RESUMEN
Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.
Asunto(s)
Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Following liver transplantation, acute kidney injury (AKI) and chronic kidney disease occur in 20%-50% and 30%-90% of patients, respectively. Basiliximab, a chimeric monoclonal antibody, is highly effective to prevent rejection in organ transplant recipients, particularly among patients with renal dysfunction who benefit from delayed introduction of calcineurin inhibitors. OBJECTIVE: The objective of this study was to measure the immunosuppressive effect of basiliximab and its impact on renal failure, lengths of hospital and intensive care unit (ICU) stays and prevalence of infection. METHODS: From January 2010 through December 2011, we performed a controlled, nonrandomized study comparing two different immunosuppressive regimens: Group I, 36 transplantation on 34 patients, tacrolimus and corticosteroids de novo with mycophenolate mofetil in cases of renal failure; and Group II, 33 transplantation in 33 patients, corticosteriods and mycophenolate mofetil de novo with basiliximab on day 0 and day 4, and inception of tacrolimus on day 3. RESULTS: Basiliximab patients (Group II) showed a significantly lower incidence of renal failure requiring replacement therapy (3.03% vs 25%; P = .014). The incidence of acute cellular rejection episodes treated with corticosteriod boluses was also significantly lower (3.03% vs 25%; P = .014). Bacterial, fungal, and cytomegalovirus infection rates were lower in Group II, although the differences were not significant. Similarly, Group II patients had an insignificantly shorter average stay in the hospital (25.9 vs 40.06 days) and the ICU (5.9 vs 8.17 days). CONCLUSIONS: Basiliximab administration with delayed introduction of calcineurin inhibitors may be an effective strategy to reduce post-liver transplantation AKI requiring renal replacement therapy.
Asunto(s)
Lesión Renal Aguda/prevención & control , Anticuerpos Monoclonales/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Proteínas Recombinantes de Fusión/uso terapéutico , Lesión Renal Aguda/epidemiología , Corticoesteroides/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Basiliximab , Inhibidores de la Calcineurina , Distribución de Chi-Cuadrado , Enfermedades Transmisibles/epidemiología , Quimioterapia Combinada , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Incidencia , Unidades de Cuidados Intensivos , Tiempo de Internación , Trasplante de Hígado/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Factores de Riesgo , Tacrolimus/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report the case of a liver transplant recipient who developed a "splenic artery steal syndrome" (SASS) successfully treated by partial splenic embolization (PSE). Interestingly, because the patient presented an anatomic variant of the splenic artery (SA) originating from the superior mesenteric artery (SMA), improvement was observed in hepatic artery (HA) flow following PSE that could only be explained by decreased portal perfusion and not by the derivation from the SA.
Asunto(s)
Flujometría por Láser-Doppler , Circulación Hepática , Trasplante de Hígado/efectos adversos , Vena Porta/diagnóstico por imagen , Arteria Esplénica/diagnóstico por imagen , Enfermedades Vasculares/etiología , Adulto , Velocidad del Flujo Sanguíneo , Embolización Terapéutica , Hemodinámica , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/fisiopatología , Humanos , Masculino , Vena Porta/fisiopatología , Flujo Sanguíneo Regional , Arteria Esplénica/anomalías , Arteria Esplénica/fisiopatología , Resultado del Tratamiento , Ultrasonografía , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/terapiaRESUMEN
INTRODUCTION: Population ageing is a main concern under the biosanitary point of view. AIM: To assess the nutritional status of people 65 year-old and older in Cantabria (Spain) METHOD: A total of 1605 persons were studied by means of the MNA (Mini Nutritional Assessment); a) by primary care (59.9% in the unit, and 4.7% at home) and, b) in nursing homes (35.4%). RESULTS: Nutritional score (NS) was 23.4 ± 4.1 for women and 24.4 ± 4 in males (p < 0.001). We emphasize the fact that 22.3% of people studied in the nursing homes were malnourished or at risk of malnutrition, compared with 14.2% of those studied at the unit, and only 3.3% of the home visited elders. The correlation between the value of the NS and the subjective estimation of nutrition status showed a high value (0.65). We emphasize the negative correlation (-0.53) between BNI value and the incidence of skin lesions. CONCLUSION: Our results highlight the importance of identifying malnutrition or its risk in elders in order to prevent the negative consequences of this deficiency.
