RESUMEN
Donor's CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period. METHODS: The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy. RESULTS: The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A-status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P < 0.0001). Acute rejection episodes (3.6 vs 23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P > 0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mL-1 (20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated with high tacrolimus concentrations (>20 ng mL-1 ) in the first week after transplantation (13/27 of control and 2/9 of CYPtest patients). CONCLUSION: CYP3A-status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).
Asunto(s)
Trasplante de Hígado , Tacrolimus , Citocromo P-450 CYP3A/genética , Genotipo , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Tacrolimus/efectos adversos , Receptores de TrasplantesRESUMEN
INTRODUCTION: In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. AIM: The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. METHOD: Retrospective data analysis was performed after primary liver transplantations (n = 319). RESULTS: impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). CONCLUSIONS: Selection of personalized immunosuppressive medication has a positive effect on renal function.
Asunto(s)
Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Inmunosupresores/efectos adversos , Riñón/fisiopatología , Cirrosis Hepática/cirugía , Trasplante de Hígado/efectos adversos , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Constricción , Diabetes Mellitus/etiología , Diabetes Mellitus/fisiopatología , Femenino , Síndrome Hepatorrenal/complicaciones , Humanos , Inmunosupresores/administración & dosificación , Riñón/irrigación sanguínea , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Medicina de Precisión , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Vena Cava InferiorRESUMEN
Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer's presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers.
Asunto(s)
Costos de los Medicamentos , Sustitución de Medicamentos , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/economía , Inmunosupresores/administración & dosificación , Inmunosupresores/economía , Trasplante de Órganos , Análisis Costo-Beneficio , Ciclosporina/administración & dosificación , Ciclosporina/economía , Preparaciones de Acción Retardada , Interacciones Farmacológicas , Monitoreo de Drogas , Sustitución de Medicamentos/efectos adversos , Sustitución de Medicamentos/economía , Medicamentos Genéricos/administración & dosificación , Humanos , Hungría , Inmunosupresores/efectos adversos , Trasplante de Riñón , Tacrolimus/administración & dosificación , Tacrolimus/economía , Equivalencia TerapéuticaRESUMEN
About 6500-7000 people/year die in Hungary due to liver cirrhosis which is often complicated with hepatic encephalopathy (HE). While conventional interpretation is that hepatic encephalopathy is a consequence of high blood ammonia level, recent data indicate that the degree of encephalopathy is related to systemic inflammatory response during decompensation. In this review the authors overview and analyze the latest treatment modalities of hepatic encephalopathy based on most recent findings. They found that frequently used evidence based treatment which apply metronidazole, neomycine or disaccharides was only partially effective in clinical studies. Use of rifaximine only is supported by grade I evidence, however it is quite a costly drug. The authors could not identify a generally accepted guideline for the treatment of HE with a systematic literature review, although it has significant effect on survival after liver transplantation. Therefore, the authors urge to develop a consensus guideline for the treatment of HE.
