RESUMEN
We assessed the broadly used, off-label combination of sofosbuvir, daclatasvir, simeprevir, and ribavirin in direct-acting antiviral-experienced patients, as recommended in current guidelines despite scarce data. After 24 weeks' treatment, sustained virological response 12 weeks after the end of treatment was achieved in 6 patients (60%). Two cirrhotic patients relapsed and 2 discontinued treatment due to serious adverse events.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carbamatos , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Imidazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Pirrolidinas , Recurrencia , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Simeprevir/administración & dosificación , Simeprevir/efectos adversos , Simeprevir/uso terapéutico , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Valina/análogos & derivadosRESUMEN
UNLABELLED: Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated variants (RAVs). To avoid cross-resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This "real-world" study comprised patients who had failed to achieve SVR on previous NS5A-based therapy with daclatasvir (DCV) plus pegylated interferon (Peg-IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post-treatment); on-treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43-73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6-70 kPa; cirrhosis, n = 9); median baseline HCV-RNA level was 1.38 × 10(6) IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (<12 IU/mL) by end of treatment (EOT) and 10 of 16 had a rapid response (week 4). SVR12 was achieved by 14 of 16 patients; the remaining 2 relapsed by 4 weeks post-EOT (both were GT 1a infected with cirrhosis; 1 had previously failed DCV-ASV plus Peg-IFN and RBV). Presence of SIM RAVs/polymorphisms (R155K and Q80K) at study baseline did not predict retreatment failure. CONCLUSION: Our findings support the concept of retreating NS5A inhibitor failures with SOF combined with SIM. However, the most difficult-to-cure patients may need more than 12 weeks of treatment and/or the addition of RBV. (Hepatology 2016;63:1809-1816).
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Carbamatos , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/genética , Humanos , Imidazoles , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pirrolidinas , Respuesta Virológica Sostenida , Insuficiencia del Tratamiento , Valina/análogos & derivadosRESUMEN
BACKGROUND: FibroTest and elastography have been validated as biomarkers of liver fibrosis in the most frequent chronic liver diseases and in the fibrosis screening of patients with diabetes. One challenge was to use them for estimating the prevalence of fibrosis, identifying independent risk factors and to propose screening strategies in the general population. METHODS: We prospectively studied 7,463 consecutive subjects aged 40 years or older. Subjects with presumed advanced fibrosis (FibroTest greater than 0.48) were re-investigated in a tertiary center. RESULTS: The sample characteristics were similar to those of the French population. FibroTest was interpretable in 99.6%. The prevalence of presumed fibrosis was 2.8%, (209/7,463), including cirrhosis in 0.3% (25/7,463); 105/209 (50%) subjects with presumed fibrosis accepted re-investigation. Fibrosis was confirmed in 50, still suspected in 27, indeterminate in 25 and not confirmed with false positive FibroTest or false negative elastography in 3 subjects. False negative rate of FibroTest estimated using elastography was 0.4% (3/766). The attributable causes for confirmed fibrosis were both alcoholic and nonalcoholic fatty liver disease (NAFLD) in 66%, NAFLD in 13%, alcohol in 9%, HCV in 6%, and other in 6%. Factors independently associated (all P < 0.003) with confirmed fibrosis were age, male gender, waist circumference, HCV antibody and alcohol consumption estimated using carbohydrate-deficient transferrin, enabling efficient screening-oriented strategies to be compared and proposed. CONCLUSIONS: Biomarkers have permitted to estimate prevalence of advanced fibrosis around 2.8% in a general population aged 40 years or older, and several risk factors which may be used for the validation of selective or non-selective screening strategies.
Asunto(s)
Biomarcadores/sangre , Cirrosis Hepática/epidemiología , Vigilancia de la Población , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteína A-I/sangre , Bilirrubina/sangre , Diagnóstico Diferencial , Femenino , Francia/epidemiología , Haptoglobinas/metabolismo , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , alfa-Macroglobulinas/metabolismo , gamma-Glutamiltransferasa/sangreAsunto(s)
Elasticidad/fisiología , Insuficiencia Cardíaca/fisiopatología , Venas Hepáticas/fisiopatología , Cirrosis Hepática/diagnóstico , Hígado/irrigación sanguínea , Diagnóstico Diferencial , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Humanos , Hígado/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV. METHODS: In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied. RESULTS: Forty-six percent of patients had fibrosis > or =F2. A positive predictive value of a score >0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of < 0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (< 0.6 and >0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients. CONCLUSION: The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.
Asunto(s)
Biomarcadores/sangre , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/terapia , Trasplante de Riñón/fisiología , Diálisis Renal , Adulto , Automatización , Femenino , Hepatitis C Crónica/patología , Hepatitis C Crónica/cirugía , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría/métodos , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: This study analyzes the biochemical, serological, and virological efficacy and the safety of adefovir dipivoxil in patients with renal disturbances. METHODS: Twelve patients with lamivudine-resistant hepatitis B virus (HBV) chronic infection were treated for a median time of 15 (3-19) months. The daily dosage was 10 mg initially and then adjusted according to renal function. RESULTS: Median (range) ALT values remained stable: 55 (13-117) and 37 (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from 8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No virologic breakthrough was observed. One of the six HBeAg-positive patients lost HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no significant clinical and biochemical adverse effects. In the 11 nonhemodialysed patients, the creatinine clearance significantly improved from 70 (30-100) to 88 (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to 0.12 (0.01-0.74) g/day (NS). CONCLUSIONS: Adefovir dipivoxil is safe for the treatment of chronic hepatitis B in patients with varying degrees of renal dysfunction and lamivudine-resistant HBV and results in biochemical and virological efficacy similar to that reported in the general population.
Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Trasplante de Riñón , Organofosfonatos/uso terapéutico , Diálisis Renal , Insuficiencia Renal/complicaciones , Adenina/efectos adversos , Adenina/farmacocinética , Adenina/uso terapéutico , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/farmacocinética , Farmacorresistencia Viral , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Organofosfonatos/farmacocinética , Viremia/tratamiento farmacológicoRESUMEN
Primary biliary cirrhosis is a chronic cholestatic liver disease of unknown cause that predominantly affects middle-aged women. Distal tubular acidosis is the main renal complication of primary biliary cirrhosis. Tubulointerstitial nephritis and Fanconi syndrome have been reported more rarely. We report on 2 patients with primary biliary cirrhosis who presented with tubulointerstitial nephritis and Fanconi syndrome and review similar cases published previously. Serum from 1 patient exerted an inhibitory effect on pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, 2 mitochondrial enzymes that are the main targets of antimitochondrial antibodies in primary biliary cirrhosis. Antimitochondrial antibodies may have a role in the genesis of tubulointerstitial nephritis and Fanconi syndrome, 2 typical renal features of mitochondrial cytopathies. Tubulointerstitial nephritis and Fanconi syndrome have to be added to the spectrum of renal diseases associated with primary biliary cirrhosis.