Recapture of patients with an incomplete diagnosis of hepatitis C virus infection.

BACKGROUND: hepatitis C virus (HCV) antibody tests have been performed since the 90s, although HCV-RNA (viral load) determination was not always performed. Some of these patients may be actively infected and not be aware of it. Here, we describe a procedure to capture these subjects and complete their diagnosis. METHODS: the historical laboratory results of Navarra were reviewed and individuals who were positive for antibodies against HCV (anti-HCV) and had not undergone HCV-RNA testing were identified. In September 2018, each general practitioner (GP) was informed about their patients and given precise instructions for completing the diagnosis. The procedure was assessed until December 2019. RESULTS: two hundred and eighty-nine anti-HCV positive patients were detected for whom active infection had not been discarded. Two were HIV-positive and six had already died. GPs were asked to assess the remaining 281 subjects. By the end of 2019, a new blood test had been performed in 187 (67 %) patients, 5 % decided not to do it, 4 % were living outside of Navarra, 3 % could not be contacted and the GP considered that it was not justified in 2 % of cases. Thus, 19 % remained to be contacted. From the 187 assessed patients, active infection was confirmed in 52 (28 %) individuals, 40 % were false positives and HCV-RNA was undetectable in 31 %. Regarding the 52 actively infected subjects, 34 had already initiated antiviral therapy and three were hospitalized due to decompensated cirrhosis, from which one patient died. CONCLUSIONS: the strategy to recapture individuals with an incomplete HCV infection diagnosis was effective to detect active infections and subsequent initiation of antiviral therapy.

Health-related quality of life in hepatitis C patients who achieve sustained virological response to direct-acting antivirals: a comparison with the general population.

PURPOSE: To compare health-related quality of life (HRQoL) between hepatitis C patients who achieve sustained virological response (SVR) to direct-acting antivirals and a sex- and age-paired sample of the general population. METHODS: HRQoL was evaluated in patients recruited in Navarre, Spain, from May 2016 to April 2017 at baseline and after SVR, using the EQ-5D-5L questionnaire. Both results were compared to those of general population of the same sex and age obtained from the 2011/12 National Health Survey in Spain. Observed/expected (O/E) ratios for health dimensions and differences between O-E in EQ-5D utility and visual analogical scale (VAS) scores were calculated. RESULTS: 206 patients were studied. Before treatment, patients had more problems than the general population in every domain of EQ-5D-5L, except in self-care dimension (O/E = 1.1). After SVR, patients continued having more limitation, especially for usual activities (O/E = 3.1), anxiety/depression (O/E = 2.8) and EQ-5D utility (- 0.086, p < 0.001); however, differences in VAS score between patients and general population disappeared (74.8 vs 76.5, p = 0.210). F0-F1 patients with SVR had minor differences with the general population in EQ-5D-5L dimensions, utility and VAS score. Although cirrhotic patients also reduced that difference, they still had worse HRQoL, especially in usual activities, self-care, EQ-5D utility (- 0.152, p < 0.001) and VAS score (- 8.5, p = 0.005). CONCLUSIONS: HRQoL of chronic hepatitis C patients remains lower than that of the general population despite viral clearance, with primary problems in usual activities and anxiety/depression. Knowledge of these on-going problems despite cure serves to guide healthcare interventions and patient's follow-up.

Long-term changes on health-related quality of life in patients with chronic hepatitis C after viral clearance with direct-acting antiviral agents.

BACKGROUND AND AIM: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up. METHODS: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL. RESULTS: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05). CONCLUSIONS: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs.

Economic evaluation of a population strategy for the treatment of chronic hepatitis C with direct-acting antivirals.