Asunto(s)
Amoníaco/metabolismo , Antiinfecciosos/uso terapéutico , Enfermedad Hepática en Estado Terminal/tratamiento farmacológico , Enfermedad Hepática en Estado Terminal/cirugía , Fármacos Gastrointestinales/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/cirugía , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Amoníaco/antagonistas & inhibidores , Amoníaco/sangre , Colon/microbiología , Dipéptidos/uso terapéutico , Disacáridos/uso terapéutico , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/metabolismo , Enfermedad Hepática en Estado Terminal/microbiología , Enfermedad Hepática en Estado Terminal/mortalidad , Medicina Basada en la Evidencia , Encefalopatía Hepática/etiología , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/microbiología , Encefalopatía Hepática/mortalidad , Humanos , Hungría/epidemiología , Concentración de Iones de Hidrógeno , Lactobacillus/efectos de los fármacos , Lactobacillus/crecimiento & desarrollo , Lactulosa/uso terapéutico , Laxativos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Cirrosis Hepática/mortalidad , Metronidazol/uso terapéutico , Neomicina/uso terapéutico , Rifamicinas/uso terapéutico , Rifaximina , Índice de Severidad de la Enfermedad , Alcoholes del Azúcar/uso terapéutico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: The transjugular intrahepatic portosystemic shunt (TIPS) is widely used for the treatment of portal hypertension in adults, but no studies have defined the best approach to treat portal hypertension in pediatric patients. Pediatric use of TIPS is rare even in large centers of adult practice. The migration of stents has also been reported as a complication in adults. There is no standard way to treat this type of complication, and it is not always clear whether immediate removal or watchful waiting is safer for the patient. CASE REPORT: We report the case of an 11-year-old patient who underwent urgent TIPS implantation due to variceal bleeding, after unsuccessful sclerotherapy. During the procedure, due to the deep impact of the stent, a second, telescopic, stent was inserted. The portal pressure decreased, no further bleeding occurred, and the patient was listed for transplantation. Three weeks later a routine chest X-ray discovered the migration of the second stent into the right ventricle. No interventional radiological removal or open heart surgery was available for the transplant waiting list patient. The patient underwent uneventful combined liver-kidney transplantation. During the 6-year follow-up period the child had no signs of hemodynamic instability, and his somatic and mental development were appropriate. CONCLUSIONS: To our knowledge this case is the first publication on a heart-impacted TIPS stent in a child. The watchful waiting was justified by uneventful combined liver-kidney transplantation and long-term follow-up. This case also underlines the need for best practice guidelines in pediatric portal hypertension.
Asunto(s)
Ventrículos Cardíacos , Derivación Portosistémica Intrahepática Transyugular/instrumentación , Falla de Prótesis , Stents , Niño , Estudios de Seguimiento , Humanos , Trasplante de Riñón , Trasplante de Hígado , Masculino , Espera VigilanteRESUMEN
The authors report on their experiences related to the first adult live donor liver transplantation performed in Hungary. The transplantation was done between brother and sister on 19th of November, 2007. The right lobe of the 33-year-old healthy male's donor liver (segments 5-8) was removed and implanted into the 23-year-old female suffering from cirrhosis on the ground of autoimmune hepatitis. The implantation of the right liver lobe was done after own hepatectomy in orthotopic position. Liver function has improved rapidly following the transplantation. The donor was discharged on the 10th post-operative day with stable liver function. He had full rehabilitation, got back to work, and control check-ups showed a significant liver regeneration. Two years after transplantation, the recipient also lives an active life with compensated liver function and she is under regular medical check-up. With the case report, authors overview the indications and techniques of living donor right-lobe liver transplantation.
Asunto(s)
Hepatitis Autoinmune/cirugía , Trasplante de Hígado/métodos , Hígado/fisiopatología , Hígado/cirugía , Donadores Vivos , Recolección de Tejidos y Órganos/métodos , Adulto , Femenino , Hepatectomía/métodos , Hepatectomía/rehabilitación , Humanos , Hungría , Hígado/diagnóstico por imagen , Hígado/patología , Pruebas de Función Hepática , Regeneración Hepática , Masculino , Hermanos , Recolección de Tejidos y Órganos/rehabilitación , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The role of covered stent in the management of biliary complications is not yet defined in liver transplant recipients. This Case Report presents a patient with anastomotic stricture and leakage with biloma treated with a covered stent 32 months following liver transplantation. Signs of in-stent restenosis developed 52 months following covered stent placement, which was resolved by balloon dilation. There were no complications during the interventions. The latest follow-up, at 69 months following primary and 19 months following secondary percutaneous intervention, shows a patent covered stent without any clinical or morphological sign of further restenosis. The clinical success with long-term follow-up data suggests that covered stent implantation can be a rational, minimally invasive option for simultaneous treatment of bile duct stenosis and bile leak following liver transplantation in selected cases.
