[Living donor liver transplantation in adults. Initial results]. / Trasplante hepático en adulto de donante vivo. Resultados iniciales.

AIM: To analyze the preliminary results of the implementation of a living donor liver transplantation program. PATIENTS AND METHOD: Between March and September 2000 we performed 7 living donor liver transplantations using the right hepatic lobe. The donors were 5 men and 2 women with a mean age of 39.3 11.5 years. Three donors were genetically related (daughter, mother, son). The mean relative liver volume transplanted was 58.8 2.5%. The mean age of the recipients was 50.4 16.5 years. Six patients presented hepatitis C virus-induced cirrhosis and one presented familial amyloidotic polyneuropathy. RESULTS: Three complications occurred in the donors: 1 slight infection and 2 biliary fistulae. Graft function was adequate in all recipients and there were three acute rejections. Four biliary leakages occurred of which two required reoperation. None of the patients developed vascular thrombosis. Two recipients died, 53 and 72 days after the operation, with a correctly functioning graft. CONCLUSION: Living donor liver transplantation constitutes a necessary complement to the current cadaveric donor program to increase the number of patients who can benefit from this treatment, which may represent 10% of the activity of our center. The technical complexity of this procedure is much greater than that of cadaveric transplantation. The right hepatic lobe provides sufficient hepatic mass for most adult recipients.

Bacterial translocation of enteric organisms in patients with cirrhosis.

BACKGROUND/AIMS: The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS: Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS: Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS: Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

Ascites after liver transplantation.

Massive ascites after liver transplantation, although uncommon, usually represents a serious adverse event. The pathogenesis of this complication has not been adequately investigated. To determine the incidence, characteristics, and pathogenic factors of massive ascites after liver transplantation (ascitic fluid > 500 mL/d for >10 days), the charts of 378 liver transplant recipients were reviewed. Massive ascites occurred in 25 patients (7%). Mean ascitic fluid production was 960 mL/d (range, 625 to 2,350 mL/d), and the duration of ascites was 77 days (range, 15 to 223 days). The ascitic fluid had a high protein content (36 +/- 7 g/L; range, 25 to 50 g/L). When patients who did and did not develop massive ascites were compared, significant differences were found in receptor sex (men, 88% v 60%, respectively; P <.01) and surgical technique (inferior vena cava preservation with piggyback technique, 72% v 41%; P <.01). Significantly increased wedged and free hepatic venous pressures and gradients between hepatic vein and right atrial pressures were found in patients who developed ascites, suggesting a difficulty in graft blood outflow. Massive ascites was associated with renal impairment, increased incidence of abdominal infection, prolonged hospitalization, and a tendency toward reduced survival. In conclusion, massive ascites after liver transplantation is relatively uncommon but associated with increased morbidity and mortality and is predominantly related to difficulties of hepatic venous drainage. Measurement of hepatic vein and atrial pressures to detect a significant gradient and correct possible alterations in hepatic vein outflow should be the first approach in the management of these patients.

Hepatitis B immunoglobulin discontinuation followed by hepatitis B virus vaccination: A new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation.

It is widely agreed that hepatitis B virus immunoglobulin (HBIG) should be administered for at least 12 months to patients transplanted for hepatitis B virus (HBV)-related diseases to prevent HBV recurrence. No data are available, however, on how long this treatment should be used, and most centers currently administer HBIG on a life-long basis. Herein, we report the results of a new prophylactic strategy aiming at the discontinuation of HBIG treatment and consisting of the administration of double dose recombinant HBV vaccine (0, 1-, and 6-month schedule) to liver transplant recipients fulfilling the following criteria: (1) liver transplantation for conditions related to nonreplicative HBV infection (hepatitis B surface antigen [HBsAg] positive, hepatitis B e antigen [HBeAg] negative, and HBV DNA negative); (2) at least 18 months of HBIG administration; and (3) no HBV infection recurrence, normal or slightly altered liver graft function, and low-grade immunosuppression at the time of vaccination. Seventeen patients received HBV vaccination and 14 of them (82%) developed protective serum titers of anti-HBs (>10 IU/L). Six patients seroconverted after a first course of vaccination, whereas 8 patients required a second course (3 additional doses of vaccine). Responding patients were followed for a median of 14 months (range, 3-50) after seroconversion. During this period no HBV recurrence occurred and in only 2 patients a decrease of anti-HBs titers below 10 UI/L was observed. Our data suggest that in selected liver transplant recipients, posttransplantation HBV vaccination may be a useful and cost-effective strategy in the prophylaxis of HBV recurrence, allowing the discontinuation of life-long HBIG treatment.

Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome.

BACKGROUND: Portopulmonary hypertension and hepatopulmonary syndrome have been considered mutually exclusive pulmonary vascular disorders in liver disease states. METHODS: This current report describes a middle-aged patient, a candidate for liver transplantation, diagnosed with hepatopulmonary syndrome on the basis of clinical, echocardiographic and gas exchange criteria. Unusually high pulmonary pressures were observed at liver transplantation, performed 6 months after the initial diagnosis of hepatopulmonary syndrome. Three months later, the patient developed severe pulmonary hypertension and died of right ventricular failure during a second attempted liver transplantation. Postmortem histologic findings in the lung confirmed the presence of plexogenic pulmonary arteriopathy. CONCLUSION: This case illustrates the potential occurrence of hepatopulmonary syndrome and portopulmonary hypertension in the same patient, suggesting that the presence of hepatopulmonary syndrome may not preclude the development of portopulmonary hypertension.

Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100 ): influence of hematocrit elevation.

BACKGROUND AND OBJECTIVE: Patients with end-stage renal disease or advanced cirrhosis develop bleeding disorders characterized by defective interaction of platelets with damaged subendothelium. The anemia associated with both clinical entities has a negative influence on hemostasis. We evaluated alterations of platelet function in patients suffering from end-stage renal disease (n=21) or hepatic cirrhosis (n=20) using standard aggregometric techniques and the recently developed platelet function analyzer (PFA-100 ). The impact of low hematocrit was also analyzed. DESIGN AND METHODS: The hemostatic capacity of platelets was tested in the PFA-100 using citrated blood and standard cartridges containing collagen-ADP (COL-ADP) or collagen-epinephrine (COL-Epi). The hemodynamic influence of hematocrit was also evaluated in blood aliquots in which hematocrit was experimentally increased by adding red blood cells from the same patient. RESULTS: Aggregation studies demonstrated abnormal responses to several agonists in both group of patients. Closure times obtained by the PFA-100 for control blood samples were 87+/-3 sec for COL-ADP and 113+/-5 sec with COL-EPi cartridges. Closure times in uremic and cirrhotic patients with average hematocrits of 0.26 and 0.27 respectively were significantly prolonged (139+/-12 and 125+/-14 sec, respectively with COL-ADP and 194+/-29 and 151+/-15 sec with COL-Epi cartridges). A 5% increase in the hematocrit caused a reduction in the closure time to 111+/-7 sec (COL-ADP) and 143+/-14 sec (COL-Epi) in the uremic group and to 86+/-4 sec (COL-ADP) and 115+/-16 sec (COL-Epi) in the cirrhotic group. Our studies confirm the platelet dysfunction in uremic and cirrhotic patients. INTERPRETATION AND CONCLUSIONS: The PFA-100 device proved to be useful for testing alterations of primary hemostasis in these acquired disorders and was sensitive enough to detect modifications in hemostasis caused by elevations in hematocrit. Conventional aggregometric tests were able to identify the intrinsic platelet abnormality in uremic and cirrhotic conditions, while the PFA-100 seemed more sensitive in detecting the negative influence of the hematocrit reduction.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. METHODS: We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. RESULTS: During follow-up (12+/-17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. CONCLUSION: Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.

Effects of increasing blood hemoglobin levels on systemic hemodynamics of acutely anemic cirrhotic patients.

