RESUMEN
Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.
Asunto(s)
Supervivencia de Injerto , Hepatitis C/prevención & control , Trasplante de Pulmón/métodos , Donantes de Tejidos , Obtención de Tejidos y Órganos , Receptores de Trasplantes , Adulto , Hepacivirus/fisiología , Hepatitis C/transmisión , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.
Asunto(s)
Enfermedades Autoinmunes/cirugía , Familia , Rechazo de Injerto/etiología , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Donadores Vivos , Complicaciones Posoperatorias/etiología , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Factores de RiesgoRESUMEN
The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, intrapulmonary vascular dilatation, and abnormal gas exchange, and is found in 10-32% of patients with liver disease. Liver transplantation is the only known cure for HPS, but patients can develop severe posttransplant hypoxemia, defined as a need for 100% inspired oxygen to maintain a saturation of ≥85%. This complication is seen in 6-21% of patients and carries a 45% mortality. Its management requires the application of specific strategies targeting the underlying physiologic abnormalities in HPS, but awareness of these strategies and knowledge on their optimal use is limited. We reviewed existing literature to identify strategies that can be used for this complication, and developed a clinical management algorithm based on best evidence and expert opinion. Evidence was limited to case reports and case series, and we determined which treatments to include in the algorithm and their recommended sequence based on their relative likelihood of success, invasiveness, and risk. Recommended therapies include: Trendelenburg positioning, inhaled epoprostenol or nitric oxide, methylene blue, embolization of abnormal pulmonary vessels, and extracorporeal life support. Availability and use of this pragmatic algorithm may improve management of this complication, and will benefit from prospective validation.
Asunto(s)
Algoritmos , Síndrome Hepatopulmonar/cirugía , Hipoxia/terapia , Trasplante de Hígado/efectos adversos , Terapia Combinada , HumanosRESUMEN
A microemulsion formulation of cyclosporine (CsA) has improved absorption compared with the original form. The purpose of this case control study was to assess the safety and efficacy of the microemulsion without intravenous CsA for induction immunosuppression in adult liver transplantation. Twenty-one consecutive patients receiving induction immunosuppression with the microemulsion 15 mg/kg/day were compared with 20 patients receiving intravenous CsA and the original oral form. Both groups received the same dose of methylprednisilone. Twenty of 21 patients receiving the microemulsion required no intravenous CsA to achieve target CsA levels. All patients receiving the original form received initial intravenous CsA. There was no difference in trough CsA levels between the two groups at 24 and 48 hours. The microemulsion group had 24 hr and 48 hr trough CsA levels of 227+/-15 and 520+/-300 ng/ml by monoclonal RIA while the intravenous CsA group had 24 and 48 hr trough levels of 293+/-18 and 405+/-91 ng/ml. CsA levels analyzed by HPLC were 20% lower than by RIA. The frequency of adverse events resulting in reduction of drug dosage was similar for the microemulsion and the original form: neurotoxicity (23 vs. 40%, P=.30); nephrotoxicity (25 vs. 45%, P=.32), and no patients required dialysis. There was no difference in septic complications. One patient required discontinuation of the microemulsion in an attempt to reverse severe neurotoxicity. A total of 75% of microemulsion patients were rejection free at 3 months while only 35% of CsA patients remained rejection free (P=0.02). These data suggest that the use of the microemulsion without intravenous CsA in liver transplantation is safe and efficacious, and may result in decreased episodes of acute rejection.
