RESUMEN
Liver involvement in SCD patients is frequent but often misdiagnosed or underestimated, except in case of advanced liver diseases. Because of so far poorly recognized forms of chronic SCD-related vascular injury that can silently evolved towards end stages or facilitate ACLF, any persisting liver function tests abnormalities should be carefully investigated, following the above proposed algorithm. Work up and management must be considered multidisciplinary in relationship with a Hepatologist. Early SCD hepatopathy should prompt revision of SCD management to prevent further liver injury and decompensation, discussing transfusion exchanges and hydro urea when not yet initiated, and control for any cofactor of liver injury. The role of HSCT in early SCD hepatopathies also deserves evaluation. In advanced SCD hepatopathies, liver transplantation, which has been rarely performed so far, is the only therapeutic option associated with improved survival. It should definitely be discussed- either electively in case of decompensation in SCD cirrhosis or jaundice/recurrent cholangitis in cholestatic diseases, with excellent outcome, - or emergently in case of ALF or ACLF with more mitigate results. To improve knowledge and management of SCD liver diseases, creation of national and international registries, as well as longitudinal observational cohorts are encouraged.
Asunto(s)
Anemia de Células Falciformes , Hepatopatías , Trasplante de Hígado , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/terapia , Hepatopatías/etiología , Hepatopatías/terapia , Cirrosis Hepática/complicacionesRESUMEN
Data on the conversion of patients to everolimus after liver transplantation are sparse. A multicenter, retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion, the employed regimens and exposure levels, and the impact on efficacy and safety. The mean time from transplantation to the introduction of everolimus was 4.9 ± 5.2 years. The mean everolimus trough level was 7.3 ± 4.1 ng/mL at month 1 and 8.1 ± 4.7 ng/mL at month 12. At 12 months, 61.6% of the patients were no longer receiving calcineurin inhibitor (CNI) therapy. The mean estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault formula was 64.2 ± 30.0 mL/minute on day 0 and 68.4 ± 32.5 mL/minute at month 12 (P = 0.007). Among patients with baseline serum creatinine levels ≥ 130 µmol/L, the eGFR values were 44.3 ± 15.7 mL/minute on day 0 and 53.7 ± 26.0 mL/minute at month 12 (P = 0.003). Four patients (1.6%) developed mild or moderate biopsy-proven acute rejection. Adverse events led to everolimus discontinuation in 12.9% of the patients. After the initiation of everolimus, the mean white blood cell count decreased significantly, and the total cholesterol and triglyceride levels increased significantly. In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus, more than 60% of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile. Randomized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted.
Asunto(s)
Trasplante de Hígado/métodos , Sirolimus/análogos & derivados , Adulto , Anciano , Biopsia , Inhibidores de la Calcineurina , Everolimus , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Sirolimus/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Triglicéridos/metabolismoRESUMEN
Sickle cell disease (SCD) frequently affects the liver; if acute liver failure (ALF) develops, the only potentially effective therapeutic option is liver transplantation (LT). Only 12 patients for whom LT was performed for SCD-related ALF have been described so far. We report a retrospective series of 6 adult patients with SCD (3 men and 3 women, median age = 40.1 years) who underwent emergency LT. The indication for LT was ALF complicating cirrhosis in 5 patients (hepatitis C/iron overload-induced cirrhosis in 3 and iron overload-induced cirrhosis in 2); one patient had autoimmune hepatitis. The median follow-up was 52.7 months (0.5-123 months). The 1-, 3-, 5-, and 10-year survival rates were 83.3%, 66.7%, 44.4%, and 44.4%, respectively. One patient died of hepatocellular failure precipitated by hyperacute allograft rejection on post-LT day 10. Soon after LT, 2 patients developed seizures; in 1 case, the seizures were a complication of early calcineurin inhibitor-induced leukoencephalopathy. Four long-term survivors benefited from specific management of SCD; specifically, the hemoglobin S fraction was maintained below 30% and the total hemoglobin level was maintained between 8 and 10 g/dL. Two patients had mild vaso-occlusive crises. Three patients experienced a recurrence of hepatitis C virus (HCV) infection; 2 of these patients experienced reversible neurological complications while they were receiving antiviral treatment. Carefully selected patients with SCD may benefit from emergency LT. However, such patients seem to be particularly susceptible to neurological complications after LT. In contrast, severe SCD-related crises do not seem to recur if specific management is provided. Outcomes may be improved if the neurological complications can be minimized; for example, the administration of a calcineurin inhibitor can be delayed, and the management of HCV infection recurrence can be improved.