Asunto(s)
Colestasis/etiología , Colestasis/terapia , Fallo Hepático/cirugía , Trasplante de Hígado/efectos adversos , Stents , Adulto , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestasis/diagnóstico por imagen , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Fallo Hepático/patología , Fallo Hepático/virología , Trasplante de Hígado/métodos , Medición de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: Availability of suitable donor organs has always limited liver transplantations. Use of marginal donors (Extended Donor Criteria) for liver transplantation is an alternative to overcome the organ shortage. The aim of this study was to analyze the characteristics of organ donation in Hungary with special regard to marginal donors. METHODS: We reviewed data from donors and recipients between January 2003 and December 2008 retrospectively. Extended donor criteria were adopted from international recommendations. RESULTS: During this period, 1078 donors were reported to the clinic. 835 (77.4%) donors were excluded from liver transplantation and 243 (22.6%) were implanted. From the 243 transplantations 40 recipients (16%) received marginal graft, 203 (84%) received non-marginal graft. Extended Donor Criteria status had no negative impact on the patient and graft survival, postoperative graft dysfunction, and other complications. Recurrence of Hepatitis C occurred earlier in those patients who received marginal graft. CONCLUSION: There is an increasing number of patients waiting for liver transplantation in Hungary. There is no significant difference in morbidity and mortality of patients receiving marginal or non-marginal graft. Use of marginal grafts should be avoided in Hepatitis C virus positive recipients. Acceptance of older donors for liver transplantation should be considered.
Asunto(s)
Selección de Donante/normas , Pruebas de Función Hepática , Trasplante de Hígado , Donantes de Tejidos , Obtención de Tejidos y Órganos/normas , Factores de Edad , Índice de Masa Corporal , Supervivencia de Injerto , Hepatitis C/diagnóstico , Humanos , Hungría , Hipernatremia/complicaciones , Hipotensión/complicaciones , Unidades de Cuidados Intensivos , Isquemia/complicaciones , Tiempo de Internación , Recurrencia , Análisis de Supervivencia , Donantes de Tejidos/provisión & distribuciónRESUMEN
UNLABELLED: Liver transplantation is a routinely used therapeutic choice in the treatment of end stage liver disease. Portal vein stenosis is a rare vascular complication after liver transplantation. We report the interventional radiological management of three cases of portal vein stenosis. AIM: The surgical management of portal vein stenosis can be hazardous for the patient and the transplanted liver in the early post-transplantation period. In general, interventional radiological methods are tolerable for patients and can be safely performed with high success rate. The aim of this report is to analyze the feasibility, the risks and the efficacy of the percutaneous transhepatic self expanding metallic stent placement into the portal vein. METHOD: Three of the 396 liver transplantations cases in Budapest developed significant portal vein stenosis. In these cases, ultrasound guided percutaneous transhepatic portal vein puncture with fine needle was performed. The tract was dilated with a coaxial dilator set, and an adequately sized sheath introducer was inserted into the liver parenchyma. Two nitinol and one stainless steel self expanding metallic stent were implanted at the stenotic portal vein anastomoses. The tract was embolized with gelfoam particles (1 case), or coils (1 case). In the third patient no tract embolization was performed. RESULT: All treatments were technically successful, without minor or major complications. In two cases the amount of free abdominal fluid decreased significantly, and in the third case the esophageal varicosity regressed. The morphological success was documented with ultrasound and computed tomography examination. Two patients are alive and well after 10 and 39 months of follow up, while the third patient died after one month in multi organ failure. CONCLUSION: Percutaneous transhepatic metallic stent placement for the treatment of post-transplantation portal vein stenosis is a safe and effective method.
Asunto(s)
Trasplante de Hígado/efectos adversos , Vena Porta/patología , Vena Porta/cirugía , Stents , Adulto , Anastomosis Quirúrgica , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Ultrasonografía Doppler de Pulso , Grado de Desobstrucción VascularRESUMEN
INTRODUCTION: The authors summarize the characteristics of biliary complications following liver transplantation in the Hungarian liver transplant program. Aims were to analyze the frequency and the types of biliary complications as well as their effect on the patient and graft survival. The authors observed the known risk factors in the Hungarian practice, and they also try to find unknown risk factors for biliary complications. They review the therapy of biliary complications. METHOD: In the retrospective study, patients were divided into two groups, with and without biliary complication after liver transplantation. These two groups were compared with many factors, and with the survivals. The biliary complication group was divided into two parts: those who had an early and those with a late biliary complication. These two new groups were also compared with the controls. The results are summarized in tables and statistical figures. Categorical variables are evaluated by chi 2 -test, continuous ones are with Levine Test (for homogenicity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis. RESULTS: Biliary complication appeared in 25% of the patients. The most frequent complications were stenosis (18%), biliary leakage (9%), biliary necrosis (6%), and ischaemic type of biliary lesions (3%). The 5-year survival is worse when biliary complications were diagnosed (55%) than without such a complication (66%). In the biliary complication group the retransplantation rate was higher (15%). The most frequent treatments were interventional radiologic methods (69%), surgical methods (17%), and the ERCP. CONCLUSIONS: The rate of biliary complications met the international reviews. Risk factors for biliary complications were cholangitis, hepatic artery thrombosis and stenosis, high rate of intraoperative blood transfusions, and acute rejection. Biliary complications frequently associated with the initial poor function of the transplanted graft. Early biliary complications have a negative impact on patient survival, while late complications influence a decreased quality of life. Biliary complications were treated mostly by interventional radiologic procedures.
