RESUMEN
This open-label, randomized study compared the efficacy of a regimen of corticosteroids and tacrolimus (standard therapy group, n = 79) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus (modified therapy group, n = 78) in primary liver transplant recipients. The primary endpoint was biopsy-proven acute rejection (BPAR) at 24 weeks. Secondary endpoints included time to rejection and patient and graft survival. The incidence of BPAR was significantly reduced in the modified therapy group compared to the standard therapy group (11.5% versus 26.6%, respectively, P = 0.017). The time to rejection was significantly shorter in the standard therapy group compared with the modified therapy group (P = 0.044). There was no significant difference between groups in patient or graft survival. Hepatitis C virus-positive patients exhibited no differences from hepatitis C virus-negative patients with respect to the incidence of BPAR. A steroid-sparing regimen of daclizumab, mycophenolate mofetil, and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a standard regimen of tacrolimus and steroids.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Rechazo de Injerto/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Ácido Micofenólico/análogos & derivados , Esteroides/administración & dosificación , Tacrolimus/administración & dosificación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Daclizumab , Quimioterapia Combinada , Femenino , Rechazo de Injerto/epidemiología , Humanos , Inmunoglobulina G/efectos adversos , Inmunosupresores/efectos adversos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Infecciones Oportunistas/epidemiología , Estudios Prospectivos , Esteroides/efectos adversos , Tacrolimus/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Prioritizing the liver transplant waiting list (WL) is subject to great variability. We present the experience of four transplant centers in Andalusia (Southern Spain) with a new consensus model of WL management based on the Model for End-Stage Liver Disease (MELD) score. METHODS: The initial criteria for local prioritizing were: a) cirrhosis with MELD score > or =24, and b) all hepatocellular carcinoma (HCC) admitted to the WL. Fourteen months later new criteria were established: a) cirrhosis with MELD score > or =18, and b) uninodular HCC between 3-5 cm or multinodular HCC (2-3 nodules <3 cm). Access to regional priority was scheduled after three months for patients with cirrhosis or six months for patients with HCC. We analyzed the WL mortality rate, posttransplant survival rate, and overall survival rate over three 14-month periods: A (before implementation of priority criteria), B (initial criteria), and C (current criteria). RESULTS: Priority was given to 36% of recipients in period B and 47% in period C. The WL mortality rate (including removals from WL) was 12.9%, 12.9%, and 10.7% in periods A, B, and C, respectively. One-year graft survival was 79.7%, 72.6%, and 81.2% in the same periods. The overall one-year survival rate for new cases on the WL was 74.9% in period A, 68.6% in period B, and 82.2% in period C. CONCLUSIONS: The allocation system and WL management with the current criteria resulted in lower waiting list mortality without reducing posttransplant survival, leading to better survival for all patients listed.
Asunto(s)
Fallo Hepático/mortalidad , Trasplante de Hígado/mortalidad , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Listas de Espera , Femenino , Humanos , Fallo Hepático/cirugía , Masculino , Modelos Biológicos , EspañaAsunto(s)
Trasplante de Hígado/efectos adversos , Mielinólisis Pontino Central/etiología , Complicaciones Posoperatorias , Electroencefalografía , Femenino , Humanos , Trasplante de Hígado/mortalidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielinólisis Pontino Central/diagnóstico , Mielinólisis Pontino Central/mortalidad , Complicaciones Posoperatorias/diagnósticoRESUMEN
No disponible
Asunto(s)
Masculino , Femenino , Persona de Mediana Edad , Humanos , Mielinólisis Pontino Central/etiología , Trasplante de Hígado/efectos adversos , Cirrosis Hepática/cirugíaRESUMEN
BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.
Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Hígado/efectos de los fármacos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Análisis de Varianza , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Femenino , Humanos , Incidencia , Hepatopatías/epidemiología , Fallo Hepático/inducido químicamente , Fallo Hepático/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Probabilidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , España/epidemiología , Análisis de SupervivenciaRESUMEN
AIM: To compare patients who had biochemical and histological features of chronic autoimmune cholestasis (CAIC) using serological autoantibody profiling. METHODS: Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs), antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens were reviewed according to staging, biliary interface activity, lobular hepatitis, granulomas, cholestasis, and florid ductal lesion. RESULTS: In patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24 (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like, multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in immunological, biochemical, or histopathological features between IIF-AMA(+) patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH-related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or ANA-PBC-related antibodies had higher IgM levels, whereas patients with antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and AIH scores, and higher grades of lobular hepatitis. Overall, three distinct categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC-related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with AIH-related antibodies together with serum PBC markers. CONCLUSION: Since these three groups had immunological, biochemical, and histopathological differences, they ought to be considered as separate clinical subentities rather than as merely AMA(-) or AMA(+) patients with autoimmune cholestasis.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Colestasis/inmunología , Enfermedades Autoinmunes/patología , Colestasis/patología , Enfermedad Crónica , Femenino , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Mitocondrias/inmunologíaRESUMEN
Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.