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Anciano/estadística & datos numéricos , Estado Nutricional , Factores de Edad , Anciano de 80 o más Años , Peso Corporal/fisiología , Femenino , Humanos , Masculino , Desnutrición/epidemiología , Casas de Salud , Evaluación Nutricional , Población , Atención Primaria de Salud , Factores Sexuales , España/epidemiologíaAsunto(s)
Neumonía en Organización Criptogénica/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Hígado , Sirolimus/efectos adversos , Neumonía en Organización Criptogénica/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Recurrent hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) frequently causes allograft failure, because viral aggressiveness has been shown to be increased among immunosuppressed patients. Several studies have reported lower efficacy of antiviral therapy after OLT associated with worse tolerability. The aim of this study was to compare the logarithmic falls in viral loads at 4 and 12 weeks of treatment with pegylated interferon alpha and ribavirin among OLT versus immunocompetent patients. OLT patients (group 1) were recruited from 3 Spanish centers. Two age- and sex-matched controls (group 2) were randomly assigned to each case. We excluded coinfection with human immunodeficiency virus or hepatitis B or cholestatic hepatitis. Among group 1 (n = 66) were 72.7% men with an overall mean age of 52.7 +/- 10.1 years; 90.9% were genotype 1. The mean baseline viral load was 6.0 +/- 0.6 log10 IU/mL, and 19% of patients had cirrhosis. Among group 2 (n = 132) were 72.7% men with an overall mean age of 50.1 +/- 10.1 years; 92.4% were genotype 1. The mean baseline viral load was 5.9 +/- 0.5 log10 IU/mL, and 17% of patients had cirrhosis. There were no significant differences in patient characteristics between the 2 groups. The logarithmic falls in viral loads at 4 weeks of treatment were similar in groups 1 and 2: 2.3 +/- 2.1 vs 2.4 +/- 1.9 log10 IU/mL (P = .49); they were also similar at 12 weeks of treatment: 3.9 +/- 1.9 vs 3.7 +/- 2.4 log10 IU/mL (P = .66). In conclusion, in our study HCV sensitivity to combined antiviral therapy was the same among transplant versus immunocompetent patients.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/prevención & control , Hepatitis C/cirugía , Trasplante de Hígado/efectos adversos , Femenino , Humanos , Inmunocompetencia/efectos de los fármacos , Inmunocompetencia/fisiología , Masculino , Selección de Paciente , Recurrencia , España , Carga ViralRESUMEN
Although multifactorial anemia is common following orthotopic liver transplantation (OLT), the late introduction of sirolimus (SRL) has been associated with high rates of anemia, whose pathogenic mechanisms have not been fully studied. Herein we have described a case of severe anemia in an HIV+ OLT patient who was switched from calcineurin inhibitors (CNI) to SRL due to severe nephrotoxicity. After 22 weeks of SRL, hemoglobin levels dropped 4 g/dL to a nadir of 6.5 g/dL. After discarding other causes for anemia, we concluded that it displayed the features of anemia of a chronic inflammatory state (ACIS): decreased mean corpuscular volume (MCV), low serum iron despite high ferritinemia, and elevated fibrinogen and C-reactive protein (CRP) levels. SRL trough levels were never above the therapeutic range. After blood transfusions and erythropoietin (EPO) use, SRL was maintained within the lower range of therapeutic levels, with significant improvement in renal function. As described among kidney transplant recipients, SRL-related anemia in this HIV+ patient with CNI nephrotoxicity after OLT showed features of ACIS. Blood transfusions and EPO use allowed SRL maintenance.