Asunto(s)
Bilis , Enfermedades de las Vías Biliares/etiología , Sistema Biliar/patología , Trasplante de Hígado/efectos adversos , Adulto , Anciano , Atresia Biliar/etiología , Sistema Biliar/fisiopatología , Enfermedades de las Vías Biliares/diagnóstico por imagen , Enfermedades de las Vías Biliares/patología , Enfermedades de las Vías Biliares/fisiopatología , Colestasis/etiología , Constricción Patológica/etiología , Femenino , Humanos , Hungría , Isquemia/etiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Necrosis/etiología , Calidad de Vida , Radiografía Intervencional , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
The time course of free radical reactions is evaluated by the authors. Within pretransplant patients as of their poorly functioning metabolism free radical overproduction may be observed, hence their antioxidant capacity decreases. When the graft is functioning well, the free radical-antioxidant balance of homeostasis is reestablished. During the early postoperative period, when symptoms (acute rejection, infection, acute tubular necrosis, cholestasis) appear, free radical reactions increase. The authors demonstrate, this is strengthened by the fact that the mediator [interleukin-6 (IL-6), C-reactive protein, serum amyloid-A], and enzyme levels that take part in the free radical processes rise. The monitoring of these parameters during the early postoperative period is a good early indicator for acute rejection and for the effect of therapy. During acute rejection just as during infection most of these parameters increased significantly compared to the healthy control. They show the activation of the immune system but they are not useful for differential diagnosis, with the exception of IL-6 which we measured in larger quantities during bacterial infection but not so in acute rejection. For the prediction of early renal graft function we used urinary enzyme levels (dipeptidyl-aminopeptidase, glutathione-S-transferase). Tissue damage is followed by enzyme increasing and antioxidant capacity depletion. With choosing of adequate tests, the perioperative redox homeostasis of the transplanted patients can be monitored and with dosing the antioxidants the uncontrolled forming of reactive oxygen metabolites can also be decreased and checked.
Asunto(s)
Radicales Libres/metabolismo , Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Trasplante de Hígado , Oxidación-Reducción , Enfermedad Aguda , Adulto , Antioxidantes/administración & dosificación , Biomarcadores/sangre , Biomarcadores/orina , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/orina , Femenino , Glutatión Transferasa/orina , Rechazo de Injerto/sangre , Rechazo de Injerto/orina , Humanos , Interleucina-6/sangre , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Neopterin/sangre , Proteína Amiloide A Sérica/metabolismoRESUMEN
UNLABELLED: What is already known about this subject. The activity of drug-metabolizing enzymes, primarily cytochrome P450 enzymes, can determine a patient's response to a drug. Therapeutic failure or drug toxicity in the postoperative period after liver transplantation is influenced by the drug metabolizing capacity of the graft. Dose adjustment or selection of an alternative drug, which is not a substrate for the polymorphic enzyme may prevent the development of side-effects in recipients of poor metabolizer liver grafts. What this study adds. A validated analytical system with metabolomic tools has been developed to estimate the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates the improvement of individual recipient therapy. In the test of drug-metabolizing status, one of the liver grafts was found to be a CYP2C9 poor metabolizer, while the other was a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. AIMS: The drug-metabolizing capacity of transplanted liver highly influences drug efficacy or toxicity, particularly in the early postoperative period. The aim of our study was to predict therapeutic failures or severe adverse drug reactions by phenotyping for cytochrome P450 (P450) polymorphism resulting in reduced or no activity of the key drug-metabolizing enzymes. METHODS: A validated analytical system with metabolomic tools has been developed for estimation of the drug-metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates improvement of the individual recipient