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Adulto , Femenino , Humanos , Hígado/patología , Fallo Hepático Agudo/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/PURPOSE: Liver transplantation (LT) is the best theoretical treatment of hepatocellular carcinoma (HCC) fulfilling the Milan criteria (TNM stages 1-2). However, LT is limited by organ availability and tumor progression on the waiting list. Liver resection (LR) may represent an alternative in these patients. The aim of this study is to report the results of LR in transplantable patients. PATIENTS: From 1990 to 2007, 274 patients underwent liver resection for HCC. Sixty-seven (24%) met the Milan criteria on pathologic study of the specimen. Ten were TNM stage 1 and 57 stage 2 and all had chronic liver disease. There were 56 men and 11 women with a mean age of 63. LR included 12 major hepatectomies, 14 bisegmentectomies, 14 segmentectomies, and 27 nonanatomic resections. Thirty-seven resections were performed through a laparoscopic approach and there were only 8 open resections since 1998. RESULTS: Three patients died postoperatively (4.5%), none after laparoscopic resection. Morbidity rate was 34%. After a mean follow-up of 4.8 years, 36 patients (54%) developed intrahepatic tumor recurrence. Twenty-eight (77%) were again transplantable of which 16 (44%) were transplanted. Two additional patients underwent pre-emptive LT (ie before recurrence). When considering 44 patients <65 years at the time of resection (ie upper age limit for LT), the rates of recurrence, transplantable recurrence, and intention to treat salvage transplantation (patients with transplantable recurrence actually transplanted) were 59%, 80%, and 61%, respectively. Overall and disease free 5-year survival rates were 72% and 44%, respectively. Survival was not influenced by TNM stage 1 or 2, AFP level, tumor differentiation, or the presence microscopic vascular invasion. Survival after salvage LT was 70% and 87% when calculated from the date of LT and LR, respectively. CONCLUSION: LR for small solitary HCC in compensated cirrhosis yields an overall survival rate comparable to upfront LT. Despite a significant recurrence rate, close imaging monitoring after resection allows salvage LT in 61% of patients with recurrence on intention to treat analysis.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Hepatitis/complicaciones , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Tacrolimus and cyclosporin inhibits the activity of calcineurin, a serine/threonine phosphatase that is involved in many physiological and pathological pathways. However, the baseline calcineurin phosphatase activity (CPA) measured before the transplant is unknown. In this study, we determine baseline CPA in liver transplant (LT) candidates and explore some factors that might modify it. PATIENTS AND METHODS: Thirty-two consecutive LT candidates (25 men, seven women, average age 53.4 years) were included. Seven millilitres of whole blood was collected from each patient. CPA was determined in lymphocytes quantifying a dephosphorylated peptide phosphorylated previously (D-L-D-V-P-I-P-G-R-F-D-R-R-V-S-V-A-A-E) by high-performance liquid chromatography. The relationship between CPA and the quantitative variables was tested according to Pearson's correlation. A two-way analysis of variance was performed to test the independent role of categorical parameters in CPA. RESULTS: The median CPA was significantly lower in LT candidates than in healthy volunteers [179.2 (146.9-226.3) vs 247.8 (220.9-292.5) pmol/min/10(6) peripheral blood mononuclear cell (PBMC), respectively, P=0.0002]. CPA was also significantly lower in alcoholic cirrhosis (152.2 vs 211.1 pmol/min/10(6) PBMC, P=0.04) and in the presence of hepatocellular carcinoma (HCC) (152.0 vs 213.5 pmol/min/10(6) PBMC, P=0.0074) compared with other liver diseases. A two-way analysis of variance showed that these parameters were independently associated with lower CPA (P=0.05 for alcohol and P=0.0056 for HCC respectively). CONCLUSION: This pilot study showed a lower CPA in patients with AC and HCC. This phenomenon may contribute towards lowering the risk of acute rejection in these patients after LT and, on the other hand, may increase the risk of de novo cancers.
