RESUMEN
INTRODUCTION: Interferon-based therapies against the hepatitis C virus had a poor adherence profile. On the other hand, new direct-acting antivirals (DAAs) are orally administered medications, show high efficacy against the hepatitis C virus in addition to a high safety profile. Therefore, adherence to this treatment is expected to improve. Assessment for treatment adherence is mandatory to assess the feasibility of achieving viral hepatitis elimination. AIM: The study aims to assess the adherence rate and causes of non-adherence in Egyptian hepatitis C patients who received interferon-free treatment regimens. METHODS: Retrospective data analysis for 668 hepatitis C patient's records from August 2014 to October 2019 was done. Assessment of treatment adherence was done by revising the records and phone calls. However, 172 patients were excluded due to the absence of contact data. Rest of patients (n = 496) was categorized into 2 groups: Adherent (n = 432) and non-adherent (n = 64). For whom comparative analysis was done. RESULTS: The adherent group (87%) achieved 100 % sustained virological response after 12 weeks (SVR 12). Non-adherence was reported in 12.9% of patients. Low awareness was the main cause of non-adherence (43.75%). BMI was the only significant risk factor for poor adherence (P = .04). Other Patient demographics, clinical, and laboratory data didn't show any significant differences between both groups. CONCLUSION: Interferon-free regimens are tolerable. Raising awareness is mandatory for proper treatment adherence and, subsequently, good clinical outcomes.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Quimioterapia Combinada , Egipto , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n = 4,153; I2 = 84.2%) and per-protocol analysis (15 studies; n = 4,833; I2 = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR = 1.03 (0.99-1.07)] and those naive compared with treatment experimented-individuals [9 studies; RR = 1.01 (1.00-1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02-1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].
Asunto(s)
Hepatitis C Crónica , Antivirales/uso terapéutico , Brasil , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
Asunto(s)
Hepatitis C/terapia , Antivirales/uso terapéutico , Consenso , Medicina Basada en la Evidencia , Hepatitis C/tratamiento farmacológico , Humanos , MéxicoRESUMEN
OBJECTIVE: HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. PATIENTS AND METHODS: In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). RESULTS: A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. CONCLUSIONS: HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin (RBV) regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct-acting antiviral (DAA) therapies began with the development of first-generation NS3/4A protease inhibitors in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then, a multitude of DAAs have been licensed for use, and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, RBV-free, and involve a combination of DAA agents. This review summarizes the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C.
RESUMEN
OBJECTIVE: The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens. PATIENTS AND METHODS: From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ. RESULTS: A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and ≥LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004. CONCLUSIONS: TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting.
Asunto(s)
Antivirales/administración & dosificación , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Administración Oral , Antivirales/farmacología , Bencimidazoles/administración & dosificación , Bencimidazoles/farmacología , Carbamatos , Femenino , Fluorenos/administración & dosificación , Fluorenos/farmacología , Genotipo , Hepacivirus/genética , Humanos , Imidazoles/administración & dosificación , Imidazoles/farmacología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pirrolidinas , Ribavirina/administración & dosificación , Ribavirina/farmacología , Sofosbuvir/administración & dosificación , Sofosbuvir/farmacología , Respuesta Virológica Sostenida , Resultado del Tratamiento , Valina/análogos & derivadosRESUMEN
Development of direct acting antivirals has revolutionized the standard of care for the treatment of hepatitis C virus. New interferon-free regimens provide sustained virologic response rates of >90% in many genotype 1 patients with only 12 weeks of oral therapy. This review will provide a brief overview of current standards of care with a summary of the evidence supporting the recommended combinations of direct acting antivirals. We will discuss the direction of future therapies, with strategies for shorter durations of therapy and new all-oral combinations in the pipeline.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Administración Oral , Antivirales/administración & dosificación , Quimioterapia Combinada , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Factores de TiempoRESUMEN
Optimal therapy for patients with hepatitis C virus (HCV) genotype 4 (HCV-4) infection is changing rapidly, and the possibility of a total cure is near. The standard of care has been combination pegylated interferon (PEG-IFN)-ribavirin (RBV), with modest response rates and considerable adverse events. Since the introduction of sofosbuvir (SOF), simeprevir (SIM), and daclatasvir (DCV), the duration of treatment has been significantly shortened and response rates have increased. The recommended treatment for IFN-eligible patients is PEG-IFN/RBV plus SOF, SIM or DCV. In IFN ineligible patients, the optimal regimen is a 24-week course of SOF/RBV, or a 12-week course of SOF-SIM or SOF-DCV with or without RBV. The pipeline for patients with chronic HCV is highly active. IFN-free combinations with paritaprevir-ombitasvir, SOF-ledipasvir, or DCV-asunaprevir (ASV)-beclabuvir (BMS-791325) for 12 weeks or less with close to 100% cure rates will soon become the optimal therapy.