The high initial cost of antivirals against hepatitis C prompted development of the "Strategic Plan for Tackling Chronic Hepatitis C in the Spanish National Health System". The objective of this study was the economic evaluation of the first two years of its application in Navarre, Spain. The change in the natural history of hepatitis C produced by the sustained virological response (SVR) was compared to an alternative without treatment and modeled with patient-level data. By means of a discrete events simulation model, the cost-effectiveness and the budget impact analysis of the treatment program were measured from the perspective of the Navarre Health Service. Of 656 patients treated, 98% had SVR. The average cost of the treatments was 18,743 euros per patient. The incremental cost-effectiveness ratio (ICER) with discount was 5,346 euros per quality-adjusted life years, which became more efficient as the stage of fibrosis increased until it reached levels of dominance in stage 4 fibrosis. The associated costs for chronic liver disease decreased as the benefit of the treatment was expressed. The implementation of the Strategic Plan is cost-effective, with an ICER well below the threshold, since the cost of treatment is largely compensated by savings in long-term health expenditure. The budgetary impact foresees a net saving from the third year on. The two key parameters were the decrease in the price of the treatment and the SVR in nearly 100% of the patients.

Cost-effectiveness analysis of sofosbuvir-based regimens for chronic hepatitis C.

BACKGROUND: A new scenario of therapy for chronic hepatitis C (CHC) is being established with the approval of sofosbuvir (SOF). OBJECTIVE: To estimate the cost-effectiveness of SOF-based regimens approved in the Summary of Product Characteristics (SmPC) versus the standard of care for different genotypes and patient populations (naive or pretreated). METHODS: A Markov model simulating CHC progression was used to estimate disease treatment costs and effects over patients' lifetimes, from the Spanish National Public Healthcare System perspective. Different therapeutic options were analysed for genotypes 1, 2 and 3 in naive population and for genotype 2 and 3 pretreated patients, according to data obtained from clinical trials. A one-way sensitivity analysis was performed to evaluate the uncertainty of certain parameters: treatment starting age, transition probabilities, drug costs and discount rate. A probabilistic sensitivity analysis was also carried out. RESULTS: For the naive population, the option SOF+pegylated-interferon-α (pIFN)+ribavirin (RBV) for 12 weeks recorded in SmPC for genotype 1 and 3 versus pIFN+RBV for 24 weeks estimated an incremental cost-effectiveness ratio (ICER) below the €40,000/quality-adjusted life-year (QALY) benchmark. For the pretreated population, SOF triple therapy reached an ICER on the threshold limit for genotype 3. Other options included in SmPC for different genotypes exceeded the accepted efficiency limit in our setting. CONCLUSIONS: The options that included SOF+RBV+pIFN in a 12-week course regimen fell below the efficiency threshold considered in our setting. IFN-free regimens administered for 24 weeks reached figures over the benchmark of €40,000/QALY.

Cost-Utility Analysis of Prostatic Artery Embolization for Treatment of Lower Urinary Tract Symptoms.

PURPOSE: To perform a post hoc cost-utility analysis of a randomized controlled clinical trial comparing prostatic artery embolization (PAE) and transurethral resection of the prostate (TURP) in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: We conducted a cost-utility analysis over a 5-year period to compare PAE versus TURP from a Spanish National Health System perspective. Data were collected from a randomized clinical trial performed at a single institution. Effectiveness was measured as quality-adjusted life years (QALYs), and an incremental cost-effectiveness ratio (ICER) was derived from the cost and QALY values associated with these treatments. Further sensitivity analysis was performed to account for the impact of reintervention on the cost-effectiveness of both procedures. RESULTS: At the 1-year follow-up, PAE resulted in mean cost per patient of €2904.68 and outcome of 0.975 QALYs per treatment. In comparison, TURP had cost €3846.72 per patient and its outcome was 0.953 QALYs per treatment. At 5 years, the cost for PAE and TURP were €4117.13 and €4297.58, and the mean QALY outcome was 4.572 and 4.487, respectively. Analysis revealed an ICER of €2121.15 saved per QALY gained when comparing PAE to TURP at long-term follow-up. Reintervention rate for PAE and TURP was 12% and 0%, respectively. CONCLUSIONS: Compared to TURP, in short term, PAE could be considered a cost-effective strategy within the Spanish healthcare system for patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. However, in long term, the superiority is less apparent due to higher reintervention rates.

Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal.

OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS: In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS: Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION: With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Clinical course of patients with severe COVID-19 pneumonia treated with remdesivir: A real-life study.

BACKGROUND: There is currently much uncertainty regarding the most optimal treatment for COVID-19. This study analyze the change in the clinical condition of patients hospitalized for severe COVID-19 pneumonia and treated with remdesivir in a real-life setting, based on the WHO Ordinal Scale. Clinical complications, treatment safety, and impact of other associated drugs were also analyzed. METHODS: We conducted an observational, retrospective study including patients treated with remdesivir. The need for admission to the ICU, the length of ICU and hospital stay, and the need for ventilatory support were analyzed. The laboratory parameters, drugs administered concomitantly, and difference in the length of hospital stay according to the concomitant treatment received were also evaluated. A univariate and multivariate Cox regression analysis was performed to analyze associated factors. RESULTS: A total of 92 patients were included. The mean length of hospital stay was 15 days, and 90% of the patients had been discharged from the hospital 28 days after starting treatment with remdesivir. The likelihood of hospital discharge among patients not presenting with hypertension as a comorbidity was significantly higher than that of those with this condition (HR = 3.19, P = 0.008). Nineteen patients had to be admitted to the ICU (mean of 18 days). Approximately 11% required invasive mechanical ventilation (mean of 22 days). Almost 37% of the patients received high-flow oxygen therapy and 14% non-invasive mechanical ventilation. Four deaths were recorded within the first week. Main adverse events were increases in transaminase and creatinine levels. Nosocomial infections were more frequent when remdesivir was combined with immunosuppressive drugs. CONCLUSIONS: Patients with severe COVID-19 pneumonia and treated with remdesivir require relatively prolonged hospital stays, many with a need for ventilatory support and, in a considerable proportion of cases, admission to the ICU. However, the observed survival rate is high, and the drug is well tolerated.

Survival and clinical events related to end-stage liver disease associated with HCV prior to the era of all oral direct-acting antiviral treatments.

Background: The aim of this study was to describe the natural long-term course of end-stage liver disease associated with chronic hepatitis C (HCV) infection by measuring survival and complication rates in the era prior to the arrival of new direct-acting antiviral (DAA) drugs. Methods: A retrospective population-based cohort study was designed to establish the follow-up of patients hospitalized for a decompensated cirrhotic event or hepatocellular carcinoma using electronic records from hospital discharge databases from 2009 to 2015. Their survival was compared with a sex, age and non-liver mortality excess matched simulation of the general Spanish population. Results: A total of 253 patients were included in the study. Among those with decompensated cirrhosis (n = 151) the hospital admission rate was 1.88 per patient-year with a mortality rate of 0.16 per patient-year. Mean survival was 4.10 years for patients with decompensated cirrhosis, and 1.75 for non-transplanted hepatocellular carcinoma, compared to 18.39 years for the general population. Conclusion: Our results show the complexity and rapid progression of end-stage liver disease associated with HCV infection. The considerable loss of life expectancy associated with the development of decompensated cirrhosis in patients with chronic HCV infection in the absence of viral clearance through treatment is acutely evident.

Impact of successful treatment with direct-acting antiviral agents on health-related quality of life in chronic hepatitis C patients.

