Guillermo Solórzano

Assignment of steatotic livers by the Mayo model for end‐stage liver disease

Prognosis after liver transplantation depends on a combination of recipient and donor variables. The purpose of this study is to define an allocation system of steatotic donor livers relative to recipient model for end‐stage liver disease (MELD) score. We reviewed 500 consecutive OLT, computing the MELD score for each recipient. Fatty infiltration in grafts was categorized in no steatosis, 10–30%, 30–60% and ≥60% steatosis. MELD score did not affect preservation injury and graft dysfunction, which were increased with fat content. Recipient and graft survivals lowered when increasing MELD score. Outcome in low‐risk recipients (MELD ≤9) was not altered with steatosis, except those with ≥60%. Survival functions in moderate‐risk recipients (MELD 10–19) were moderately affected with 10–30% steatosis and severely with those with >30. Exactly 30–60% steatotic grafts work poorly in high‐risk recipients (MELD ≥20), and very poorly with ≥60% steatosis. Prognosis of candidates is optimally influenced when divergence of recipient–donor risks is presented.

Effect of internal biliary drainage on plasma levels of endotoxin, cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-α), interIeukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-α, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p<0.05), TNF-α (87.5 vs. 48 pg/ml; p=0.03), and IL-6 (324 vs. 232 pg/ml;/ p<0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p=0.03), IL-6 (598 vs. 330 pg/ml; p=0.04), and endotoxin (10.6 vs. 4.8 EU/L; p=0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.RésuméLe drainage biliaire préopératoire peut améliorer les perturbations des cytokines et celles observées dans la réponse de la phase aiguë chez les patients atteints d’ictère obstructif. Cette étude, prospective, longitudinale, a consisté à étudier 24 patients atteints d’ictère obstructif, 11 d’origine bénigne, 13 d’origine maligne, avant et après traitement dans un Hôpital Universitaire de 600 lits. Les interventions comportaient toujours un drainage endoscopique interne (7 papillotomies et 17 endoprothèses). On a mesuré l’endotoxine, le facteur TNF-α, l’IL-6, la production en oxyde nitrique et la C-réactive protéine (CRP) au moment de l’admission et aux jours 2 et 7 après drainage biliaire interne. Des cultures ont été obtenues avant et au moment du drainage. Les taux d’endotoxine, de l’IL-6, du TNF-α et de la CRP étaient significativement plus élevés chez les patients atteints de cancer. Après drainage interne, les taux plasmatiques de l’endotoxine (11.4 vs. 2 EU/L; p<0.05), de TNF-α (87.5 vs. 48 pg/ml; p=0.03) et d’IL-6 (324 vs. 232 pg/ml; p<0.05) ont diminué de façon significative après drainage chez les patients atteints de cancer. Les taux d’endotoxine et des cytokines tout comme les taux plasmatiques de la CRP ont cependant augmenté au jour sept. Cette tendance a été moins marquée chez les patients porteurs d’obstruction bénigne. Les patients ayant des cultures de bile positives après drainage avaient un taux postdrainage plus élevé de CRP (115 vs. 62 mg/L; p=0.03), d’IL-6 (598 vs. 330 pg/ml; p=0.04) et d’endotoxine (10.6 vs. 4.8 EU/L; p=0.02) que ceux ayant des cultures de bile négatives. L’obstruction biliaire est associée à une augmentation des taux d’endotoxines, à une réponse de phase aiguë positive et à une élévation des cytokines plasmatiques. Après drainage biliaire, on observe une amélioration transitoire de ces altérations, même si les valeurs restaient élevées une semaine après le drainage, surtout en cas de cultures de bile positives.ResumenEn pacientes ictéricos, el drenaje biliar preoperatorio parece mejorar las atocinas y las alteraciones de respuesta de la fase aguda. En un Hospital Universitario de 600 camas, se diseñó un estudio clínico prospectivo longitudinal. Se estudiaron 24 pacientes con ictericia obstructiva: La obstrucción era benigna en 11 y maligna en 13. El drenaje biliar interno se realizó por vía endoscópica (7 papilotomías y 17 endoprótesis). El día del ingreso y a los 2 y 7 días del drenaje biliar interno se determinaron: endotoxina, TNF-α, IL-6, producción de óxido nítrico y proteína C reactiva (CRP). Las endotoxina, IL-6, TNF-α y CRP estaban significativamente más elevadas en pacientes con cáncer. En pacientes cancerosos, tras drenaje interno, los niveles plasmáticos descendieron inmediata y significativamente: endotoxina (11.4 vs. 2 EU/L; p<0.05) TNF-α (87.5 vs. pg/ml; p=0.03), y IL-6 (324 vs. 232 pg/ml; p<0.05). Sin embargo, la citocina, endotoxina y los valores plasmáticos de la CRP volvieron ha elevarse al 7° día post-drenaje. Estas modificaciones fueron menores en pacientes con ictericia obstructiva benigna. Tras el drenaje, los pacientes con cultivos biliares positivos, mostraron mayores elevaciones de la CRP (115 vs. 62 mg/L; p=0.03), IL-6 (598 vs. 330 pg/ml; p=0.04) y de la endotoxina (10.6 vs. 4.8 EU/L; p=0.02), que aquellos cuyos cultivos fueron negativos. La obstrucción del colédoco se acompaña de: un incremento de los niveles de endotoxina, respuesta positiva de la fase aguda y elevación de las citocinas plasmáticas. Tras drenaje biliar se produce una mejora transitoria de las alteraciones observadas, aunque los parámetros persisten elevados transcurrida una semana del drenaje biliar. Este hecho se observó en pacientes con cultivos positivos en la bilis.

