RESUMEN
INTRODUCTION: This study aimed to compare the correlation between the computed tomography (CT) enhancement rate of the venous to portal venous phase (VP-ER) and the extracellular volume (ECV) fraction with shear-wave ultrasound elastography (USE) findings in patients with liver fibrosis. METHODS: We included 450 patients with clinically suspected liver cirrhosis who underwent triphasic dynamic CT studies and USE. We compared the USE results with the unenhanced CT phase, with enhancement in the hepatic artery phase (HAP), portal venous phase (PVP), and venous phase (VP), and with the ECV fraction and the VP-ER. We also compared the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the ECV fraction and VP-ER with that of the values obtained with USE. RESULTS: The VP-ER was the most highly correlated with the liver stiffness value determined with USE (Pearson's correlation coefficient: r = 0.37), followed by enhancement in the PVP (r = -0.25), CT number on unenhanced CT scans (r = -0.22), the ECV fraction (r = 0.19), enhancement in the VP (r = 0.059), and enhancement in the HAP (r = -0.023) (all p < 0.01). The VP-ER showed a significantly higher AUC than the ECV fraction (0.75 vs 0.62) when the liver stiffness was >15 kPa in USE studies (p = 0.04). CONCLUSION: Compared to the ECV fraction, the VP-ER is more useful for predicting all degrees of liver fibrosis on routine triphasic dynamic CT images. IMPLICATIONS FOR PRACTICE: Although improvement is needed, the VP-ER has a higher diagnostic ability for liver fibrosis than the ECV fraction in clinical practice.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Diagnóstico por Imagen de Elasticidad/métodos , Humanos , Cirrosis Hepática/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Curva ROC , Tomografía Computarizada por Rayos XRESUMEN
The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR12 ) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC0-6 h ) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC0-6 h of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR12 rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log10 HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.
Asunto(s)
Antivirales/efectos adversos , Antivirales/farmacocinética , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/efectos adversos , Imidazoles/farmacocinética , Isoquinolinas/efectos adversos , Isoquinolinas/farmacocinética , Insuficiencia Renal/complicaciones , Sulfonamidas/efectos adversos , Sulfonamidas/farmacocinética , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Carbamatos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Imidazoles/administración & dosificación , Incidencia , Isoquinolinas/administración & dosificación , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Pirrolidinas , Diálisis Renal , Insuficiencia Renal/terapia , Sulfonamidas/administración & dosificación , Respuesta Virológica Sostenida , Resultado del Tratamiento , Valina/análogos & derivadosRESUMEN
We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.
Asunto(s)
Genoma Viral , Hepacivirus/genética , Hepatitis C/fisiopatología , Hepatitis Crónica/fisiopatología , Anciano , Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Hepatitis C/tratamiento farmacológico , Anticuerpos contra la Hepatitis C/análisis , Hepatitis Crónica/sangre , Hepatitis Crónica/tratamiento farmacológico , Humanos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral/análisisRESUMEN
We studied the viral genome of a hepatitis B viral strain isolated from a patient with fulminant hepatitis. The patient was followed from prior to the rise in transaminases until she recovered. The precore and core regions of the viral strains were sequenced before and after the illness via the polymerase chain reaction and subcloning methods. Prior to her clinical illness, a strain with precore wild-type sequence and core mutations corresponding to amino acid residues 77 and 113 was noted in large quantities. With the onset of hepatitis, this core variant completely disappeared. Very low titers of precore and core wild or partial core deletion strains remained 1 month later. The core variants described may have contributed to the severe host immune reaction, fulminant hepatitis and immune-mediated viral clearance. Such variants appeared to have been eliminated, and wild and core-deleted virus that lacked the peculiar mutations remained.
Asunto(s)
Encefalopatía Hepática/virología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/virología , Proteínas del Núcleo Viral/metabolismo , Enfermedad Aguda , Adulto , Secuencia de Bases , ADN Viral/análisis , Femenino , Encefalopatía Hepática/genética , Encefalopatía Hepática/metabolismo , Hepatitis B/genética , Hepatitis B/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Humanos , Datos de Secuencia Molecular , Proteínas del Núcleo Viral/genéticaRESUMEN
Disappearance of the hepatitis B e antigen (HBeAg) typically signals the remission of chronic hepatitis B; however, HBeAg defective variants have been identified in patients with HBeAg negative chronic hepatitis (CH). We studied the changes in the hepatitis B virus (HBV) genome associated with HBeAg clearance in four asymptomatic carriers (ASC) and in four patients with CH. Three ASC had a precore stop codon variant with the core region being wild-type or deleted. The other ASC had wild-type precore and core region. In all ASC, HBV levels were reduced markedly with two ASC converting HBV negative status via polymerase chain reaction. In contrast, patients with CH had continued high titers of HBV. In two patients, the precore region remained wild-type, but the core region contained a cleavage site mutation or was deleted. The precore variant was present in both ASC and CH, perhaps suggesting that it does not significantly influence hepatitis B activity.