Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions.

Contains fulltext : 118153.pdf (Publisher’s version ) (Open Access) Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted dr…

Análisis coste-utilidad de la triple terapia con telaprevir en pacientes con hepatitis C no tratados previamente

Introducción: En España, con una prevalencia del 2,5%, la hepatitis C (VHC) se asocia a una elevada morbi-mortalidad. El tratamiento combinado de telaprevir y peginterferon/ribavirina ([T/PR]) es eficaz en pacientes con VHC-G1. El objetivo primario de este estudio fue evaluar la relación coste-utilidad (RCUI) de [T/PR] versus peginterferon alfa 2a/ribavirina ([PR]) en pacientes naïve VHC-G1, según el grado de fibrosis y bajo la perspectiva del sistema sanitario español. Metodología: La eficacia y la incidencia de efectos adversos (EAs) se obtuvieron de los estudios ADVANCE y OPTIMIZE. La estimación de los costes de monitorización, de manejo de EAs y de la enfermedad por estados de salud (€,…

Advancing the global public health agenda for NAFLD: a consensus statement

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Cost effectiveness of peginterferon α-2b plus ribavirin versus interferon α-2b plus ribavirin for initial treatment of chronic hepatitis C

Background: Peginterferon α-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. Aims: To estimate the cost effectiveness of treatment with peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. Methods: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We u…

Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study

PubMed: 29599078

High efficacy and safety of triple therapy in HCV genotype 1 and moderate fibrosis: a multicenter study of clinical practice in Spain.

Background and rational. Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220). Results. The mean patient age was 55 years, 67% male. Type of prior response was 22% naive, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%)…

Eliminación de la hepatitis C. Documento de posicionamiento de la Asociación Española para el Estudio del Hígado (AEEH)

La Asociación Española para el Estudio del Hígado (AEEH) está convencida de que la eliminación de la hepatitis C en España es posible siempre y cuando seamos capaces de emplear los recursos y las herramientas necesarias para la misma. Este documento refleja la posición de la AEEH respecto a la eliminación del virus de la hepatitis C (VHC), estableciendo una amplia serie de recomendaciones que se pueden agrupar en cinco categorías: 1) cribado del VHC en función de la edad, de la existencia de factores de riesgo clásicos de adquisición de la infección, búsqueda activa de pacientes diagnosticados con anterioridad y desarrollo de estrategias de microeliminación en poblaciones vulnerables; 2) si…

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

HCV elimination; Mental health disorders; Sofosbuvir/velpatasvir Eliminación del VHC; Trastornos de salud mental; Sofosbuvir/velpatasvir Eliminació del VHC; Trastorns de salut mental; Sofosbuvir/velpatasvir Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 w…

Safety and efficacy of a fixed-dose combination regimen of grazoprevir, ruzasvir, and uprifosbuvir with or without ribavirin in participants with and without cirrhosis with chronic hepatitis C virus genotype 1, 2, or 3 infection (C-CREST-1 and C-CREST-2, part B): two randomised, phase 2, open-label trials

Background There is a need for hepatitis C virus (HCV) therapies with excellent efficacy across genotypes and in diverse populations. Part A of the C-CREST-1 and C-CREST-2 trials led to the selection of a three-drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK-8408; an NS5A inhibitor; 60 mg/day) plus uprifosbuvir (MK-3682; an HCV NS5B polymerase inhibitor; 450 mg/day). Part B of the studies tested this combination as a single formulation in different treatment durations in a broader population. Methods Part B of these randomised, phase 2, open-label clinical trials enrolled individuals from 15 countries who were chronically infected with H…

The impact of direct acting antivirals on hepatitis C virus disease burden and associated costs in four European countries

Eliminació del VHC; Punt d'equilibri; Infecció d'hepatitis C Eliminación del VHC; Punto de equilibrio; Infección de hepatitis C HCV elimination; Break-even; Hepatitis C infection Background and Aims We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain. Methods An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus di…

Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020

Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published …

Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study

BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects. AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls. METHODS Prospective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clin…

Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response

Background HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12. Methods This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simepre…

An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

Background: Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12. Methods: In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA 12-week regimen. Conclusions: Overall SVR12 rate (66%) was below the target of 80%, indicating that sho…

P0792 : Baseline factors associated with increased SVR rates in 123 treatment-naïve chronic HCV genotype 1 patients treated with a shortened 12-week simeprevir plus pegylated interferon and ribavirin regimen: a multivariate analysis

PTH-137 Safety and efficacy of simeprevir (SMV) plus PEG-IFN/RBV in treatment-naÏve chronic hepatitis c genotype 1 patients eligible for 12 weeks of treatment

Introduction HPC3014 is a Phase 3, open-label study to assess if response to SMV+Peg-IFN/RBV at Week 2 can allow shortening of treatment to 12 weeks, irrespective of baseline and on-treatment factors. Method Treatment-naive chronic HCV G1-infected patients with no-to-moderate fibrosis (METAVIR F0–F2) were recruited. In patients with HCV-RNA ® Taqman ® lower limit of quantification: 25 IU/mL, lower limit of detection: 15 IU/mL]) at Week 2 and undetectable at Weeks 4 and 8, all treatments were stopped at Week 12 (12-week group). If these criteria were not met, Peg-IFN/RBV was continued to Week 24 (in one case extended to Week 48). Results 123/163 (76%) patients treated were eligible for the 1…

Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study

Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 201…

One‐quarter of chronic hepatitis D patients reach HDV‐RNA decline or undetectability during the natural course of the disease

BACKGROUND Spontaneous HDV-RNA fluctuations, assessed by nonstandardised in-house assays, have been reported during the course of chronic hepatitis delta (CHD). AIMS To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers. METHODS A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined. RESULTS Most participants were male, middle-aged, white European, and HBeAg-negative (82%). Almost half had liver cir…

Guía de tratamiento de la infección por virus de la hepatitis C. Asociación Española para el Estudio del Hígado (AEEH)

The case for simplifying and using absolute targets for viral hepatitis elimination goals

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes …

Análisis coste-utilidad de la triple terapia con telaprevir en pacientes con hepatitis C no tratados previamente

Introducción: En España, con una prevalencia del 2,5%, la hepatitis C (VHC) se asocia a una elevada morbi-mortalidad. El tratamiento combinado de telaprevir y peginterferon/ribavirina ([T/PR]) es eficaz en pacientes con VHC-G1. El objetivo primario de este estudio fue evaluar la relación coste-utilidad (RCUI) de [T/PR] versus peginterferon alfa 2a/ribavirina ([PR]) en pacientes naïve VHC-G1, según el grado de fibrosis y bajo la perspectiva del sistema sanitario español. Metodología: La eficacia y la incidencia de efectos adversos (EAs) se obtuvieron de los estudios ADVANCE y OPTIMIZE. La estimación de los costes de monitorización, de manejo de EAs y de la enfermedad por estados de salud (€,…