Asunto(s)
Ciclosporina/administración & dosificación , Trasplante de Hígado/inmunología , Adulto , Ciclosporina/farmacocinética , Relación Dosis-Respuesta a Droga , Emulsiones/efectos adversos , Emulsiones/toxicidad , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Absorción Intestinal , Trasplante de Hígado/mortalidad , Enfermedades del Sistema Nervioso/inducido químicamente , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Liver transplantation for hepatitis B virus (HBV) has been associated with a high rate of reinfection and graft failure. Lamivudine, a potent inhibitor of HBV replication, has been shown to prevent viral recurrence after transplantation. METHODS: The effectiveness of lamivudine monotherapy for the management of HBV recurrence after liver transplantation was assessed. Lamivudine was used in three patient groups: (1) patients started before transplantation and continued after transplantation (n = 13); (2) patients treated after transplantation (n = 15); and (3) patients with de novo hepatitis B after transplantation (n = 4). RESULTS: Median follow-up on lamivudine was 24 months. Active viral replication (HBV-DNA+) was seen in 17 (53%) of 32 at treatment initiation. All lost HBV-DNA at a mean of 2.4+/-1.6 months after lamivudine initiation. Twenty-six (81%) patients remain free of viral recurrence. Six (19%) patients have evidence of breakthrough infection with the YMDD mutant of HBV, two of whom progressed to graft failure. All four patients in group 1 who developed breakthrough had evidence of hepatitis B surface antigen expression in the explanted liver by immunohistochemistry despite being serum HBV-DNA negative before transplantation. No difference was observed among the three groups in DNA clearance or breakthrough rates. CONCLUSIONS: Lamivudine achieves viral DNA clearance in almost all patients. Expression of viral antigens in the liver seems to identify patients at risk of developing HBV-DNA recurrence. Disease-free survival of 81% at 22 months is similar to data with hepatitis B immunoglobulin therapy. Given the safe clinical profile and high efficacy in the prevention of disease recurrence, lamivudine will favorably change the outlook of liver transplantation for HBV.
Asunto(s)
Hepatitis B/tratamiento farmacológico , Lamivudine/uso terapéutico , Trasplante de Hígado , Complicaciones Posoperatorias , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Anciano , ADN Viral/análisis , ADN Viral/genética , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Hígado/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Cuidados Preoperatorios , Recurrencia , Replicación Viral/efectos de los fármacosRESUMEN
Our understanding of cyclosporine (CsA) administration for liver transplantation has significantly improved over the past decade. Cyclosporine is a highly lipophilic molecule, and the original galenic formulation, Sandimmune, was highly dependent on bile flow and gut motility for its absorption. Sandimmune's poor absorption profile produced erratic CsA levels after liver transplantation. A new microemulsification formulation of CsA, Neoral (CsA-ME), was developed to overcome these limitations. The NOF-1 study confirmed the superiority of CsA-ME's absorption compared with Sandimmune; CsA-ME had a more consistent and reliable absorption, with lower intrapatient variability and improved dose linearity with drug exposure as measured by area under the concentration-time curve (AUC). These advantages translated into more reliable CsA predose concentrations and less toxicity. An analysis of the pharmacokinetic data showed that 2-hour postdose CsA levels (C2) provided a better measure of immune suppression than did trough levels (C0). The LIS2T study recently confirmed and extended these data by showing equivalent efficacy between CsA-ME using C2 monitoring or tacrolimus in liver transplant patients, with a similar incidence of adverse events except for a higher rate of diabetes mellitus and diarrhea with tacrolimus. These data confirmed that the improved CsA-ME formulation, when used in conjunction with optimized drug-monitoring protocols, is well tolerated after transplantation and provides low rates of graft rejection.
