RESUMEN
OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.
Asunto(s)
Enfermedad Hepática en Estado Terminal , Hepatitis B , Niño , Humanos , Inmunización Secundaria , Anticuerpos contra la Hepatitis B , Índice de Severidad de la Enfermedad , Hepatitis B/prevención & control , Cirrosis Hepática/complicaciones , Vacunas contra Hepatitis BRESUMEN
OBJECTIVES: To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. METHODS: Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. RESULTS: We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. CONCLUSIONS: One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.
Asunto(s)
Farmacorresistencia Viral , Hepacivirus , Ácidos Aminoisobutíricos , Antivirales/farmacología , Antivirales/uso terapéutico , Bencimidazoles , Ciclopropanos , Genotipo , Alemania/epidemiología , Hepacivirus/genética , Humanos , Italia/epidemiología , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prevalencia , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , Retratamiento , Estudios Retrospectivos , España , Sulfonamidas , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51 ± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.
Asunto(s)
Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Antivirales/efectos adversos , Carbamatos/efectos adversos , Combinación de Medicamentos , Farmacorresistencia Bacteriana/genética , Femenino , Genotipo , Hepacivirus/patogenicidad , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/virología , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/genética , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , España , Respuesta Virológica Sostenida , Factores de Tiempo , Resultado del Tratamiento , Carga ViralAsunto(s)
Anabolizantes/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Mesterolona/efectos adversos , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Pancreatocolangiografía por Resonancia Magnética , Doping en los Deportes , Hospitalización , Humanos , MasculinoAsunto(s)
Agonistas Adrenérgicos/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Norepinefrina/uso terapéutico , Circulación Esplácnica/efectos de los fármacos , Terlipresina/uso terapéutico , Vasoconstrictores/uso terapéutico , Albúminas/uso terapéutico , Diarrea/inducido químicamente , Sustitución de Medicamentos , Femenino , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/cirugía , Hernia Umbilical/cirugía , Herniorrafia , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Trasplante de Hígado , Persona de Mediana Edad , Midodrina/uso terapéutico , Octreótido/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Terlipresina/efectos adversosAsunto(s)
Carcinoma Hepatocelular/terapia , Embolización Terapéutica/efectos adversos , Neoplasias Hepáticas/terapia , Pancreatitis Aguda Necrotizante/terapia , Carcinoma Hepatocelular/complicaciones , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Pancreatitis Aguda Necrotizante/complicacionesRESUMEN
BACKGROUND AND AIMS: Rapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight is the most important source of vitamin D and shows seasonal variation, we evaluated the effect of season on viral kinetics during peginterferon/ribavirin-based therapy for HCV. METHODS: Consecutive HCV patients treated with peginterferon/ribavirin and boceprevir/ telaprevir (June 2011-July 2014) were included. Patients were grouped according to season when therapy was initiated (Season A: May-October and Season B: November-April) depending on hours of daily sunlight. Multiple logistic regression analysis included factors known to influence SVR to treatment. The dependent variables were undetectable viral load (VL) or VL ≤15â UI/mL (VL ≤15) at weeks 4, 8 and 12, end of treatment and SVR. RESULTS: The study included 930 patients (66.8% men; median 54â years) treated with telaprevir (n=537) or boceprevir, without (n=481) or with lead-in therapy of peginterferon/ribavirin. Baseline characteristics of patients in Season A (45.3%, n=421) and Season B groups were similar. Overall, a higher rate of RVR (23.5% vs 16.1%, p=0.005) and VL ≤15 (51.0% vs 38.6%, p≤0.001) was observed in patients starting treatment during Season A versus Season B. By logistic regression analysis, initiating treatment in Season A proved to be an independent predictor of RVR and VL ≤15. CONCLUSIONS: In our setting, seasonality affects viral kinetics in HCV genotype 1 patients treated with peginterferon/ribavirin-based therapy. Our findings support the hypothesis that vitamin D influences viral response to peginterferon/ribavirin-based therapy.
RESUMEN
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO2) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan ((99m)Tc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.
Asunto(s)
Síndrome Hepatopulmonar/etiología , Cirrosis Hepática/complicaciones , Angiografía , Análisis de los Gases de la Sangre , Disnea/etiología , Ecocardiografía , Síndrome Hepatopulmonar/diagnóstico por imagen , Síndrome Hepatopulmonar/epidemiología , Síndrome Hepatopulmonar/fisiopatología , Humanos , Cirrosis Hepática/cirugía , Trasplante de Hígado , Pulmón/diagnóstico por imagen , Oximetría , Imagen de Perfusión , Prevalencia , Radiografía Torácica , Cintigrafía , Radiofármacos , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada por Rayos XRESUMEN
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