Post-transplant lymphoproliferative disease in liver transplant recipients.

INTRODUCTION: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. METHODS: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. RESULTS: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. CONCLUSION: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.

Differential Antitumoral Properties and Renal-Associated Tissue Damage Induced by Tacrolimus and Mammalian Target of Rapamycin Inhibitors in Hepatocarcinoma: In Vitro and In Vivo Studies.

Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.

Síndrome linfoproliferativo en el trasplante hepático / Post-transplant lymphoproliferative disease in liver transplant recipients

Introducción: el síndrome linfoproliferativo postrasplante (SLPT) es una complicación infrecuente que ensombrece el pronóstico de los pacientes sometidos a un trasplante hepático (TH). Su patogenia es multifactorial, siendo sus dos principales factores de riesgo la inmunodepresión y la infección del virus de Epstein- Barr (VEB); sin embargo, en actualidad se piensa que puede estar relacionada con otros factores. Métodos: estudio observacional en el que hemos analizado de forma retrospectiva 851 casos que fueron sometidos a un trasplante hepático, de los cuales diez casos han desarrollado un SLPT. Se han analizado sus características clinicopatológicas y el tratamiento recibido. Resultados: la incidencia del SLPT ha sido del 1,2% (10/851) y el tiempo medio de presentación desde el TH hasta el diagnóstico, de 36 meses (rango 1,2-144 meses). El lugar de presentación ha sido extranodal en todos los casos, siendo más frecuente la localización intestinal. Siete casos presentaron un SLPT monomorfo, todos ellos linfomas diferenciados de células B. El 50% de la serie presentó seronegatividad para el virus de Epstein-Barr. La supervivencia global ha sido del 50%. Entre estos pacientes, hemos observado tres casos de curación completa, un caso de estabilización de la enfermedad y otro caso de recurrencia. Conclusión: el SLPT es una complicación infrecuente que supone una amenaza para la vida del paciente. Para poder instaurar un diagnóstico precoz y un tratamiento que pueda modificar el curso de la enfermedad, es fundamental la identificación de los pacientes en riesgo (AU)

Introduction: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease (AU)