Management of liver transplantation waiting list for decompensated cirrhosis in a Spanish tertiary hospital: differences between hepatitis C virus recipients and other etiologies.

BACKGROUND: Decompensated cirrhosis due to hepatitis C virus (HCV) is one of the main indications for liver transplantation (LT) in Spain. Recurrence of HCV after LT is the main cause of graft loss and death in HCV-positive recipients. Advanced donor age determines a more aggressive recurrence of HCV and a shorter survival. In this setting, in our liver unit, grafts from younger donors are allocated to HCV-positive recipients. The aim of this study was a comparative analysis of allocation of grafts in HCV-positive recipients versus other etiologies and the impact on waiting list time, Model for End-Stage Liver Disease (MELD) score progression until LT, need of admission in a hospital, survival until LT. METHODS: This was a retrospective study from the cohort of patients included in the waiting list for LT owing to decompensated cirrhosis in the Hospital Gregorio Marañón from January 2008 to June 2013. RESULTS: A total of 91 patients were included; 63 patients (69.23%) received LT; 19 (20.88%) retired from the waiting list: 6 because of improvement, 11 (12.08%) because of death. In both groups, the age of recipients was similar (HCV 52 y vs other 53 y; P = .549). HCV patients were included in the waiting list with lower MELD score than other etiologies (HCV 16.1 vs other 19.4; P = .010); nevertheless, MELD score was similar at the time of LT in both groups (HCV 18.9 vs other 19.4; P = .675). Time on waiting list was significantly longer in HCV patients (198 d vs 86 d; P = .002) and they were admitted in hospital more days (30 d vs 12 d; P = .03). Donor age in the HCV group was significantly lower (64.3 y vs 54.7 y; P = .006). The intention-to-treat survival analysis did not show differences between the groups (log rank = 0.504). CONCLUSIONS: HCV patients with decompensated cirrhosis receive grafts from younger donors. HCV patients remain waiting longer for an optimal organ and suffer MELD deterioration and more days admitted in hospital. These differences in allocation of grafts did not affect final survival. In our experience, designating younger organs to HCV-positive patients does not penalize neither HCV recipients nor recipients with other etiologies.

Utilidad del MARS en el tratamiento de las enfermedades hepáticas / No disponible

No disponible

Tumoral response factors after radiofrequency ablation of hepatocellular carcinoma in cirrhotic liver.

OBJECTIVE: Hepatocellular carcinoma (HCC) ablation by radiofrequency (RFA) is a novel technique with a great variety of methods whose efficacy and predictive factors have not been completely studied. Some of the main predictive factors in this type of treatment are analyzed in the present study. PATIENTS AND METHODS: Ninety-three patients with hepatocellular carcinoma over cirrhosis, and with no indication for surgical resection were treated by RFA. Two different types of electrodes were used for RFA (refrigerated-"Cool-Tip" and perfusion with saline solution, the approach was percutaneous, by laparoscopy or laparotomy. RESULTS: Overall survival at 1, 2 and 3 years was 88, 81, and 76%, with a free-disease survival (FDS) of 66, 31 and 17%, respectively. For tumors less than 3 cm, FDS at 1,2 and 3 years was 74, 44 and 30%, while for more than 3 cm in size FDS was 55, 12 and 0% (p = 0.02). FDS for HCC with one nodule was 70, 36 and 22%, and for more than one nodule it decreased to 50, 17 and 0% at 1, 2 and 3 years, respectively (p = 0.07). Surprisingly, the method employed for RFA has a main influence in FDS, with 0% at 3 years for perfusion electrodes and 26% for cool-tip electrodes at the same period. CONCLUSIONS: In this series, overall survival at three years was relatively high; however, tumoral size, number of nodules and RFS method were independent variables associated with disease-free survival.

[Genetic susceptibility to the development of acute alcoholic hepatitis: role of genetic mutations in dehydrogenase alcohol, aldehyde dehydrogenase and cytochrome P450 2E1]. / Susceptibilidad genética al desarrollo de hepatitis alcohólica aguda: papel de las mutaciones genéticas en alcohol deshidrogenasa, aldehído deshidrogenasa y citocromo P450 2E1.