BACKGROUND/AIMS: In experimental portal hypertension, blood hemoglobin levels have been shown to influence the hyperdynamic circulatory state. The aim of this study was to assess the hemodynamic effects of increasing hemoglobin concentration in human portal hypertension. METHODS: Sixteen cirrhotic patients recovering from a variceal bleeding episode were randomly assigned to receive two units of packed red cells or 500 ml of a protein solution. Systemic and portal hemodynamics, and rheological and hormonal parameters were measured at baseline and after expansion. RESULTS: Both groups were similar with respect to the degree of liver failure, severity of the bleeding episode, activation of the endogenous vasopressor systems, and hemodynamic parameters. The administration of either erythrocytes or a protein solution prompted a similar increase in total blood volume and suppression of vasopressor systems. Both groups of patients experienced similar increases in wedged hepatic venous pressure. Hepatic venous pressure gradient was not significantly modified but tended to increase in erythrocyte-transfused patients. Cardiopulmonary pressures increased, but this increment was significant in the non-blood-transfused patients only. Cardiac output decreased in erythrocyte-transfused patients, while it increased in the group receiving a protein solution. Red blood cell transfusion resulted in an increase in systemic vascular hindrance (resistance/blood viscosity), whereas the administration of a protein solution prompted a decrease in this parameter, thus reflecting true vasoconstriction and vasodilation, respectively. CONCLUSIONS: An increase in blood hemoglobin in acutely anemic cirrhotic patients attenuates their hyperdynamic circulation beyond viscosity-dependent changes, an effect which might be counteracted by the effects on portal venous pressure gradient.

Liver transplantation in patients with non-biliary cirrhosis: prognostic value of preoperative factors.

BACKGROUND/AIM: The type of disease indicating liver transplantation is one of the most powerful predictors of postoperative survival. This may be an important problem in evaluating the prognostic significance of other factors when patients with liver diseases of very different nature are jointly studied. To minimize this bias, the present study aimed to investigate preoperative prognostic factors in liver transplantation only in patients with non-biliary cirrhosis. METHODS: Twenty-three preoperative standard clinical and laboratory variables were analyzed as possible prognostic factors in 162 patients receiving liver transplantation for non-biliary cirrhosis. Data for seven splanchnic and systemic hemodynamic variables were also analyzed in 55 patients. RESULTS: Using univariate analyses followed by a multivariate analysis, only preoperative blood urea nitrogen (BUN) reached statistical significance as an independent predictor of hospital survival; the survival rate at the end of hospitalization being 90% in patients with BUN< or =25 mg/dl and 65% in patients with BUN>25 mg/dl (p=0.0008). Similarly, preoperative BUN was the only variable independently predicting cumulative long-term survival, with an 87% survival probability at 1 year and 73% at 4 years in patients with BUN< or =25 mg/dl, and 61% and 49%, respectively, in patients with BUN>25 mg/dl (p=0.0014). CONCLUSIONS: Renal function parameters are the most powerful preoperative predictors of survival after liver transplantation in patients with non-biliary cirrhosis. It is suggested that liver transplantation is indicated in these patients before marked renal dysfunction develops.

Anemia worsens hyperdynamic circulation of patients with cirrhosis and portal hypertension.

This retrospective cohort study was aimed at investigating the effects of anemia on the hemodynamic disturbances associated with portal hypertension. In all, 202 consecutive nontreated portal-hypertensive patients referred for evaluation to our Hepatic Hemodynamic Laboratory were included. Compared to the nonanemic patients, anemic cirrhotic patients had an increased cardiac output (7.9 +/- 1.9 vs 7.1 +/- 2 liters/min, P < 0.01), and a decreased mean arterial blood pressure (82 +/- 11 vs 94 +/- 13 mm Hg, P < 0.0001) and systemic vascular resistance (838 +/- 235 vs 1102 +/- 356 dyn/sec/cm5, P < 0.0001). Similar results were obtained when Child A or Child B-C patients were analyzed separately. Multivariate logistic regression disclosed that hemoglobin concentration, in addition to age, sex azygos blood flow, and albumin concentration, was an independent factor influencing the degree of systemic vasodilation in cirrhotic portal-hypertensive patients. This study discloses that anemia worsens the hyperdynamic circulation associated with portal hypertension. Since hemoglobin concentration may change with time, this parameter should be taken into account when evaluating hemodynamics in portal-hypertensive patients.

[Massive pleural effusion secondary to pancreatic-pleural fistula as first manifestation of chronic pancreatitis. Report of three cases]. / Derrame pleural masivo secundario a una fístula pancreatopleural como primera manifestación de una pancreatitis crónica. Descripción de tres casos.