Asunto(s)
Ciclosporina/uso terapéutico , Trasplante de Hígado/inmunología , Administración Oral , Ciclosporina/administración & dosificación , Ciclosporina/farmacocinética , Relación Dosis-Respuesta a Droga , Emulsiones , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Absorción Intestinal , Resultado del TratamientoRESUMEN
BACKGROUND: Obesity is thought to be associated with higher rates of morbidity and mortality after liver transplantation (LT); however, its actual impact is difficult to evaluate, in part because of the confounding effects of fluid accumulation on body mass index (BMI). OBJECTIVE: We sought to define the effects of conventional BMI (cBMI) and modified BMI (mBMI; calculated by multiplying the BMI by serum albumin level to compensate for fluid accumulation), on the outcome of LT recipients overall. METHODS: A cohort of 507 patients who underwent LT from April 2000 to August 2006 were analyzed. RESULTS: Pre-LT diabetes mellitus was seen somewhat more frequently in the higher mBMI group (P = .054), whereas there was no difference across cBMI categories. The recipients at extremes of cBMI (>40 kg/m(2) and <18.5 kg/m(2)) had significantly lower patient and graft survival than other groups (P = .038 and P = .010, respectively); however, no statistically significant differences were found in overall patient and graft survival across mBMI categories. There were no differences in duration of intensive care unit stay, duration of overall hospital stay, and vascular complications after LT among mBMI categories. CONCLUSIONS: Pre-LT obesity alone, when estimated by mBMI rather than by cBMI, should not be a contraindication for LT.
Asunto(s)
Índice de Masa Corporal , Trasplante de Hígado , Obesidad/diagnóstico , Adulto , Biomarcadores/sangre , Contraindicaciones , Femenino , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/sangre , Obesidad/complicaciones , Obesidad/mortalidad , Ontario , Selección de Paciente , Complicaciones Posoperatorias/mortalidad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Albúmina Sérica/análisis , Albúmina Sérica Humana , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Trasplante de Hígado/fisiología , Complicaciones Posoperatorias/epidemiología , Análisis Actuarial , Adulto , Carcinoma Hepatocelular/cirugía , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Hepatopatías/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/inmunología , Trasplante de Hígado/mortalidad , Complicaciones Posoperatorias/clasificación , Recurrencia , Estudios Retrospectivos , Sepsis/epidemiología , Tasa de Supervivencia , Factores de TiempoAsunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Hepatitis C/cirugía , Trasplante de Hígado , Ribavirina/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C/prevención & control , Humanos , Pruebas de Función Hepática , Complicaciones Posoperatorias , ARN Viral/sangre , Recurrencia , Factores de TiempoAsunto(s)
Ciclosporina/administración & dosificación , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Hígado/inmunología , Administración Oral , Estudios de Casos y Controles , Ciclosporina/uso terapéutico , Emulsiones , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Inyecciones Intravenosas , Factores de TiempoRESUMEN
Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor =age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.
Asunto(s)
Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Donadores Vivos , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Algoritmos , Colestasis , Funcionamiento Retardado del Injerto , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow-up was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts >/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are currently free of any biliary complications. D-D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.
Asunto(s)
Enfermedades de las Vías Biliares/cirugía , Trasplante de Hígado/efectos adversos , Donadores Vivos , Adulto , Factores de Edad , Anciano , Anastomosis Quirúrgica , Conductos Biliares/anomalías , Conductos Biliares/cirugía , Procedimientos Quirúrgicos del Sistema Biliar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Tiempo de Internación , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end-stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty-four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end-stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1-year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT.