OBJECTIVE: Analyze the frequencies of genetic mutation in alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1) and establish their possible association with the development of acute alcoholic hepatitis (AAH). METHODOLOGY: Case-control study in a total of 85 Spanish patients. We distinguish three groups (one case group and two control groups) based on hepatic histological lesion and alcohol consumption: controls (group 1: teetotalers; group 2: drinkers without AAH; cases: group 3: drinkers with AAH). Case diagnosis was established based on the presence of polymorphonuclear leukocyte infiltrate in histological study. We analyzed the presence of the genetic mutations R47H and R369C (ADH2), E487K (ALDH2) and mutation Rsa I of CYP2E1 (allele c2) by polymerase chain reaction (PCR) and capillary electrophoresis. RESULTS: The allele c2 of CYP2E1 was found in 10%, 16% and 50% of the groups 1, 2 and 3 patients, respectively. Presence of the mutation Rsa I showed influence on the development of AAH (odds ratio [OR]: 3.63; confidence interval (95% [CI]: 0.88-15.02). CONCLUSIONS: The data suggest a possible association between the presence of the Rsa I of CYP2E1 and the development of AAH in patients with chronic alcohol consumption.

Susceptibilidad genética al desarrollo de hepatitis alcohólica aguda: papel de las mutaciones genéticas en alcohol deshidrogenasa, aldehído deshidrogenasa y citocromo P450 2E1 / Genetic susceptibility to the develpment of acute alcoholic hepatitis: role of genetic mutations in dehydrogenae alcohol, aldehyde dehydrogenase and cytochrome P450 2E1

Objetivo. Analizar las frecuencias de mutaciones genéticas en alcohol deshidrogenasa (ADH), aldehído deshidrogenasa (ALDH) y citocromo P450 2E1 (CYP2E1) y establecer su posible asociación con el desarrollo de hepatitis alcohólica aguda (HAA). Metodología. Estudio de casos-control en un total de 85 pacientes españoles. Distinguimos tres grupos (un grupo de casos y dos grupos control) en función de lesión histológica hepática y consumo de alcohol: controles (grupo 1: abstemios; grupos 2: bebedores sin HAA; casos: grupo 3: bebedores con HAA). El diagnóstico de caso se estableció en base a la presencia de infiltrado de leucocitos polimorfonucleares en el estudio histológico. Analizamos mediante reacción en cadena de la polimerasa (PCR) y electroforesis capilar la presencia de las mutaciones genéticas R47H y R369C (ADH2), E487K (ALDH2) y la mutación Rsa I de CYP2E1 (alelo c2). Resultados. El alelo c2 de CYP2E1 se halló en el 10%, 16% y 50% de los pacientes de los grupos 1, 2 y 3, respectivamente. La presencia de la mutación Rsa I mostró influencia sobre el desarrollo de HAA (odds ratio [OR]: 3,63; intervalo de confianza [IC] del 95%: 0,88-15,02). Conclusiones. Los datos sugieren una posible asociación entre la presencia de la mutación Rsa I de CYP2E1 y el desarrollo de HAA en pacientes con consumo crónico de alcohol

Objective. Analyze the frequencies of genetic mutation in alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1) and establish their possible association with the development of acute alcoholic hepatitis (AAH). Methodology. Case-control study in a total of 85 Spanish patients. We distinguis three groups (one case group and two control groups) based on hepatic histological lesion and alcohol consumption: controls (group 1: teetolaers; group 2: drinkers without AAH; cases: group 3: drinkers with AAH). Case diagnosis was established based on the presence of polymorphonuclear leukocyte infiltrate in histological study. We analyzed the presence of the genetic mutations R47H and R369C (ADH2), E487K (ALDH2) and mutation Rsa I of CYP2E1 (allele c2) by polymerase chain reaction (PCR) and capillary electrophoresis. Results. The allele c2 of CYP2E1 was found in 10%, 16% and 50% of the groups 1, 2 and 3 patients, respectively. Presence of the mutation Rsa I showed influence on the development of AAH (odds ratio [OR]: 3,63; confidence interval (95% [CI]: 0,88-15,02). Conclusions. The data suggest a posibble association between the presence of the Rsa I of CYP2E1 and the development of AAH in patients with chronic alcohol consumption

Factores de respuesta tumoral tras ablación mediante radiofrecuencia del carcinoma hepatocelular sobre cirrosis / Tumoral response factors after radiofrequency ablation of hepatocellular carcinoma in cirrhotic liver