Randomized Trial of Weekly Sulfadoxine/Pyrimethamine vs. Daily Low-Dose Trimethoprim-Sulfamethoxazole for the Prophylaxis of Pneumocystis carinii Pneumonia After Liver Transplantation

We conducted a prospective, randomized clinical trial among liver transplant patients to assess the efficacy and safety of weekly sulfadoxine/pyrimethamine compared with daily trimethoprim-sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia. The studied drugs were given during 6 months after transplantation. One hundred twenty patients were included. None of the 60 patients receiving weekly sulfadoxine/pyrimethamine developed Pneumocystis carinii pneumonia, whereas two cases (3%) developed among the 60 patients who received trimethoprim-sulfamethoxazole. For both patients, the studied medication had been discontinued several weeks earlier because of adverse effects. No differences were observed in the incidence of adverse effects. We conclude that weekly sulfadoxine/pyrimethamine is as effective and safe as is daily trimethoprim-sulfamethoxazole in the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.

Use of artificial intelligence as an innovative donor-recipient matching model for liver transplantation: Results from a multicenter Spanish study

BACKGROUND & AIMS There is an increasing discrepancy between the number of potential liver graft recipients and the number of organs available. Organ allocation should follow the concept of benefit of survival, avoiding human-innate subjectivity. The aim of this study is to use artificial-neural-networks (ANNs) for donor-recipient (D-R) matching in liver transplantation (LT) and to compare its accuracy with validated scores (MELD, D-MELD, DRI, P-SOFT, SOFT, and BAR) of graft survival. METHODS 64 donor and recipient variables from a set of 1003 LTs from a multicenter study including 11 Spanish centres were included. For each D-R pair, common statistics (simple and multiple regression models) and ANN formulae for two non-complementary probability-models of 3-month graft-survival and -loss were calculated: a positive-survival (NN-CCR) and a negative-loss (NN-MS) model. The NN models were obtained by using the Neural Net Evolutionary Programming (NNEP) algorithm. Additionally, receiver-operating-curves (ROC) were performed to validate ANNs against other scores. RESULTS Optimal results for NN-CCR and NN-MS models were obtained, with the best performance in predicting the probability of graft-survival (90.79%) and -loss (71.42%) for each D-R pair, significantly improving results from multiple regressions. ROC curves for 3-months graft-survival and -loss predictions were significantly more accurate for ANN than for other scores in both NN-CCR (AUROC-ANN=0.80 vs. -MELD=0.50; -D-MELD=0.54; -P-SOFT=0.54; -SOFT=0.55; -BAR=0.67 and -DRI=0.42) and NN-MS (AUROC-ANN=0.82 vs. -MELD=0.41; -D-MELD=0.47; -P-SOFT=0.43; -SOFT=0.57, -BAR=0.61 and -DRI=0.48). CONCLUSIONS ANNs may be considered a powerful decision-making technology for this dataset, optimizing the principles of justice, efficiency and equity. This may be a useful tool for predicting the 3-month outcome and a potential research area for future D-R matching models.

BNP as marker of heart dysfunction in patients with liver cirrhosis.

Backgrounds Patients with liver cirrhosis suffer various degrees of cardiac dysfunction which may be crucial in determining the outcome of surgery. The aim of this study was to determine the role of natriuretic peptides on the assessment of cardiac dysfunction in patients with liver cirrhosis. Methods Prospective longitudinal study of 30 patients with hepatic cirrhosis. Severity of disease was assessed according to the Child–Turcotte–Pugh and Model for End Stage Liver Disease (MELD) scores. Cardiac function was assessed using endocrine markers [atrial natriuretic peptide–brain natriuretic peptide (BNP)] and isotopic ventriculography at baseline and after stimulation with dobutamine. Results The ejection fraction was higher in patients with Child A+B and MELD less than 18 than in patients with advanced liver disease. A significant correlation between BNP plasma levels and MELD values was observed. Dobutamine induced a marked improvement in myocardial performance associated to a decrease in BNP levels. Multivariate analysis showed that BNP has prognostic value as a marker of cardiac ejection fraction. Patients whose baseline BNP concentrations were more than 70 pg/ml had an ejection fraction of around 45%. Conclusion This study has shown that increased baseline BNP concentrations may be regarded together with high Child and MELD scores, as the critical cardiac dysfunction threshold in cirrhotic patients.