Patients with chronic pancreatitis develop massive pleural effusion in less than 1% and its frequency as the first clinical manifestation of the disease is unknown. Three patients with massive pleural effusion and dyspnea which led to the diagnosis of chronic pancreatitis are referred. The patients were 28, 37 and 41 years old, they were hard-drinking and they came to the hospital because of quick and progressive dyspnea, with hypoxemia and hypocapnia. Two patients had right and one left pleural effusion. The thoracothentesis gave 10, 9 and 3.5 l of serohematic liquid rich in pancreatic enzymes. All cases showed tomographic changes of chronic pancreatitis and pancreatic pseudocysts. Only in one of them the link between the pseudocyst and pleural effusion through a fistula in the right support of the diaphragm could be identified. The different therapeutic possibilities are discussed. Pancreatopleural fistula diagnosis should be considered in patients with massive fast pleural effusion and a history of high alcohol intake. High levels of pancreatic enzymes in the pleural liquid confirm the diagnosis.

Liver transplantation for alcoholic cirrhosis with anti-HCV antibodies.

The results of orthotopic liver transplantation (OLT) in patients with alcoholic liver cirrhosis (ALC) are currently similar to those obtained in patients with other indications. However, the frequent association of ALC with hepatitis C virus (HCV) infection may impair these results. We retrospectively studied the consequences of HCV infection on survival and graft function in 59 patients with ALC undergoing OLT. Patients were classified into two groups depending on their HCV serology before transplantation: group 1 comprised 24 anti-HCV-positive patients, and group 2, 35 anti-HCV-negative patients. Patient and graft survival were similar in both groups. Liver function tests 1 and 4 years after OLT showed AST and ALT values that were significantly higher in group 1 patients and post-transplant histologically proven chronic hepatitis was found in 45% and 61% of these patients at 1 and 4 years, respectively. We conclude that pretransplant HCV infection in patients with ALC does not affect survival after OLT. However, one must bear in mind the high incidence of post-transplant chronic hepatitis secondary to recurrence of HCV infection and be cautious when drawing this conclusion.

[De novo tumors in adult patients with hepatic transplant]. / Tumores de novo en pacientes adultos con trasplante hepático.

The incidence of de novo neoplasms was analyzed in 340 patients with liver transplantation who survived more than 2 months post transplantation. Sixteen (4.7%) patients developed a new tumor following transplantation. The most frequent tumor observed was a lymphoma which was detected in four patients (1.2%). In three of the four lymphomas histologic diagnosis of non Hodgkin phenotype B lymphoma was confirmed and in three patients the central nervous system was involved. The remaining tumors consisted of two cases of adenocarcinoma of the colon, papillary carcinoma of the urinary bladder and ductal breast cancer (0.6%) for each of these tumors and one case of cervical cancer, adenocarcinoma of the small intestine, Kaposi sarcoma, laryngeal carcinoma, pharyngeal carcinoma and malignant melanoma (0.3% for each tumor). None of the patients developed more than one tumor. The mean time to the appearance of the tumors was 28 months (range: 3-52 months). These results suggest that de novo neoplasms in patients with liver transplantation are relatively frequent, particularly lymphoma.

[Prolonged administration of hepatitis B hyperimmune gamma globulin in patients with liver transplantation in liver diseases caused by hepatitis B virus]. / Administración prolongada de gammaglobulina hiperinmune antihepatitis B en pacientes con trasplante hepático por hepatopatía por virus de la hepatitis B.

To prevent reinfection by the hepatitis B virus (HBV) in liver transplant patients, the administration of anti-HBV hyperimmune gammaglobulin (HBIg) was proposed. This study compares the efficacy of HBIg administration alone during the anhepatic phase of liver transplantation (group 1, 19 transplantations) with that obtained with prolonged and permanent HBIg administration (group II, 18 transplantations) in patients transplanted because of liver disease by HBV. HBIg was administered intravenously in the intrahospital phase, followed by intramuscular administration in the undefined follow up period. Thirteen patients (68%) of group 1 and 5 (28%) of group II developed post transplantation reinfection by HBV (p = 0.015). Survival of the grafts with reinfection by HBV was lower than that in grafts without reinfection (6/18, 33%, and 16/19, 84%; p = 0.002). Most grafts with reinfection by HBV were lost due to patient death as a consequence of this complication. No adverse secondary effects were found to be related with HBIg administration. In conclusion, the prolonged use of HBIg in patients undergoing liver transplantation because of liver disease by HBV reduces the risk of post transplant reinfection by HBV and is well tolerated.

Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions.

A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child-Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child-Pugh classes A or B). All the patient classes showed impaired platelet-subendothelial interactions (P < .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet-subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.