Objetivo: la ablación por radiofrecuencia del hepatocarcinoma(ARF) es una técnica de reciente adquisición, cuya eficacia yfactores predictivos no han sido suficientemente evaluados. Elpresente estudio fue diseñado para este análisis.Pacientes y métodos: se han tratado 93 pacientes con hepatocarcinomasobre hígado cirrótico sin criterios de resección nide trasplante hepático. El tratamiento se realizó mediante abordajepercutáneo, laparoscópico o mediante laparotomía con dos tiposde electrodos de radiofrecuencia, electrodo refrigerado y deperfusión respectivamente.Resultados: la supervivencia global a los 1, 2 y 3 años fue del88, 81 y 76%, con una supervivencia-libre de enfermedad (SLE)de 66, 31 y 17% respectivamente. El análisis multivariante demostrótres variables predictivas independientes: tamaño tumoral( 3 cm; SLE a 1,2 y 3 años de 74, 44 y 30%,frente a 55, 12 y 0%; HR= 2,02; IC 95% 1,10-3,70; p = 0,02),número de nódulos (uno frente a más de uno; SLE a 1,2 y 3 añosde 70, 36 y 22, frente a 50, 17 y 0%; HR= 1,92 IC 95% 0,95-3,93; p = 0,07) y tipo de electrodo (refrigerado frente a perfusión;SLE 80, 43 y 26% a 1, 2 y 3 años frente a 49, 12 y 0%;HR = 2,06; IC 95% 1,12-3,79; p = 0,02).Conclusiones: a pesar de que la ARF proporciona una supervivenciaglobal aceptable, la SLE es notablemente inferior. El tamañodel tumor, el número de nódulos y el tipo de electrodo deARF fueron variables independientes asociadas a la SLE

Objective: hepatocellular carcinoma (HCC) ablation by radiofrequency(RFA) is a novel technique with a great variety ofmethods whose efficacy and predictive factors have not beencompletely studied. Some of the main predictive factors in thistype of treatment are analyzed in the present study.Patients and methods: ninety-three patients with hepatocellularcarcinoma over cirrhosis, and with no indication for surgicalresection were treated by RFA. Two different types of electrodeswere used for RFA (refrigerated-“Cool-Tip” and perfusion withsaline solution, the approach was percutaneous, by laparoscopyor laparotomy.Results: overall survival at 1, 2 and 3 years was 88, 81, and76%, with a free-disease survival (FDS) of 66, 31 and 17%, respectively.For tumors less than 3 cm, FDS at 1,2 and 3 years was74, 44 and 30%, while for more than 3 cm in size FDS was 55,12 and 0% (p = 0.02). FDS for HCC with one nodule was 70, 36and 22%, and for more than one nodule it decreased to 50, 17and 0% at 1, 2 and 3 years, respectively (p = 0.07). Surprisingly,the method employed for RFA has a main influence in FDS, with0% at 3 years for perfusion electrodes and 26% for cool-tip electrodesat the same period.Conclusions: in this series, overall survival at three years wasrelatively high; however, tumoral size, number of nodules andRFS method were independent variables associated with diseasefreesurvival

Sistemas de soporte hepático artificial: estado actual del tratamiento con diálisis de albúmina (MARS) / Artificial liver support systems: update on albumin dialysis (MARS)

La mortalidad de los pacientes con insuficiencia hepática sigue siendo inaceptablemente elevada. La insuficiencia hepática crónica agudizada tiene casi tan mal pronóstico como el fallo hepático agudo, de forma que es fundamental el desarrollo de sistemas que permitan el soporte de la función hepática, bien hasta el trasplante hepático o bien hasta la recuperación de la situación presente antes del daño agudo. La diálisis de albúmina es un sistema de soporte hepático artificial que permite la detoxificación de sustancias ligadas a la albúmina y de sustancias hidrosolubles, con lo que mantiene la homeostasis del paciente. La experiencia clínica actual todavía es limitada, si bien se ha demostrado que presenta efectos beneficiosos sobre parámetros clínicos, analíticos y hemodinámicos. El desarrollo de este sistema en un futuro pasa por la realización de estudios controlados multicéntricos que evalúen su efecto sobre la supervivencia en distintas afecciones