BACKGROUND: Direct-acting antivirals (DAA) have demonstrated high efficacy to achieve sustained virological response (SVR) in chronic hepatitis C patients. We aim to assess the change in health-related quality of life (HRQoL) among patients successfully treated, and to identify predictors of this variation. METHODS: In a prospective observational study, patients with chronic hepatitis C who started DAA therapy between May 2016 and April 2017 completed the EQ-5D-5L questionnaire at baseline and 12 weeks after the end of therapy before knowing the virological result. Analysis included all patients with SVR. RESULTS: Median baseline EQ-5D-5L scores of the 206 enrolled patients were 0.857 utility and 70.0 visual analogue scale (VAS). Following SVR, a reduction occurred in the proportion of patients with mobility problems (35% vs 24%, p = 0.012), pain/discomfort (60% vs 42%, p<0.001) and anxiety/depression (57% vs 44%, p = 0.012), with an increase in utility (+0.053, p<0.001) and VAS (+10, p<0.001). Score improvements were also observed in cirrhotic (+0.048 utility, p = 0.027; +15 VAS, p<0.001) and HIV co-infected patients (+0.039 utility, p = 0.036; +5 VAS, p = 0.002). In multivariate analyses, middle age (45-64 years) and baseline anxiety/depression were associated to greater improvement in utility after SVR, and moderate-advanced liver fibrosis and cirrhosis to greater increase in VAS score. Low baseline values were associated to greater improvements in utility value and VAS score. CONCLUSIONS: The cure of chronic hepatitis C infection with DAA has a short term positive impact on HRQoL with improvement in mobility, pain/discomfort, anxiety/depression, utility value and VAS score. Patients with poor baseline HRQoL were the most beneficed.

Comorbidities and cardiovascular risk factors in an aged cohort of HIV-infected patients on antiretroviral treatment in a Spanish hospital in 2016.

OBJECTIVES: The increased survival of HIV-infected individuals has resulted in a premature aging of this population, with the consequent development of premature age-related comorbidities and risk factors. We aimed to describe the prevalence of age-related comorbidities and cardiovascular risk factors in older adults with HIV infection on antiretroviral therapy (ART). METHODS: A retrospective cross-sectional study was undertaken in a cohort of HIV patients aged ≥50 years on ART in September 2016 in Spain. The prevalence of comorbidities (liver cirrhosis, respiratory diseases, cancer, cardiovascular, diabetes, and kidney and bone disorders) and risk factors (smoking, dyslipidemia, and arterial hypertension) was captured. RESULTS: Among the 339 patients included in the study, any comorbidity was present in 52%, the most common being cirrhosis (19%), chronic lung disease (13%), and diabetes mellitus (11%). Over three quarters (78%) had any risk factor: dyslipidemia (55%) and smoking (44%). A higher prevalence of cardiovascular disease was seen in patients ≥60 years in comparison to those aged 50-59 years (23% vs 8%, p = 0.001). Of all study patients, 44% took more than three drugs in addition to their ART, while 29% received no additional pharmacological interventions. CONCLUSIONS: Comorbidities and risk factors for chronic diseases are very common in HIV-infected patients aged ≥50 years and increase with age, so they should be early considered in the clinical management of these patients. It is important to encourage healthy lifestyles to prevent comorbidities and to control risk factors. Concomitant treatments with ART should be carefully monitored to prevent drug interactions, adverse effects, and patient adherence failures.

Progress in the elimination of hepatitis C virus infection: A population-based cohort study in Spain.

BACKGROUND: The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficulties in the elimination of HCV infection in Navarra, Spain. METHODS: Using electronic healthcare databases, we performed a population-based prospective cohort study to describe changes in the prevalence of diagnosed active HCV infection at the beginning of 2015 and the end of 2017, the rate of new diagnoses and the rate of post-treatment viral clearance (PTVC) during this period. RESULTS: At the beginning of 2015 there were 1503 patients diagnosed with positive HCV-RNA, 2.4 per 1000 inhabitants, and at the end of 2017 the prevalence had decreased by 47%. In the study period, 333 (18 per 100,000 person-years) new positive HCV-RNA cases were detected, but only 76 (23%; 4.2 per 100,000 person-years) did not have anti-HCV antibodies previously detected. Prevalent cases and new diagnoses of active infection were more frequent in men, people born in 1950-1979, HIV-infected patients and in those with lower income levels. Among patients with HCV-RNA, 984 achieved PTVC (22.7 per 100 person-years). PTVC was less frequent in patients born before 1940, in immigrants and in patients with lower income levels. CONCLUSIONS: The prevalence of diagnosed active HCV infection has dropped by almost half over three years, because the number of patients with PTVC was much higher than the number of new diagnoses. Interventions specifically targeted at population groups with less favourable trends may be necessary.