Asunto(s)
Anemia/inducido químicamente , Calcineurina/deficiencia , Seropositividad para VIH , Inmunosupresores/efectos adversos , Trasplante de Hígado/inmunología , Sirolimus/efectos adversos , Proteínas Adaptadoras Transductoras de Señales , Anemia/complicaciones , Anemia/terapia , Transfusión Sanguínea , Proteína C-Reactiva/metabolismo , Eritropoyetina/uso terapéutico , Humanos , Inflamación/etiología , Hierro/sangre , Masculino , Persona de Mediana Edad , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/complicaciones , Transferrina/metabolismoRESUMEN
BACKGROUND: Patients infected with hepatitis C virus genotype 1 who are true non-responders to previous therapy suffer from a very difficult-to-cure disease. New approaches to treatment are necessary. AIM: To explore the efficacy, pharmacokinetics and safety of fixed-dose induction with peginterferon alpha-2a and ribavirin in this difficult-to-cure population. METHODS: Seventy-five hepatitis C virus genotype 1 true non-responder patients to a previous interferon-based combination regimen were randomised to receive peginterferon alpha-2a 360, 270 or 180 microg/week for 12 weeks, followed by 180 microg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon alpha-2a concentration was measured throughout the study. RESULTS: Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 microg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration-time curve of peginterferon alpha-2a from 0-12 weeks increased in a dose-dependent manner (P < 0.0001) and was associated with the sustained virological response (odds ratio: 1.35; 95% CI: 0.89, 2.06). The three regimens were equally well tolerated. CONCLUSION: Fixed-dose induction of peginterferon alpha-2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non-responder patients.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Antivirales/farmacocinética , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/farmacocinética , Masculino , Persona de Mediana Edad , Polietilenglicoles/farmacocinética , Proteínas Recombinantes , Ribavirina/farmacocinética , Resultado del TratamientoRESUMEN
Hepatic encephalopathy is a reversible state of altered cognition that may occur in patients with acute or chronic liver disease or porto-systemic shunt, and in which known neurological or psychiatric signs may develop. Nitrogenated substances from intestinal digestion reach the brain without being cleared by their passage through the liver due to the presence of porto-systemic shunt. We report two cases of patients with porto-systemic shunt diagnosed with recurrent chronic hepatic encephalopathy refractory to conventional medical treatment. They were satisfactorily treated with shunt embolization using interventionist radiology techniques.
Asunto(s)
Embolización Terapéutica , Encefalopatía Hepática/etiología , Encefalopatía Hepática/terapia , Derivación Portosistémica Quirúrgica/efectos adversos , Radiografía Intervencional , Anciano , Femenino , Humanos , Masculino , Inducción de RemisiónRESUMEN
Cyclosporine has recently been reported to produce in vitro suppression of hepatitis C virus replication driven by blockade of cyclophilins, an effect not shown for tacrolimus. However, the clinical consequence of this in vitro finding have not been well studied in vivo. We compared viral load and fibrosis in transplanted patients receiving monotherapy with tacrolimus or cyclosporine. Patients with recurrent hepatitis C after transplantation were selected from two tertiary centers with the following inclusion criteria: monotherapy with tacrolimus or cyclosporine for more than 12 months before viral load measurement, no antiviral treatment, corticosteroids stopped within 12 months after transplantation. HIV, hepatitis B, and active infection by cytomegalovirus were excluded. Patient characteristics, viral load, and fibrosis were compared by univariate analysis between the cyclosporine and tacrolimus groups. Significant variables, viral load, and fibrosis were included in a multivariate model. Sixty-six patients were included, 46 on tacrolimus and 20 on cyclosporine. Fifty-six were male, and the mean age was 55.3 +/- 10.1 years. Fibrosis (Ishak score) was 3.9 +/- 1.9 in the cyclosporine group and 2.7 +/- 1.9 in the tacrolimus group (P = .019). Viral load (log(10)IU/mL) was 5.8 +/- 0.5 and 5.9 +/- 0.5, respectively (P = .7) and time since liver transplantation was 95.3 +/- 47.7 and 41.1 +/- 16.8 months (P = .0001). In the multivariate model, viral load (P = .65) and fibrosis (P = .24) were not significantly different and only time since transplantation remained significant (P = .0001). In conclusion, viral load was not different in patients with tacrolimus as compared with cyclosporine, and the lower fibrosis observed in the cyclosporine group lacked significance when considered together with time since liver transplantation.