Mortality among patients with liver insufficiency continues to be unacceptably high. The prognosis of patients with acute episodes of chronic liver insufficiency is almost as poor as that of patients with acute liver failure. Therefore, systems that support liver function, either until liver transplantation can be performed or until resolution of the situation before acute injury occurs, are essential. Albumin dialysis is a system of artificial liver support that allows detoxification of albumin-related and hydrosoluble substances, thus maintaining the patient's homeostasis. Current clinical experience of this therapy is still limited, although beneficial effects on clinical, laboratory and hemodynamic parameters have been demonstrated. Multicenter, controlled trials to evaluate the effect of this therapy on survival in distinct diseases are

[Artificial liver support systems: update on albumin dialysis (MARS)]. / Sistemas de soporte hepático artificial: estado actual del tratamiento con diálisis de albúmina (MARS).

Mortality among patients with liver insufficiency continues to be unacceptably high. The prognosis of patients with acute episodes of chronic liver insufficiency is almost as poor as that of patients with acute liver failure. Therefore, systems that support liver function, either until liver transplantation can be performed or until resolution of the situation before acute injury occurs, are essential. Albumin dialysis is a system of artificial liver support that allows detoxification of albumin-related and hydrosoluble substances, thus maintaining the patient's homeostasis. Current clinical experience of this therapy is still limited, although beneficial effects on clinical, laboratory and hemodynamic parameters have been demonstrated. Multicenter, controlled trials to evaluate the effect of this therapy on survival in distinct diseases are needed.

[Liver abscess and Crohn' disease. Report of 3 cases]. / Absceso hepático y enfermedad de Crohn. Presentación de 3 casos.

Liver abscess is a rare complication of Crohn's disease. Its prevalence and mortality are higher in patients with Crohn's disease than in the general population. Owing to its nonspecific clinical presentation, which may be mistaken for reactivation of Crohn's disease or be masked by simultaneous steroid therapy, a high index of suspicion is required for an early diagnosis and prompt treatment. We report 3 cases of Crohn's disease complicated with liver abscess in which the only common features were the absence of clinical or even endoscopic activity of Crohn's disease at diagnosis and the presence of an anastomotic leak due to right ileocolectomy in the previous year. In all patients, outcome was satisfactory with antibiotic therapy and percutaneous catheter drainage.

[Indications and therapeutic possibilities of albumin dialysis (MARS)].

Despite remarkable medical advances during the last few years, liver failure--both acute and chronic--still results in high mortality. Since liver transplant programs were developed to improve survival in numerous hepatic end-stage disorders, fewer than 15% of patients with liver failure do actually receive a transplantation, be it because of the presence of procedural contraindications (toxic habits, age, concurrent disease), or of clinical conditions that may render surgery more difficult or worsen transplant prognosis. All these circumstances encouraged the development of alternative procedures to increase liver graft availability, as is the case of liver partition techniques and living-donor transplantation. On the other hand, organ scarcity for transplantation during the 1960s encouraged the parallel development of liver support systems in an attempt to reduce mortality and to improve patient survival while waiting for a transplant. Such systems attempt to replace a number of synthesis and detoxification functions for the damaged liver parenchyma. During the past few years both bioartificial systems--also referred to as "bioartificial livers"--based on bioreactors containing functionally active living hepatocytes, and extracorporeal liver detoxification systems have been developed. The latter type includes the so-called MARS (molecular adsorbent recirculating system) system, which combines albumin-bound molecule clearance and novel dialysis membrane biocompatibility.

[Aneurysms of the splenic artery in patients with liver transplantation]. / Aneurismas de la arteria esplénica en pacientes con trasplante hepático.

Splenic artery aneurysms (SAA) are not uncommon in patients with hepatic transplant (HT). Three in 150 transplanted patients in our institutions were diagnosed with SAA and two of them had a spontaneous rupture. In two patients embolization with interventionist radiology was performed with excellent results. SAA should be investigated before and after HT and be treated with embolization as soon as possible because of the high risk of rupture.

[Arterial revascularization of liver graft with PTFE vascular prosthesis]. / Revascularización arterial de injerto hepático con prótesis vascular de PTFE.

When the hepatic artery is not available in liver transplantation because of its bad quality or low flow, arterial grafts from the donor have to be used to obtain arterial blood flow from the aorta. The case of use of a vascular PTFE prosthesis when no vascular grafts were available is presented, with good outcome 6 months after transplantation.