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

BACKGROUND: This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. METHODS: A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. RESULTS: Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. CONCLUSION: Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

Safety of oral direct acting antiviral regimens for chronic hepatitis C in real life conditions.

OBJECTIVES: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions. METHODS: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA. RESULTS: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion. CONCLUSION: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.

Cost-effectiveness analysis of simeprevir with daclatasvir for non-cirrhotic genotype-1b-naïve patients plus chronic hepatitis C.

BACKGROUND: The cost of interferon-free combination therapies remains high to provide widespread access to treatment, regardless of fibrosis stage. AIM: To estimate the cost-effectiveness of simeprevir/daclatasvir (SMV/DCV) therapy in treatment-naïve chronic hepatitis C genotype-1b patients with moderate fibrosis. METHODS: A Markov model was developed to simulate the natural history of chronic hepatitis C progression. The model estimated lifetime healthcare costs and quality-adjusted life-years (QALY) for a cohort of patients from the Spanish National Healthcare System perspective. The cost-effectiveness threshold considered was €40,000/QALY. The treatment strategies analyzed were SMV/DCV, peginterferon/ribavirin/telaprevir, and peginterferon/ribavirin/boceprevir. A sensitivity analysis was carried out. RESULTS: The incremental cost-effectiveness ratios of the SMV/DCV strategy were €23,774/QALY and €28,524/QALY compared with that of telaprevir or boceprevir triple therapy, respectively, for genotype-1b patients with moderate fibrosis. CONCLUSIONS: SMV/DCV combination compared with the standard of care previous to the arrival of second-generation direct-acting antivirals fell below generally accepted willingness-to-pay threshold. Results obtained should be supported by ongoing clinical trials.

[Cost-effectiveness analysis of sofosbuvir-simeprevir regimens for chronic hepatitis C genotype 1 patients with advanced fibrosis]. / Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure the cost-effectiveness of the treatment with simeprevir and sofosbuvir in chronic hepatitis C genotype 1 patients with F3-F4 levels of fibrosis, according to the results of the COSMOS trial. MATERIAL AND METHODS: A Markov model was used to estimate the costs and clinical outcomes from the start of therapy. In the model, the progression was simulated alongside the different health states of the chronic liver disease associated with chronic hepatitis C using whole life as time-horizon. RESULTS: The 12-weeks treatment schemes was below the threshold of €40,000 per quality-adjusted life year. On the contrary, despite the 50% cost reduction, the 24-weeks regimen demonstrated a limited level of efficiency when compared with the willingness to pay used in the Spanish medical literature. CONCLUSIONS: This finding would support the introduction of a flat rate in the price of drugs without taking into account the duration of treatment to ensure that treatment with 24 weeks was efficient.

Sofosbuvir plus simeprevir for the treatment of genotype 1 chronic hepatitis C: a review of evidence.

INTRODUCTION: Sofosbuvir (SOF) with simeprevir (SIM) combination was the first interferon-free regimen that reached optimal results in terms of sustained viral response (SVR). Areas covered: A systematic review of the scientific literature concerning the effects that the SOF/SIM combination had on hepatitis C genotype 1 patients yielded 771 references. After the revision process, four clinical trials and 15 observational studies met the inclusion criteria; in total, these studies involved 5,766 patients. The SVR ranged from 67% to 100% depending on the patients' viral subtype and cirrhosis status. Adverse effects were common, but treatment discontinuation related to drug toxicity occurred in less than 5% of cases. Expert commentary: The SOF/SIM combination exhibits efficacy and tolerability profiles that are similar to those of the other available interferon-free combinations used for non-cirrhotic genotype 1b patients. Meanwhile, for patients with advanced cirrhosis or genotype 1a, this approach cannot be considered a routine treatment option due to the unsatisfactory results.