therapy. RESULTS: Of the 109 liver donors in Hungary, the frequency of poor metabolizers was found to be 0.92%, 5.5% and 8.3% for CYP2C9, CYP2C19 and CYP2D6, respectively. In the present study, two liver grafts transplanted in paediatric recipients were reported to be poor metabolizer phenotypes. The liver grafts presented normal function in the early postoperative days; 2 weeks after transplantation, however, increasing liver enzymes were detected. Histological investigation of a liver biopsy suggested drug toxicity. The test of drug metabolizing status showed one of the liver grafts to be a CYP2C9 poor metabolizer, and the other was found to be a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week. CONCLUSIONS: Prospective investigation of the P450 status may lead to the optimization of drug choice and/or dose for a more effective therapy, avoid serious adverse effects, and decrease medical costs. Phenotyping donor livers and tailored medication can contribute to the improvement of graft and recipient survival.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Trasplante de Hígado/efectos adversos , Hígado/enzimología , Adolescente , Adulto , Anciano , Niño , Sistema Enzimático del Citocromo P-450/genética , Femenino , Variación Genética/fisiología , Humanos , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , Preparaciones Farmacéuticas/metabolismo , Donantes de TejidosRESUMEN
UNLABELLED: The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. AIM: Authors present the results of liver transplantations performed due to HCV infection. METHOD: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. RESULTS: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence. CONCLUSIONS: An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Cirrosis Hepática/cirugía , Trasplante de Hígado , Adulto , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Hepatitis C/tratamiento farmacológico , Humanos , Interferones/uso terapéutico , Estimación de Kaplan-Meier , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Recurrencia , Reoperación , Estudios Retrospectivos , Ribavirina/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
The authors overview the results of liver transplantations of HBV patients in Hungary. The special needs of pre- and postoperative period of HBV infected patients in the treatment are discussed. 4 patients were transplanted because of HBV cirrhosis. 1 patient died in the early postoperative period, 3 patients are well and active. The authors also overview the de novo HBV infections in transplanted patients, found in 6 cases.
Asunto(s)
Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/etiología , Hepatitis B/cirugía , Trasplante de Hígado , Hígado/patología , Animales , Antivirales/uso terapéutico , ADN Viral/aislamiento & purificación , Resultado Fatal , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/patología , Virus de la Hepatitis B/genética , Humanos , Hungría , Hígado/cirugía , Hígado/virología , Cirrosis Hepática/patología , Cirrosis Hepática/cirugía , Cirrosis Hepática/virología , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Authors analyzed the differences in the outcome of two European liver transplant centers differing in case volume and experience. The first was the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the second the University Medical Center Groningen, Groningen, The Netherlands (UMCG). We investigated if such differences could be explained. The 1-, 3- and 5-year patient survival in the UMCG was 86%, 80%, and 77% compared with 65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%, and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were present regarding the donor and recipient age, diagnosis mix, disease severity and operation variables, per-operative transfusion rate, vascular complications, postoperative infection rate, and need for renal replacement. To determine factors correlating with survival, a separate uni- and multivariate analysis was performed in each center individually, between study parameters and patient survival. In both centers, peri-operative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. The difference in blood loss can be explained by different operation techniques and shorter operation time in SEB, with consequently less time spent on hemostasis. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity.