Asunto(s)
Calcineurina/sangre , Carcinoma Hepatocelular/sangre , Cirrosis Hepática Alcohólica/sangre , Neoplasias Hepáticas/sangre , Trasplante de Hígado , Adulto , Anciano , Calcineurina/deficiencia , Carcinoma Hepatocelular/cirugía , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Leucocitos Mononucleares/enzimología , Cirrosis Hepática Alcohólica/cirugía , Pruebas de Función Hepática , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Monoéster Fosfórico Hidrolasas/metabolismo , Proyectos Piloto , Adulto JovenRESUMEN
Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
Asunto(s)
Resistencia a la Insulina , Trasplante de Hígado , Síndrome Metabólico/cirugía , Hígado Graso/patología , Femenino , Estudios de Seguimiento , Humanos , Fallo Hepático/cirugía , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , RecurrenciaRESUMEN
BACKGROUND AND AIMS: Recurrent hepatitis C after liver transplantation (LT) is associated with rapid fibrosis progression. The aim of this study was to evaluate the cumulative risk for severe fibrosis and the factors influencing it. PATIENTS AND METHODS: Two hundred and fifty LT patients were included 1 to 15years after LT. Recurrence of chronic hepatitis C on liver graft was classified according to Metavir score. RESULTS: Kaplan-Meyer estimates for actuarial progression to severe fibrosis (Metavir>F3) showed a probability of 15.2% and 44.5% at 5 and 10years, respectively. Predictive factors for progression to severe fibrosis were: use of tacrolimus as main CNI, recipient age at time of biopsy<55, donor age ≥45, graft HCV re-infection<3months, biologically suspected graft re-infection and lack of response to antiviral treatment after LT. Multivariate analysis disclosed that only donor age ≥45 (hazard ratio 2.243, 95%CI 1.264-3.983, P=0.0058) and lack of response to antiviral treatment (hazard ratio 2.816, 95%CI 1.227-6.464, P=0.0146) were associated to severe fibrosis. CONCLUSIONS: Our study confirms that donor age ≥45 and lack of response to antiviral treatment after LT are major predictive factors of progression of HCV recurrence on liver graft.