Cost-effectiveness of protease inhibitor based regimens for chronic hepatitis C: a systematic review of published literature.

The treatment of chronic hepatitis C has experienced a substantial progress with the arrival of Boceprevir and Telaprevir due to the significant increase in sustained viral response. Given the high cost, their approval has been followed by great deal of pharmacoeconomic literature analysing their efficiency. A systematic review of this literature was carried out, evaluating both its results and the methodology employed. 54 references were revised including 11 studies, 6 on naive populations, 3 on pre-treated patients and 2 in both of them. As the clinical heterogeneity of patients influenced sustained viral response, therapy regimens were assessed conditioned to the interleukin 28B polymorphism, the early response to treatment and the level of fibrosis, among other variables. Most of the options evaluated on a naive population presented ICERs below the acceptability threshold. The same occurred in the pre-treated population, where the subgroups analysis is perceived as a methodological limitation.

Cost-effectiveness analysis of triple therapy with protease inhibitors in treatment-naive hepatitis C patients.

BACKGROUND: Chronic hepatitis C is the leading cause of chronic liver disease, representing a significant burden in terms of morbidity, mortality and costs. A new scenario of therapy for hepatitis C virus (HCV) genotype 1 infection is being established with the approval of two effective HCV protease inhibitors (PIs) in combination with the standard of care (SOC), peginterferon and ribavirin. OBJECTIVE: Our objective was to estimate the cost effectiveness of combination therapy with new PIs (boceprevir and telaprevir) plus peginterferon and ribavirin versus SOC in treatment-naive patients with HCV genotype 1 according to data obtained from clinical trials (CTs). METHODS: A Markov model simulating chronic HCV progression was used to estimate disease treatment costs and effects over patients' lifetimes, in the Spanish national public healthcare system. The target population was treatment-naive patients with chronic HCV genotype 1, demographic characteristics for whom were obtained from the published pivotal CTs SPRINT and ADVANCE. Three options were analysed for each PI based on results from the two CTs: universal triple therapy, interleukin (IL)-28B-guided therapy and dual therapy with peginterferon and ribavirin. A univariate sensitivity analysis was performed to evaluate the uncertainty of certain parameters: age at start of treatment, transition probabilities, drug costs, CT efficacy results and a higher hazard ratio for all-cause mortality for patients with chronic HCV. Probabilistic sensitivity analyses were also carried out. RESULTS: Incremental cost-effectiveness ratios (ICERs) of €2012 per quality-adjusted life-year (QALY) gained were used as outcome measures. According to the base-case analysis, using dual therapy as the comparator, the alternative IL28B-guided therapy presents a more favorable ICER (€18,079/QALY for boceprevir and €25,914/QALY for telaprevir) than the universal triple therapy option (€27,594/QALY for boceprevir and €33,751/QALY for telaprevir), with an ICER clearly below the efficiency threshold for medical interventions in the Spanish setting. Sensitivity analysis showed that age at the beginning of treatment was an important factor that influenced the ICER. A potential reduction in PI costs would also clearly improve the ICER, and transition probabilities influenced the results, but to a lesser extent. Probabilistic sensitivity analyses showed that 95 % of the simulations presented an ICER below €40,000/QALY. Post hoc estimations of sustained virological responses of the IL28B-guided therapeutic option represented a limitation of the study. CONCLUSION: The therapeutic options analysed for the base-case cohort can be considered cost-effective interventions for the Spanish healthcare framework. Sensitivity analysis estimated an acceptability threshold of the IL28B-guided strategy of patients younger than 60 years.