Asunto(s)
Trasplante de Hígado/métodos , Adolescente , Adulto , Anciano , Transfusión Sanguínea , Niño , Eritrocitos/metabolismo , Europa (Continente) , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Tiempo , Resultado del TratamientoRESUMEN
The authors evaluate the results of the technical variants of liver transplantion in the first 10 years. They present the technique of conventional and piggyback liver transplantation. Their aim is to compare the outcome of the two surgical implantation techniques. Using the piggyback technique, the need for intraoperative blood transfusion was less (10U) compared to conventional transplantion (15U). Vascular complication rate was lower with conventional, compared to piggy back technique. Hepatic artery thrombosis rate was higher (14% vs. 5%) while venous outflow occlusion rate was lower (0% vs. 8%) in conventional technique compared to piggyback. Postoperative kidney failure was more frequent after conventional and crossclamp technique (45%). The 1, 3, and 5 year cumulative patient survival rates were 62%, 55% and 52% in the conventional group, and 79%, 71% is 63% after piggyback. The 1, 3 and 5 years graft survival were 60%, 53% and 50% after conventional and 74%, 66% and 60% after piggyback implantation. The piggyback technique became routine standard procedure in Hungary, with lower transfusion need, less kidney failure and very good results.
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Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Adulto , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Supervivencia de Injerto , Humanos , Hungría/epidemiología , Cuidados Intraoperatorios/métodos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Insuficiencia Renal/etiología , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTIONS: The authors summarize the demographic, morbidity and mortality characteristics of the Hungarian Liver Transplant Program. AIMS: They evaluate the changes and development, that has taken place with regard to indications, recipient population and characteristics, operation technique, and peroperative patient management. METHOD: In order to present the development, data are compared between two time periods (before and after 1999). The results are summarized on Tables and statistical Figures. Categorical variables are evaluated by chi2-test, continuous ones are with Levene Test (for homogeneity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis. RESULTS: 194 primary liver transplantation have been performed. The hepatitis C was the leading indication from the beginning. Ten (10) liver transplantation have been performed in 1995, while 44 in 2004. The mortality within the first 2 months decreased from 24% to 5%. The 1, 3 and 5 year cumulative patient survival increased from 55%, 45% es 39% (1995-1997), to 72%, 64% es 61% (1998-2000). Recently this is 78%, 77% es 77%. CONCLUSIONS: Between 1995-1997 conventional liver transplantation became standard, while piggy back turned to be popular from 1998. From 1999 the HCV-PCR monitoring, the combined antiviral treatment, the UW perfusion of the donors took place. From 2003 we introduced the tailored immunosuppression, the steroid-free protocol for viral diseases. Total infused volume was decreased together with the amount of transfusion. The retrograde graft reperfusion (from the caval side) was introduced in 2004 together with the split technique in the liver transplantation and the rebirth of the pediatric program. The overall outcome of the retrospective analysis is, that the program has been developed to European standards with respect to its volume, technical capabilities and results.
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Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Adolescente , Adulto , Profilaxis Antibiótica/métodos , Niño , Preescolar , Femenino , Rechazo de Injerto/prevención & control , Humanos , Hungría/epidemiología , Terapia de Inmunosupresión/métodos , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento PretrasplanteRESUMEN
INTRODUCTION: Reperfusion injury and hepatic artery thrombosis are major causes of graft failure after liver transplantation. The magnitude of oxidative stress increases after reperfusion and the appearance of an arterial thrombosis presents a higher risk for the graft and patient survival. AIM OF THE STUDY: The aim of the study was to detect the level of oxidative stress in the perioperative period of transplantation. METHODS: Clinical documentations of 32 patients were investigated and the level of myeloperoxidase (MPO) was measured for the monitoring of the oxidative stress. RESULTS: The mean age of the patients was 43 years and hepatitis C cirrhosis was the most common indication (14 cases, 43%). Two retransplantations were done. In 24 cases (75%) the primary graft functions and patient survival were good. Eight patients died, in two cases because of acute liver failure, in two cases due to primary non function and in four cases due to late complications. The incidence of hepatic artery thrombosis was 11% (4 cases) and the incidence of acute rejection was 35% (12 cases). The level of MPO was higher (65 ng/ml) in all patients before operation. After the first 48 hours this level increased significantly (p < 0.0001) up to the mean level of 123 ng/ml and decreased after one week. In the cases with acute liver failure and hepatic artery thrombosis high levels of MPO were measured. CONCLUSION: This study provides evidence of increased oxidative stress before liver transplantation. The magnitude of these changes increased after operation, mostly in cases with acute liver failure and hepatic artery thrombosis. Reducing the reperfusion injury and performing an "ideal" arterial supply for the liver-graft present better survival.