Asunto(s)
Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/cirugía , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Anciano , Femenino , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Trasplante de Hígado/inmunología , Trasplante de Hígado/patología , Masculino , Persona de Mediana Edad , Selección de Paciente , Recurrencia , Carga ViralRESUMEN
Corticosteroid boluses, which are the treatment for acute rejection episodes, have been shown to produce transient increases in viremia. However, their effect on long-term viral load, histological activity index (HAI), and fibrosis has not been well established. The aim of our study was to compare late viral load, HAI, and fibrosis in patients with versus without steroid boluses in the immediate posttransplant period. We analyzed patients transplanted due to hepatitis C virus. Inclusion criteria were: no change in immunosuppression (cyclosporine or tacrolimus with/without mycophenolate); no steroids in the previous 4 months; no antiviral treatment; liver biopsy and viral load determination >12 months after transplantation. Exclusion criteria were HIV, hepatitis B, and active cytomegalovirus infection. Nonparametric tests were used to compare viral load, HAI, and fibrosis (Ishak-score) among patients who received steroid boluses for an acute rejection episode (group 1) versus those who did not (group 2). Among the 48 selected patients were 38 men with the overall mean age of the entire group of 55.6 +/- 10.9 years. The mean period from liver transplantation was 53.25 +/- 33.4 months. Thirty-four (70.1%) were treated with tacrolimus and the rest, cyclosporine. Eleven (22.9%) had and 37 (77.1%) had not received corticosteroid boluses. The viral load was similar in groups 1 and 2 (5.74 +/- 0.54 vs 5.98 +/- 0.53 Log(10) IU per mL, P = .32). Fibrosis was also similar (2.5 +/- 1.6 vs 2.2 +/- 1.7, P = .56). However, HAI was higher in group 1 (7.5 +/- 1.7 vs 6.0 +/- 1.7, P = .026). In conclusion, although long-term viral load was similar in patients who had versus had not received one cycle of steroid boluses, the HAI was significantly higher in the former cohort, but had not resulted in greater fibrosis during the study follow-up.
Asunto(s)
Corticoesteroides/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C/cirugía , Trasplante de Hígado/mortalidad , Carga Viral , Adulto , Anciano , Femenino , Rechazo de Injerto/prevención & control , Hepacivirus/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Análisis de Supervivencia , Factores de TiempoRESUMEN
Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C , Interferón-alfa/uso terapéutico , Trasplante de Hígado/efectos adversos , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Biopsia , Femenino , Estudios de Seguimiento , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/patología , Hepatitis C/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , ARN Viral/análisis , Proteínas Recombinantes , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human immunodeficiency virus (HIV)-coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72 log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5 log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI) 0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.
Asunto(s)
Antivirales/uso terapéutico , Seropositividad para VIH/virología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Femenino , Genotipo , VIH/inmunología , Seropositividad para VIH/metabolismo , Hepacivirus/aislamiento & purificación , Hepacivirus/metabolismo , Hepatitis C/inmunología , Humanos , Interferón alfa-2 , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Polietilenglicoles , Estudios Prospectivos , ARN Viral/metabolismo , Proteínas RecombinantesAsunto(s)
Anticuerpos contra la Hepatitis B/sangre , Vacunas contra Hepatitis B , Hepatitis B/transmisión , Trasplante de Hígado/inmunología , Donantes de Tejidos , Formación de Anticuerpos , Femenino , Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Preemptive therapy required highly predictive tests for CMV disease. CMV antigenemia assay (pp65 Ag) has been commonly used for rapid diagnosis of CMV infection. Amplification methods for early detection of CMV DNA are under analysis. OBJECTIVES: To compare two diagnostic methods for CMV infection and disease in this population: quantitative PCR (qPCR) performed in two different samples, plasma and leukocytes (PMNs) and using a commercial diagnostic test (COBAS Amplicor Monitor Test) versus pp65 Ag. STUDY DESIGN: Prospective study conducted in liver transplant recipients from February 2000 to February 2001. RESULTS: Analyses were performed on 164 samples collected weekly during early post-transplant period from 33 patients. Agreements higher than 78% were observed between the three assays. Optimal qPCR cut-off values were calculated using ROC curves for two specific antigenemia values. For antigenemia >or=10 positive cells, the optimal cut-off value for qPCR in plasma was 1330 copies/ml, with a sensitivity (S) of 58% and a specificity (E) of 98% and the optimal cut-off value for qPCR-cells was 713 copies/5x10(6) cells (S:91.7% and E:86%). Using a threshold of antigenemia >or=20 positive cells, the optimal cut-off values were 1330 copies/ml for qPCR-plasma (S 87%; E 98%) and 4755 copies/5x10(6) cells for qPCR-cells (S 87.5%; E 98%). Prediction values for the three assays were calculated in patients with CMV disease (9 pts; 27%). Considering the assays in a qualitative way, the most sensitive was CMV PCR in cells (S: 100%, E: 54%, PPV: 40%; NPV: 100%). Using specific cut-off values for disease detection the sensitivity, specificity, PPV and NPV for antigenemia >or=10 positive cells were: 89%; 83%; 67%; 95%, respectively. For qPCR-cells >or=713 copies/5x10(6) cells: 100%; 54%; 33% and 100% and for plasma-qPCR>or=1330 copies/ml: 78%, 77%, 47%, 89% respectively. CONCLUSIONS: Optimal cut-off for viral load performed in plasma and cells can be obtained for the breakpoint antigenemia value recommended for initiating preemptive therapy with high specificities and sensitivities. Diagnostic assays like CMV pp65 Ag and quantitative PCR for CMV have similar efficiency and could be recommended as methods of choice for diagnosis and monitoring of active CMV infection after transplantation.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , Trasplante de Hígado , Reacción en Cadena de la Polimerasa/métodos , Antígenos Virales/sangre , Citomegalovirus/genética , Citomegalovirus/fisiología , ADN Viral/sangre , Humanos , Leucocitos/virología , Plasma/virología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , España , Carga Viral , Replicación ViralRESUMEN
Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.
