Rescue of Discarded Grafts for Liver Transplantation by Ex Vivo Subnormothermic and Normothermic Oxygenated Machine Perfusion: First Experience in Spain.

BACKGROUND: Ex vivo machine perfusion (MP) has been reported as a possibly method to rescue discarded organs. The main aim of this study was to report an initial experience in Spain using MP for the rescue of severely marginal discarded liver grafts, and to, secondarily, define markers of viability to test the potential applicability of these devices for the real increase in the organ donor pool. METHODS: The study began in January 2016. Discarded grafts were included in a research protocol that consisted of standard retrieval followed by 10 hours of cold ischemia. Next, either normothermic (NMP) or controlled subnormothermic (subNMP) rewarming was chosen randomly. Continuous measurements of portal-arterial pressure and resistance were screened. Lactate, pH, and bicarbonate were measured every 30 minutes. The perfusion period was 6 hours, after which the graft was discarded and evaluated as potentially usable, but never implanted. Biopsies of the donor and at 2, 4, and 6 hours after ex vivo MP were obtained. RESULTS: A total of 4 grafts were included in the protocol. The first 2 grafts were perfused by NMP and grafts 3 and 4 by subNMP. The second and third grafts showed a clear trend toward optimal recovery and may have been used. Lactate dropped to levels below 2.5 mmol/L with stable arterial and portal pressure and resistance. Clear biliary output started during MP. Biopsies showed an improvement of liver architecture with reduced inflammation at the end of the perfusion. CONCLUSION: This preliminary experience has demonstrated the potential of MP devices for the rescue of severely marginal liver grafts. Lactate and biliary output were useful for viability testing of the grafts. The utility of NMP or subNMP protocols requires further research.

Prevalence and Predictors of Metabolic Syndrome After Liver Transplantation.

BACKGROUND: The development of metabolic syndrome (MS) after liver transplantation (LT) is a major source of mortality derived from cardiovascular events. The aim of the present study was to determine the prevalence and risk factors of MS after LT. METHODS: One-hundred seventy-four consecutive LT patients from January 2004 to June 2010 surviving longer than 1 year after LT were included. Median follow-up after LT was 48 months. Independent predictors of MS were obtained by means of multivariate logistic regression. RESULTS: At 3 years after LT, 25.5% of patients reached a body mass index (BMI) ≥30 kg/m2, 35.6% of patients developed arterial hypertension, 54.2% showed impaired fasting glucose, 22.5% had serum cholesterol >200 mg/dL, and 22.5% showed hypertriglyceridemia >150 mg/dL. The prevalence of MS ranged from 49% to 86% depending on the considered period. The pre-LT variables associated with MS were age at LT (odds ratio [OR], 1.08; P = .002), BMI of recipient before LT (OR, 1.23; P = .001), serum glucose (OR, 1.02; P = .005), and non-heart-beating donor (OR, 1.02; P = .046). The post-LT predictors of MS were body weight (OR, 1.04; P = .005), arterial hypertension (OR, 1.02; P = .047), and serum glucose (OR, 1.02; P = .011) at 6 months. CONCLUSIONS: LT patients develop MS in a high proportion and progressively despite current efforts (ie, lifestyle modifications and aggressive management of hypertension, diabetes, and hyperlipidemia). The associated risk factors include age, increased BMI, and pre- and post-LT glucose.

Analysis of the recurrence of hepatitis C virus after liver transplantation: results of the Andalusian liver registry.

OBJECTIVE: This study analyzed the factors related to recurrence of hepatitis C virus (HCV) among orthotopic liver transplantation (OLT) patients. PATIENTS AND METHODS: We undertook a multicenter, prospective, observational study of OLT patients transplanted due to HCV at four Andalusian transplantation centers from 2005 to 2007. Patients were excluded if their survival was less than 1 month. The analysis included 110 pre-, peri-, and posttransplant variables that could affect HCV recurrence. We also examined the influence of cardiovascular risk factors and immunosuppression on HCV. RESULTS: Among 121 HCV patients, 83 (69%) experienced a histologically significant recurrence of HCV, including 13 (16%) who died compared with 5 of 38 (13%) who did not show a severe recurrence of HCV (P = .3). The mean follow-up was 44 months (range, 4 to 64 months). The mean time to appearance of the relapse was 9 months (range, 1 to 40 months) with no differences according to the type of immunosuppression. Of all study variables, donor age (> 52 years) showed a trend for greater recurrence (P = .1). The use of powerful immunosuppression (three or more drugs), either as induction or as sustained therapy, during the first posttransplantation year was significantly associated with a greater relapse rate (P < .01), albeit with no significant difference according to the type of calcineurin inhibitor. Mycophenolate mofetil was not associated with a greater posttransplantation viral load or earlier relapse, although its use in multiple immunosuppression schedules was associated with a greater relapse rate (P < .01). Survival of patients with recurrent HCV was reduced, although not significantly. Multivariate analysis showed a 4.4 times greater risk for developing de novo diabetes mellitus (DM) among patients with a severe relapse of HCV. CONCLUSIONS: There was an important trend toward a greater recurrence rate of HCV among patients who received powerful immunosuppression protocols, particularly during the first 12 months. Special attention should be given to the risk for de novo DM among HCV-positive patients.