Use of high-risk liver donors for urgent and elective liver transplantation.

ORGAN SHORTAGE is now the main factor limiting the growth of orthotopic liver transplantation (OLT). There is an increasing gap between need and transplantation in both the United States and in Europe. Moreover, the number of patients who benefit from this procedure has been broadened, resulting in patients who are less ill. To assure the best possible outcome, the pioneering transplant clinicians applied strict criteria when selecting potential donors, based on arbitrary medical grounds. This policy has resulted in the refusal of many potential donors, while deaths on waiting lists continue to constitute an unfortunate scenario. The use of high-risk or marginal donors is the most viable short-term means to boost the organ supply. Expansion of the liver donor pool calls for new organselection criteria. The use of older donor livers has been the most “liberalized” criterion. Other criteria such as longer hypotension and cold ischemia times, high-dose inotropic drug use, ICU stay, and morbid obesity status have recently been expanded. We have also reported the influence of unstable and hypernatremic liver donors on graft and patient survival. However, the relationship between these criteria and recipient status is poorly understood. Networks of organ-sharing worldwide aim to providing equity and efficacy of organ distribution, giving highest priority to patients most urgently in need. One major issue in organ allocation concerns which of the following options would contribute most to saving lives and improving longterm survival: (1) allocating organs according to sequence on the waiting list; (2) avoiding the confluence of risk factors from recipients and those from donors; or (3) reserving higher risk organs for higher risk recipients.

Establishment of a Pediatric Liver Transplantation Program: Experience With 100 Transplantation Procedures

OBJECTIVE To analyze the primary factors that influence the development and consolidation of a pediatric liver transplantation program. PATIENTS AND METHODS This was a retrospective study of 100 liver transplantation procedures performed in 84 pediatric patients between May 1990 and November 2007. The male-female ratio was 40:60. Mean (SD) age was 5 years (40 patients were younger than 2 years); cold ischemia time was 7.10 (3.1) hours; surgery time was 5.2 (2.2) hours; and time on the waiting list for transplantation was 75 (range, 1-1012) days. Indications for transplantation included cholestatic disease (43%), acute hepatic failure (AHF; 34%), metabolic disorders (14%), and cirrhosis (9%). Transplanted organs included 3 split grafts, 29 partial grafts, and 8 living-donor grafts. RESULTS Mean graft survival was 70.4%, 59.2%, and 58.1% at 1, 3, and 5 years, respectively. Factors that influenced graft outcome were age younger than 2 years; surgery time more than 6 hours; and AHF vs cholestatic disease, metabolic disorders, and cirrhosis. There were no significant differences in long-term (51% vs 59%) and short-term (71% vs 70%) graft survival between procedures performed in 1990-1998 compared with those performed in 1999-2007; however, there was a higher percentage (P = .005) of recipients at high risk (age younger than 2 years or with AHF) in the later period. All data were consistent with those of the European Liver Transplant Registry 2007. CONCLUSIONS A pediatric liver transplantation program can be established by a group experienced in liver transplantation.

Impacto del sistema MELD en la selección de candidatos para trasplante hepático

La tasa de mortalidad en la lista de espera de trasplante hepático se sitúa en España en torno al 10%. Sin embargo, este porcentaje puede aumentar en un 5-10% más si se añaden las exclusiones de esta lista por gravedad extrema y muy baja probabilidad de sobrevivir al trasplante, y los pacientes con hepatocarcinoma (CHC) que progresan y rebasan los límites de extensión aceptados. No existe un consenso bien definido sobre los criterios de distribución de órganos, es decir, sobre la gestión de la lista de espera, que pasa a ser un factor determinante de la tasa de mortalidad pretrasplante. Frente al modelo de priorizar a los pacientes más graves, que reduciría la mortalidad pretrasplante, se propone la selección de los candidatos con mayores probabilidades de supervivencia. La defensa de cualquiera de estas estrategias introduce sesgos de índole ética de difícil evaluación. No hay en definitiva un modelo universalmente aceptado para la distribución de donantes, de tal modo que algunos centros optan por seguir un criterio cronológico en el que, respetando el grupo sanguíneo, los pacientes son trasplantados de acuerdo con el orden de inclusión.

Trasplante hepático en pacientes con infección VIH

: During the few last years, after the introduction of high activity antiretroviral therapy (HAART), liver diseases, particularly those related to HCV infection, have emerged as one of the most important causes of mortality in patients with HIV infection. Consequently, liver transplantation is increasingly indicated in this population. Post-transplantation survival in HIV-positive patients with non-hepatitis C virus (HCV) liver diseases is adequate and similar to that in HIV-negative patients. In contrast, survival in patients coinfected with HIV and HCV is only moderate (around 50% at 5 years after transplantation). The main cause of mortality in these patients is HCV recurrence. In almost all patients, HIV infection remains controlled with HAART after liver transplantation. Other issues of interest in this setting are the selection of liver transplantation candidates and the frequent interactions between HAART and immunosuppressive drugs.