Asunto(s)
Hepatectomía/métodos , Trasplante de Hígado/fisiología , Donadores Vivos/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Recolección de Tejidos y Órganos/métodos , Listas de Espera , Adulto , Cadáver , Humanos , Trasplante de Hígado/mortalidad , Selección de Paciente , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a second messenger that releases Ca2+ from hepatocyte microsomes. The toxic alkaloid ryanodine modulates Ca2+ release via a receptor (RyR) identified in a variety of cell systems, but its regulation and functional significance in liver are undefined. Similarly, the role in hepatocyte Ca2+ regulation of adenosine 5'-cyclic diphosphate-ribose (cADPR), which is the putative endogenous ligand for RyR in other cell systems, has not been defined. Utilizing microsomes and permeabilized cells, we have investigated Ca2+ regulation in hepatocytes and, in particular, effects of ryanodine, cADPR, and other putative modulators on Ca2+ release and compared these with Ins(1,4,5)P3-induced Ca2+ release. Ryanodine at > or = 50 microM released 20% of microsomal Ca2+, and, in contrast to Ins(1,4,5)P3, no potentiation was observed with guanosine 5'-triphosphate and polyethylene glycol. Ins(1,4,5)P3-induced Ca2+ release was demonstrable after maximal ryanodine-induced Ca2+ release, suggesting that distinct Ca2+ stores are involved. cADPR (5 microM) did not induce Ca2+ release, alone or in combination with calmodulin or hepatic cytosol, nor did it influence ryanodine-induced release, in microsomes or permeabilized hepatocytes (in which ryanodine released 25% of the sequestered Ca2+). Ryanodine-induced Ca2+ release in microsomes was not influenced by 20 mM caffeine, which itself did not mobilize Ca2+, but was prevented by 500 microM tetracaine, which was shown to induce Ca2+ release. We conclude that ryanodine is capable of mobilizing Ca2+ in the hepatocyte from microsomal stores that are distinct from those that can be regulated by Ins(1,4,5)P3 but that cADPR has no such effect. These data suggest that cADPR does not serve as the endogenous ligand for RyR in liver cells or that the site of action of ryanodine in hepatocyte microsomes is distinct from that in other cell types.
Asunto(s)
Calcio/metabolismo , Hígado/metabolismo , Microsomas Hepáticos/metabolismo , Rianodina/farmacología , Adenosina Difosfato Ribosa/análogos & derivados , Adenosina Difosfato Ribosa/farmacología , Adenosina Trifosfato/metabolismo , Animales , Cafeína/farmacología , Permeabilidad de la Membrana Celular , Células Cultivadas , ADP-Ribosa Cíclica , Guanosina Trifosfato/farmacología , Inositol 1,4,5-Trifosfato/farmacología , Ionomicina/farmacología , Cinética , Hígado/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tetracaína/farmacología , Factores de TiempoRESUMEN
Prevention of graft rejection while minimizing morbidity remains the single most important objective in liver transplantation. Advances in immunosuppression have provided excellent patient and graft survival with relatively low incidences of acute rejection. However, it is apparent that the toxicity of the present immunosuppressive drugs accounts for much of the morbidity after transplantation. Attention is now being focused on combination drug therapies to reduce morbidity while maintaining the excellent results achieved with present immunosuppressive agents.
Asunto(s)
Refuerzo Inmunológico de Injertos/métodos , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Adulto , Niño , Humanos , Inmunosupresores/efectos adversos , Morbilidad , PronósticoRESUMEN
The University of Toronto Liver Transplant Program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers that impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Significant advances over the past decade and a half in immunosuppressive drugs and monitoring, patient selection, and infectious management have contributed to markedly improved patient and graft survival rates. Nevertheless, we continue to face 2 major challenges: a growing scarcity of donor organs, a problem partially addressed through development of living-related liver donation, and recurrent viral hepatitis. We expect to remain on the forefront of ongoing research to provide solutions to these and other barriers to the full deployment of liver transplantation in the year 2000.
Asunto(s)
Trasplante de Hígado , Adulto , Niño , Supervivencia de Injerto , Hepatitis B/cirugía , Hepatitis C/cirugía , Hospitales Pediátricos , Humanos , Terapia de Inmunosupresión , Control de Infecciones/métodos , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Donadores Vivos/estadística & datos numéricos , Ontario/epidemiología , Selección de Paciente , Tasa de SupervivenciaRESUMEN
The University of Toronto liver transplant program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers which impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Our group has had a special interest in transplantation for viral hepatitis. We demonstrated the role of HBV DNA as a prospective factor in both viral recurrence and survival. We further studied a number of agents to prevent re-infection including PGE, HBIG and more recently lamivudine. Although the short-term results of transplantation for HCV appear excellent, reinfection of the graft and development of chronic hepatitis and cirrhosis may make long-term results problematic. Therefore, we have directed attention to studies of pathogenesis and treatment of HCV in liver transplantation. Our studies have demonstrated a unique role for ribavirin as an immunomodulatory agent which can benefit the course of posttransplant HCV. Future studies will examine combination therapy in an attempt to eradicate the virus. Our group also has been interested in PNF and FHF and have demonstrated a positive effect of PGE in this setting. As we look to the future, the greatest challenges facing transplantation are the shortage of organ donors and the toxic effects of long-term immunosuppression. Our group now has established research efforts both in tolerance induction and xenotransplantation which we feel are necessary to make transplantation an effective, universal treatment for end stage organ failure.