Asunto(s)
Quimioterapia Combinada/tendencias , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Imidazoles/uso terapéutico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Sulfonamidas/uso terapéutico , Uridina Monofosfato/análogos & derivados , Carbamatos , Quimioterapia Combinada/métodos , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/genética , Humanos , Pirrolidinas , Proteínas Recombinantes/uso terapéutico , Simeprevir , Sofosbuvir , Uridina Monofosfato/uso terapéutico , Valina/análogos & derivados , Proteínas no Estructurales Virales/antagonistas & inhibidoresRESUMEN
Current estimates indicate that the hepatitis C virus is the leading cause of death in the United States with infection rates steadily increasing. Successful treatment is made difficult by the presence of various host, virus, and treatment-related factors, warranting the development of new approaches to combat the silent epidemic. The addition of telaprevir and boceprevir to the pharmacotherapeutic arsenal drastically improved success rates in genotype 1 infected patients, but rapid development of resistance mechanisms, increases in adverse effects, and a low spectrum activity proved to be barriers to efficacious treatment. In late 2013, two new agents were approved - sofosbuvir and simeprevir - that have higher barriers to resistance, favorable safety profiles, and profoundly improved success rates; however higher costs associated with the new medications could limit their wider utilization. Further strategies to combat the virus are under development, ranging from interferon-free regimens as well as prophylactic and therapeutic vaccines to applications of nanotechnology, helping us get closer to improved treatment of patients infected with hepatitis C.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Animales , Hepacivirus/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Simeprevir , Sofosbuvir , Sulfonamidas/uso terapéutico , Insuficiencia del Tratamiento , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapéuticoRESUMEN
BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were 60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (37,900/QALY gained), but not at F0-1 (103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.
Asunto(s)
Antivirales/administración & dosificación , Antivirales/economía , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/economía , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Quimioterapia Combinada/economía , Francia , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Interferones/administración & dosificación , Interferones/economía , Interferones/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/economía , Cirrosis Hepática/virología , Persona de Mediana Edad , Modelos Económicos , Oligopéptidos/administración & dosificación , Oligopéptidos/economía , Prolina/administración & dosificación , Prolina/análogos & derivados , Prolina/economía , Años de Vida Ajustados por Calidad de Vida , Ribavirina/administración & dosificación , Ribavirina/economía , Resultado del TratamientoRESUMEN
Therapy for hepatitis C is undergoing a revolution. Several new drugs against the hepatitis C virus (HCV) have reached the market and many others, including direct-acting antivirals and host-targeted agents, are in phase II or III clinical development. All-oral, interferon-free combinations of drugs are expected to cure more than 90% of infections. A vast amount of data from clinical trials are presented regularly at international conferences or released to the press before peer-review, creating confusion in the viral hepatitis field. The goal of this review is to clarify the current stage of HCV therapy and drug development. This review describes the different classes of drugs and their mechanisms and properties, as well as treatment strategies in development, including those that are interferon-based and interferon-free. HCV treatment options that will be available in 2014-2015 are presented for each genotype. A number of unanswered questions and challenges remain, such as how to treat special populations, the role of ribavirin in interferon-free regimens, the role of HCV resistance in treatment failures, and how to best re-treat patients who failed on treatment. Strategic choices, cost issues, HCV screening, and improving access to care in resource-constrained areas also are discussed.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/economía , Países en Desarrollo , Costos de los Medicamentos , Farmacorresistencia Viral , Quimioterapia Combinada , Genotipo , Salud Global , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/economía , Hepatitis C/epidemiología , Humanos , Selección de Paciente , Fenotipo , Prevalencia , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) infection is curable by therapy. The antiviral treatment of chronic hepatitis C has been based for decades on the use of interferon (IFN)-α, combined with ribavirin. More recently, new therapeutic approaches that target essential components of the HCV life cycle have been developed, including direct-acting antiviral (DAA) and host-targeted agents (HTA). A new standard-of-care treatment has been approved in 2011 for patients infected with HCV genotype 1, based on a triple combination of pegylated IFN-α, ribavirin, and either telaprevir or boceprevir, two inhibitors of the HCV protease. New triple and quadruple combination therapies including pegylated IFN-α, ribavirin, and one or two DAAs/HTAs, respectively, are currently being evaluated in Phase II and III clinical trials. In addition, various options for all-oral, IFN-free regimens are currently being evaluated. This chapter describes the characteristics of the different drugs used in the treatment of chronic hepatitis C and those currently in development and provides an overview of the current and future standard-of-care treatments of chronic hepatitis C.