Asunto(s)
Hepatitis C Crónica/epidemiología , Cirrosis Hepática/epidemiología , Trasplante de Hígado , Adulto , Factores de Edad , Anciano , Antivirales/efectos adversos , Estudios Transversales , Progresión de la Enfermedad , Resistencia a Medicamentos , Femenino , Francia/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Índice de Severidad de la Enfermedad , Donantes de TejidosAsunto(s)
Trastornos Relacionados con Cocaína/complicaciones , Cocaína/toxicidad , Hepatitis C/complicaciones , Fallo Hepático/cirugía , Adulto , Intoxicación Alcohólica/complicaciones , Estudios de Seguimiento , Humanos , Fallo Hepático/etiología , Masculino , Factores de Tiempo , Resultado del TratamientoRESUMEN
Hepatocellular carcinoma (HCC) is currently the leading indication for liver transplantation in France, accounting for 25% of all cases. Transplantation is appropriate, nonetheless, only for patients whose HCC has a low risk of posttransplant recurrence and is limited in size and number, meeting the Milan criteria (1 single nodule of a maximum diameter of 5 cm or 3 lesions of a maximum diameter of 3 cm), or slightly exceeds these criteria without vascular invasion visible on preoperative imaging. Results for this indication are very satisfactory, and 5-year survival ranges from 60 to 80%, according to tumor stage. Small HCCs (<2 cm) are usually treated conservatively. Transplantation is proposed in cases of a contraindication to resection or radiofrequency ablation or of recurrence after local treatment. A history of an extrahepatic tumor is found in approximately 5% of candidates for liver transplantation. This history is not necessarily a contraindication to transplantation. They may be considered eligible for a graft after discussion in a multidisciplinary meeting, if the extrahepatic tumor was treated curatively and if their 5-year tumor-related life expectancy is greater than 50-60%.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/normas , Recurrencia Local de Neoplasia , Neoplasias Primarias Múltiples , Carcinoma Hepatocelular/patología , Contraindicaciones , Humanos , Huésped Inmunocomprometido/inmunología , Trasplante de Riñón/inmunología , Esperanza de Vida , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/patología , Trasplante de Hígado/mortalidad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/inmunología , Selección de Paciente , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas/cirugía , Carga TumoralRESUMEN
BACKGROUND: The advent of computer-based technology has led to innovative epidemiological research methods to exploit the advantages of computer-mediated communications. The aim of the present study was to develop and evaluate a self-administered electronic questionnaire for acquiring information on cardiovascular health, knowledge and behaviours in a representative, stratified sample of the Italian population. METHODS: We report information on the attitudes and approach to cardiovascular disease prevention in a representative sample of Italian families who were interviewed at home by electronic questionnaires. The panel of families is currently used for national opinion polls and marketing surveys. Electronic questionnaires were filled out by 1683 males and 1736 females during a weekend period. RESULTS: Two-thirds of respondents reported having their blood pressure measured while only half reported having blood lipid and glucose tests over the previous 2 years. Prevalence of reported hypertension, hypercholesterolaemia, diabetes and smoking were 15.2, 13.0, 9.8 and 37.1% in men and 10.1, 8.1, 2.6 and 28.0% in women, respectively. More than 50% of hypertensives and diabetics were on drug treatment, while only 20% of subjects reporting hyperlipidaemia were on medication. CONCLUSIONS: The results suggest the usefulness of self-administered electronic questionnaires for acquiring quick, low-cost and high response rate information in epidemiological surveys.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Femenino , Conductas Relacionadas con la Salud , Humanos , Internet , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
Human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS) and rare lymphoproliferative disorders in immunosuppressed patients. The risk of HHV-8 transmission by liver transplantation and the clinical manifestations of primary infection in this setting have yet to be determined. In order to evaluate this risk, we measured the seroprevalence of HHV-8 among 122 liver donors and their respective recipients before and after transplantation. Molecular methods and immunohistochemical analyses were performed to study the features of HHV-8 infection. Antibodies to HHV-8 were detected in sera of 4 donors before transplantation (3.3%) and of 3 recipients (2.4%). None of the 3 recipients, who were HHV-8 seropositive before transplantation, developed a KS during the follow-up. Four primary HHV-8 infections were detected among the 4 HHV-8 seronegative recipients who received a liver from an HHV-8 positive donor. Among these 4 recipients, 2 particularly immunosuppressed patients developed symptomatic diseases and died a few months after transplantation, harboring disseminated KS and HHV-8 positive lymphoproliferation. In these 2 patients, HHV-8 DNA genome sequences were detectable in peripheral blood mononuclear cells and other tissues with high viremia levels before and at the beginning of HHV-8-related diseases. In conclusion, in liver transplantation recipients, HHV-8 primary infection can be associated with fatal outcome. This study raises the question of screening liver donors for HHV-8--even in low HHV-8 infection prevalence countries--not systematically to exclude the graft but to monitor, clinically and biologically, patients who received a graft from an HHV-8-infected donor.