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Adenina/análogos & derivados , Hepatitis B/tratamiento farmacológico , Lamivudine/uso terapéutico , Trasplante de Hígado , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Alanina Transaminasa/sangre , Farmacorresistencia Viral , Femenino , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis B/cirugía , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , SeguridadRESUMEN
The efficacy of pegylated interferon (p-IFN) and ribavirin (RB) in transplant patients is not well known. Chronic hepatitis C evolves in a more aggressive form after transplantation, causing a worse survival. Twenty-one naïve patients with recurrent chronic hepatitis C demonstrated by biopsy were treated for 48 weeks with p-IFN alpha2b (1.5 microg/kg/wk) and RB (>10.6 mg/kg/d). Quantification of RNA was performed (Amplicor Cobas 2.0 Roche) at baseline, 4, 12, 24, 48, and 72 weeks. A qualitative technique was used when quantitative levels were undetectable. At more than 1 year since liver transplantation we did not detect coinfection with human immunodeficiency virus or use steroid treatment. Among the cohort there were 16 men (76.2%). The mean overall age was 52 +/- 12 years. Time from liver transplant to treatment was 1637 +/- 1030 days. They were all infected with genotype 1. Eight patients received cyclosporine and the others tacrolimus. One patient was coinfected with hepatitis B virus and was receiving lamivudine. The mean initial histological activity index was 6.9 +/- 1.5 and fibrosis, 2.52 +/- 1.8 (Ishak). Two patients needed spleen embolization before the treatment. Two patients had to stop the treatment: one due to clinical intolerance, and the other one due to a cholangitis. In 14%, p-IFN doses were adjusted. In 32% RB was adjusted. Five (23.8%) did not respond at 24 weeks. Fourteen (66.7%) showed end-treatment responses but four relapsed at 72 weeks. A sustained viral response was achieved in 9 (42.8%). One patient died due to arterial thrombosis just after completing the treatment.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Trasplante de Hígado , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Biopsia , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Interferón alfa-2 , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Recurrencia , Resultado del TratamientoRESUMEN
AIMS: To determine rates of vascular and biliary duct complications, acute rejection, and graft and patient survival according to function status following liver transplantation. METHODS: We classified 248 consecutive liver transplants performed at the Hospital Ramón y Cajal, Madrid, over a 79-month period according to initial function as primary function (NP) versus dysfunction (PD). The latter group was subdivided into grafts showing primary failure (PF) or inadequate function (IPF). The classes NP and IPF were distinguished according to whether transaminase (GOT or GPT) levels and prothrombin activity were above or below 2000 IU and 50%, respectively. RESULTS: There were 23 (9.3%) patients with PD, of whom 12 (4.8%) showed PF. The incidence of vascular and biliary duct complications was similar in both groups, although acute rejection showed a significant difference (PD 3/23 versus NP 98/225; odds ratio =.18). In contrast, the mean survival rates of the grafts (NP 60.37 versus IPF 39.90 months) or patients (NP 63.02 versus PD 47.10 months) were not significantly different. Only 1- and 3-month graft survival rates significantly differed between the NP and IPF groups (NP 95% versus IPF 63%; P=.03 and NP 89% versus IPF 58%; P=.02, respectively). CONCLUSIONS: Recipients with PD or NP after liver transplant showed no differences in the incidence of vascular or biliary duct complications. These groups did vary, however, in terms of rates of acute rejection episodes. No differences in graft and patient survival rates were observed except a significantly lower graft survival at 1 and 3 months, among patients with inadequate primary function.