HCV-treated patients in Italy (Italian Platform for the Study of Viral Hepatitis Therapies). The breakeven point in time (BPT) was defined as the years required for the initial investment in treatment to be recovered in terms of cumulative costs saved. Results Over a 20-year time horizon, the treatment of 10,000 standardized patients diagnosed through active HCV screening results in 7769 avoided events of progression, which are associated with euro838.73 million net savings accrued by the Italian NHS. The initial investment in treatment is recouped in 4.3 years in the form of savings from disease complications avoided. Conclusion Investment in treatment of newly diagnosed patients will bring a significant reduction in disease complications, which is associated with great economic benefits. This type of action can reduce the infection rate as well as the clinical and economic disease burden of HCV in Italy

Outcomes of advanced liver disease in patients with chronic hepatitis C with and without HIV coinfection following sustained virological response: a real life evaluation in the PITER cohort

Background. Few data are available on liver disease progression following viral eradication due to DAA treatment in HIV/HCV-coinfected patients in real life settings. Methods. Patients consecutively enrolled in the PITER cohort from 2014-2019, with at least 12 weeks follow-up after the end of DAA treatment (median follow-up 38.9 months, range 4.1-60.8), were analysed. Emergence of a liver complication (de novo HCC occurrence or hepatic decompensation) was evaluated in patients with pretreatment diagnosis of liver cirrhosis. Variables independently associated to development of a liver complication after achieving SVR12 were evaluated by Cox regression analysis. Results. We included 244 HIV/HCV-coinfected patients (74.6% men, median age 52, range: 32-77) and 2870 HCV-infected patients (54.1% men, median age 61, range: 20-86). Higher prevalence of HCV genotype 1b was observed in monoinfected patients, whereas genotype 1a and 3 were dominant in coinfected patients. No significant differences in main baseline characteristics and a similar fibrosis stage distribution were observed in both groups. Despite the significant younger age (p<0.001), cirrhotic coinfected patients had higher liver disease severity in terms of Child-Pugh class distribution (p<0.001). Comparable rates of SVR12 were observed in cirrhotic coinfected (93.3%) and monoinfected (94%) patients. The incidence of HCC following SVR12 achievement was 1.9% and 4% in coinfected and monoinfected patients, respectively (p>0.05). Factors independently associated to de novo HCC occurrence were age (increasing years Hazard Ratio [HR]=1.08, 95% CI 1.04-1.12), albumin (decreasing g/dl HR= 3.03, 95% CI=1.46-6.30) and genotype 3 (HR=2.67, 95% CI=1.03-6.96). Occurrence of hepatic decompensation was 9.9% in coinfected and 9.1% in monoinfected patients. Platelet count lower than 100,000 (HR=2.01, 95% CI 1.29-3.12), albumin (decreasing g/dl HR=1.65, 95% CI 1.08-2.54), HCC (HR=1.83, 95% CI 1.02-3.26) and liver decompensation prior to treatment (HR=7.13, 95% CI 4.51-11.27) were independently associated with the appearance of a decompensation event (ascites, hepatic encephalopathy, portal hypertensive gastrointestinal bleeding) after SVR12. Conclusion. These real life data confirm the high effectiveness of DDA treatment in achieving SVR in advanced liver disease patients, despite HIV coinfection. HIV coinfection is not associated with a higher probability of developing liver complications in HCV-infected patients with advanced liver disease, after viral eradication

Optimization of Hepatitis C Virus screening strategies by birth cohort in Italy

Background: Cost-effective screening strategies are needed to make Hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost-effective in Italy, a high endemic country. Methods: An economic impact model was developed to quantify medical costs and health effects associated with HCV, denominated in quality-adjusted life years (QALYs). The model-estimated prevalence of undiagnosed HCV was used to calculate the number of antibody screens needed annually, with a €25,000 cost-effectiveness threshold. Outcomes over 2018–31 were assessed under the status quo and a scenario that met the World Health Organization’s targets for elimination of HCV. The elimination scenario was assessed under five screening strategies, including universal screening and birth cohort screening. Results: A graduated birth cohort strategy (screening 1968–48 birth cohorts first before expanding to 1968– 88 cohorts) was the least costly. This strategy would gain 143,929 QALYs by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7%, and 88.7% reduction for inversed graduated screening, 1948–77 birth cohort, 1958–77 birth cohort, and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost effectiveness ratio (ICER) of €3,552 per QALY. Conclusion: In Italy, a graduated screening scenario is the most cost-effective strategy. Other countries could consider this approach when developing screening strategies based on specific HCV epidemiology

Optimization of hepatitis C virus screening strategies by birth cohort in Italy

Background and Aims: Cost-effective screening strategies are needed to make hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost-effective in Italy. Methods: A model was developed to quantify screening and healthcare costs associated with HCV. The model-estimated prevalence of undiagnosed HCV was used to calculate the antibody screens needed annually, with a €25 000 cost-effectiveness threshold. Outcomes were assessed under the status quo and a scenario that met the World Health Organization's targets for elimination of HCV. The elimination scenario was assessed under five screening strategies. Results: A graduated birth cohort screening strategy (graduated screening 1: 1968-1987 birth cohorts, then expanding to 1948-1967 cohorts) was the least costly. This strategy would gain approximately 144 000 quality-adjusted life years (QALYs) by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7% and 88.7% reduction for inversed graduated screening, 1948-77 birth cohort, 1958-77 birth cohort and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost-effectiveness ratio (ICER) of €3552 per QALY gained. Conclusions: In Italy, a graduated screening scenario is the most cost-effective strategy. Other countries could consider a similar birth cohort approach when developing HCV screening strategies