Asunto(s)
Trasplante de Hígado/estadística & datos numéricos , Adulto , Alprostadil/uso terapéutico , Antivirales/uso terapéutico , Niño , Supervivencia de Injerto , Hepatitis B/prevención & control , Hepatitis B/cirugía , Hepatitis C/cirugía , Hospitales Universitarios , Humanos , Inmunización Pasiva , Inmunoglobulinas , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Lamivudine/uso terapéutico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/inmunología , Trasplante de Hígado/mortalidad , Ontario , Selección de Paciente , Recurrencia , Estudios Retrospectivos , Ribavirina/uso terapéutico , Tasa de Supervivencia , Trasplante HeterólogoRESUMEN
Neoral, a microemulsion formulation of cyclosporin A (CsA), has improved absorption compared to Sandimmune and has allowed induction of immunosuppression in liver transplantation (LT) without the use of intravenous (i.v.) CsA. The improved bioavailability with less inter- and intra-patient dosing variability coupled with the lack of requirement for i.v. CsA may provide a mechanism for cost savings when Neoral is used for induction immunosuppression. This retrospective case-control study compares the relative costs associated with Neoral induction without i.v. CsA versus induction with i.v. CsA followed by oral CsA in adult liver transplant recipients. Twenty consecutive patients receiving Neoral 12-15 mg/kg per d were compared to a control group of 21 patients receiving i.v. CsA followed by oral CsA for induction. Both groups received the same rapidly tapered dose of methyl-prednisilone. Health care resource utilization was assigned based on days in hospital and acute rejection episodes (ARE). Hospital per diem rates at specified care levels were used to assign costs associated with hospital stay, while a previously developed case-costing model was used to assign costs to episodes of acute rejection. All patients were followed for a 3-month period post-transplant. Although there was a trend towards shorter hospital stay in the Neoral group the majority of cost savings were achieved by reducing costs associated with episodes of acute rejection. There were seven and 19 episodes of ARE in the Neoral and i.v. CsA groups respectively (p < 0.05.) A separate cost effective assessment of the effect of reducing rejection by decision tree analysis demonstrated a cost reduction of $2162 per patient. The savings achieved with Neoral proved robust on sensitivity analysis. The change of practice to an induction immunosuppression regimen of Neoral without i.v. CsA has achieved a cost savings in adult liver transplantation at our center.
Asunto(s)
Ciclosporina/economía , Trasplante de Hígado/economía , Adulto , Canadá , Estudios de Casos y Controles , Ahorro de Costo , Ciclosporina/administración & dosificación , Costos de los Medicamentos , Emulsiones , Rechazo de Injerto , Costos de Hospital , Humanos , Infusiones Intravenosas , Tiempo de Internación , Estudios RetrospectivosRESUMEN
Familial amyloid polyneuropathy is an autosomal dominant disorder in which the liver produces a variant prealbumin that is deposited along nerves, leading to a progressive and fatal polyneuropathy that begins in the third decade of life. Liver transplantation has been the only successful treatment to date. Apart from the production of the variant protein, there are no other abnormalities in these amyloid livers. We describe two cases in which, at the time of transplantation, the amyloid livers were subsequently used for transplantation in another patient, and we discuss the implications.