[Ischemic hepatitis following liver biopsy in a patient with transplanted liver]. / Hepatitis isquémica tras biopsia hepática en paciente transplantada hepática.

We report a case of ischemic hepatitis following a percutaneous liver biopsy in a 51 year old female patient, who had had an orthotopic liver transplant 6 months before. The angiographic study demonstrated a marked stenosis in the hepatic artery at the anastomosis site and a small arterioportal fistula. We suggest that the percutaneous liver biopsy was partially responsible for the ischemic hepatitis, due to the development of a small arterioportal fistula in a previously damaged vascular area with hepatic artery stenosis.

[The response to hepatitis B vaccine prior to orthotopic liver transplantation]. / Respuesta a la vacuna de la hepatitis B previa al trasplante hepático ortotópico.

UNLABELLED: HBV hepatitis is a severe complication of orthotopic liver transplantation (OLT) due to the immunosuppression therapy. OBJECTIVES: The aim of this study is to evaluate the efficacy of the active HBV immunization on these patients before OLT. PATIENTS AND METHODS: This was a prospective trial, with 34 patients (20 M and 14 F), that received a double dose (40 micrograms) of HBV surface proteic Ag, on the 0th, 30th and 60th days of the study and posterior control of anti-HBs levels. If there wasn't a response, they received two more doses on the 90th and 120th days. RESULTS: There was a seroconversion in 22 patients (64.7%). Chronic alcoholism determined a lower rate of response than other etiologies (p < 0.05); this was the same in HCV chronic liver disease (p < 0.01). During their follow up, two patients had acute HBV hepatitis: one of them presented a negative response from the beginning, and in the other, anti-HBs developed transiently, when the HBV markers appeared. CONCLUSIONS: Previous HBV active immunization in OLT patients with double dose in a quick sequence, determined a positive response in a high number of patients with a higher rate of seroconversion than in other studies. The response was not so high in patients with chronic alcoholism or HVC chronic liver disease. We conclude that HVB vaccination should be done in these patients.

[The liver transplant program of the Hospital General Universitario Gregorio Marañón: an analysis of the first 100 patients]. / Programa de trasplante hepático del Hospital General Universitario Gregorio Marañón: análisis de los 100 primeros pacientes.

During a 3-year period between 1990 and 1993, 100 patients received orthotopic liver transplantation at the "Gregorio Marañón" University General Hospital. The mean age of the patients was relatively high (46.9 +/- 10 years), with an important number of cirrhotic patients (91%). The rate of primary liver failure was relatively low (4.5% of transplantations) although 12 cases with more than 55 years were included in the present series. Eleven retransplantations were performed, 8 for early failure of the graft and 3 for chronic failure. Postoperative complications of the graft were vascular in 9 cases, biliary in 17 cases, and acute rejection (cellular) in 70 patients, although only 50 of these patients required treatment with steroid boluses. Infections were diagnosed in 60 cases with 80% of major infections, 6 of them caused by Aspergillus fumigatus that were lethal in all the cases. Postoperative survival was 82%, 72%, 69% and 69% at 1 month, 6 months, 1 year and 2 years respectively.

[Mixed cryoglobulinemia associated with hepatitis C virus]. / Crioglobulinemia mixta asociada al virus de la hepatitis C.

We report six cases of essential mixed cryoglobulinemia associated with chronic liver disease and positive HCV markers, who showed several acute symptoms of vasculitis, arthralgias, neuropathy and glomerulonephritis. The presence in the serum and cryoprecipitates of anti HCV antibodies detected by the second-generation ELISA (ELISA 2) and the of HCV RNA by PCR in the serum in all six cases, suggest an important role for this virus in the pathogenesis of mixed cryoglobulinemia.

[Resection of recurrent hepatocarcinoma on a transplanted liver]. / Resección de hepatocarcinoma recidivante sobre hígado trasplantado.

Recurrence of hepatocellular carcinoma is rarely treated by surgical resection and has not been reported in the main series of liver transplantation. In this paper we present the case of a patient transplanted for hepatocellular carcinoma on cirrhosis who developed a tumoral recurrence in the transplanted liver four months later. The new tumor was removed by hepatectomy and the patient is free of tumor 24 months after resection. Surgical resection should be considered a treatment of tumoral recurrence after liver transplantation as is done after hepatectomy.