RESUMEN
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity. AIMS: To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients. METHODS: Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG. RESULTS: A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20-91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496). CONCLUSION: Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH.
Asunto(s)
Hepatitis Autoinmune/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Enfermedad Crónica , Femenino , Humanos , Inmunoglobulina G/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
INTRODUCTION: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood. PATIENTS AND METHODS: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT. RESULTS: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported. CONCLUSION: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.
Asunto(s)
Trasplante de Hígado , Adulto , Rechazo de Injerto/epidemiología , Antígenos HLA , Humanos , Isoanticuerpos , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Los fármacos inhibidores de la mTOR, everolimus (EVL) y sirolimus, son inmunosupresores con muy poco efecto nefrotóxico, limitado al desarrollo de proteinuria en algunos casos. En la prevención del rechazo agudo EVL combinado con tacrolimus a dosis reducidas tiene una eficacia y seguridad comparables a la inmunosupresión estándar con tacrolimus. La aplicación temprana de una inmunosupresión basada en EVL con minimización de la exposición al inmunosupresor calcineurínico en trasplantados hepáticos permite mejorar los resultados de la función renal, con tasas similares de eficacia y seguridad, tanto en el período de novo como de mantenimiento. En pacientes con disfunción renal establecida la introducción de EVL permite minimizar la exposición al inmunosupresor calcineurínico, con la consiguiente mejoría en la función renal. Aunque no hay evidencia suficiente para recomendar su uso para prevenir la recurrencia del hepatocarcinoma y la progresión de tumores de novo, es práctica clínica habitual utilizarlos en este contexto (AU)
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice (AU)
Asunto(s)
Humanos , Trasplante de Hígado/métodos , Everolimus/uso terapéutico , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Insuficiencia Renal/complicaciones , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/inmunología , Estudios ProspectivosRESUMEN
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice.
Asunto(s)
Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Everolimus/efectos adversos , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Guías de Práctica Clínica como AsuntoAsunto(s)
Quelantes/efectos adversos , Degeneración Hepatolenticular/complicaciones , Penicilamina/efectos adversos , Seudoxantoma Elástico/inducido químicamente , Seudoxantoma Elástico/complicaciones , Adulto , Quelantes/uso terapéutico , Femenino , Degeneración Hepatolenticular/tratamiento farmacológico , Humanos , Penicilamina/uso terapéuticoRESUMEN
No disponible
Asunto(s)
Humanos , Femenino , Adulto , Degeneración Hepatolenticular/complicaciones , Seudoxantoma Elástico/inducido químicamente , Encefalina D-Penicilamina (2,5)/efectos adversos , Acetato de Zinc/uso terapéuticoRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Adulto , Trasplante de Hígado , Mucormicosis/complicaciones , Dermatomicosis/diagnóstico , Infección de la Herida Quirúrgica/cirugía , Desbridamiento , Mucorales/patogenicidad , Profilaxis Antibiótica , Antifúngicos/uso terapéuticoAsunto(s)
Dermatomicosis/etiología , Trasplante de Hígado , Mucormicosis/etiología , Infecciones Oportunistas/etiología , Complicaciones Posoperatorias/etiología , Pared Abdominal/microbiología , Pared Abdominal/cirugía , Lesión Renal Aguda/etiología , Adulto , Anfotericina B/uso terapéutico , Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Infecciones por Clostridium/etiología , Infecciones por Citomegalovirus/etiología , Desbridamiento , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/cirugía , Hepatitis/cirugía , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Mucormicosis/tratamiento farmacológico , Mucormicosis/cirugía , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/cirugía , Complicaciones Posoperatorias/microbiología , Disfunción Primaria del Injerto/cirugía , Reoperación , Triazoles/uso terapéuticoRESUMEN
A 56-year-old man attended the emergency room with respiratory failure, deteriorated general status, fatigue, and diarrhea. His clinical history included a liver transplant because of alcoholic cirrhosis, which developed to hepatocellular carcinoma. Initial immunosuppression consisted of corticosteroids, tacrolimus, and mycophenolate mofetil. Examination of the explant revealed vascular invasion, and tacrolimus was replaced with everolimus. The patient presented recurrence of the carcinoma with peritoneal implants, and treatment with sorafenib was started. He was admitted to the gastroenterology department and, after withdrawal of sorafenib, the patient improved clinically. However, 6 days later, he was admitted to the intensive care unit with acute respiratory failure and metabolic acidosis. The final diagnosis was cardiogenic shock. Although cardiogenic shock is not mentioned in the summaries of product characteristics of sorafenib or everolimus, there are reports of a relationship between cardiotoxicity and antiangiogenic therapy that inhibits the proliferation of vascular smooth muscle cells, as is the case with these drugs. We believe that there is a relationship between sorafenib (especially when combined with everolimus) and cardiogenic shock. Application of the Karch and Lasagna algorithm to assess the causality of the reaction induced by the combination of sorafenib and everolimus revealed the relationship to be probable.
Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Niacinamida/análogos & derivados , Compuestos de Fenilurea/efectos adversos , Choque Cardiogénico/inducido químicamente , Sirolimus/análogos & derivados , Everolimus , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Sirolimus/efectos adversos , SorafenibRESUMEN
We report a case of a 55-year-old male with chronic hepatitis C virus infection and compensated liver disease treated with sorafenib for advanced hepatocarcinoma (Barcelona Clinic Liver Cancer stage C). At follow-up, the patient developed hypertension, which was well controlled with beta-blocker medication, and an aortic dilation detected by abdominal computerized tomography and echocardiography. There are some reports of the side effects of sorafenib on the cardiovascular system. The patient had no cardiac or aortic pathology before the start of this palliative chemotherapy. There is an article that describes the development of an aortic aneurysm in a patient with uncontrolled hypertension, who received treatment with sorafenib for renal carcinoma. However, our patient had a good control of blood pressure. The adverse vascular effects of Sorafenib may be due to the inhibition of the proliferation of vascular endothelial muscle cells. We believe that this case illustrates a probable relationship between sorafenib and aortic dilatation according to the Karch and Lasagna causality algorithm.