Biliary complications after liver transplantation using side-to-side choledochocholedochostomy reconstruction with or without T-tube.

BACKGROUND: Biliary complications are a frequent cause of morbidity, graft loss, and death after orthotopic liver transplantation (OLT). The choledochocholedochostomy anastomosis without a T-tube is controversial, as it has been related to more biliary complications. AIMS: The aims of this study were to determine the incidence and to identify the risk factors of post-OLT biliary complications after reconstruction with or without a T-tube. MATERIALS AND METHODS: Ninety-five consecutive adult patients with deceased donor liver transplantations (overall survival rate, 86.3%; mean follow-up, 22.2 months) were analyzed to determine the incidence and type of biliary complications in 2 groups: choledochocholedochostomy with (45 patients, Group I) or without a T-tube (50 patients, Group II). The incidence of biliary complications in Groups I and II was 40% (18/45) and 30% (15/50), respectively (P > .05). In Group I, 49% of the complications were directly related to the T-tube. Biliary anastomosis stricture was more frequent in Group II (28% vs 8.9% in Group I; P = .018). Endoscopic retrograde cholangiopancreatography (ERCP) was the most common therapeutic procedure for the resolution of biliary complications in both groups (Group I, 66.5%; Group II, 58.2%). Arterial thrombosis, high pretransplantation Model for End-Stage Liver Disease (MELD) score, and donor obesity were identified as risk factors for biliary complications after OLT. CONCLUSION: OLT biliary reconstruction without a T-tube is not related to an increased risk of biliary complications, although stricutre of the anastomosis is more frequent in this group of patients. Donor obesity, arterial thrombosis, and high pretransplantation MELD score are associated with a higher incidence of biliary complications after OLT.

Influence of mycophenolate mofetil on preservation of kidney function in liver transplant patients.

BACKGROUND: There are numerous studies on the effect of immunosuppressive therapy with mycophenolate mofetil (MMF) on preservation of kidney function in liver transplant (OLT) patients with chronic kidney damage. However, we have noted few studies that evaluate the role of this drug prescribed from induction on kidney function. PATIENTS AND METHODS: This prospective observational multicenter study included 296 OLT performed from 2005 to 2007. The collected variables were; gender, and age, Child-Pugh stage, Model for End-Stage Liver Disease (MELD) score, transplant indication, induction immunosuppressive therapy, and baseline and 1 year posttransplant values of creatinine and glomerular filtration rate. Patients were classified into 4 groups: group 1 received MMF from induction; group 2 was never treated with MMF; group 3 started MMF in the first month posttransplant, and group 4 started MMF therapy in the third month posttransplant. We used Wilcoxon and Mann-Whitney U statistical tests. RESULTS: There was a difference of 0.18 mg/dL in baseline creatinine values between groups 1 and 2 (P < .01). However, although patients who consistently had MMF in their treatment started with worse creatinine values, they were able to maintain them within normal ranges at 12 months. In contrast, patients in group 2 showed a significant worsening of 0.28 mg/dL in the first month that persisted throughout the study. Group 3 displayed worse baseline creatinine values than group 2 (P < .05), and also suffered an increase of 0.29 mg/dL (P < .01) versus baseline at 1 month. When MMF was added to their immunosuppressive therapy, the creatinine values reduced versus 1 month by 0.18 mg/dL (P < .05). Creatinine values remained stable at the other study assessments. Group 4 showed a normal creatinine value at baseline, but were altered at 1 and 3 months (P < .01), with increases versus baseline of 0.46 and 0.35 mg/dL, respectively. However, when MMF was introduced kidney function was restored and maintained over the study. CONCLUSION: Early introduction of MMF improved creatinine values among patients with impaired kidney function, maintaining them at stable levels. Furthermore, patients with altered creatinine values at baseline did not worsen their kidney function if they receive MMF from induction.

Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence.

OBJECTIVE: The goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of post-transplant tumor relapse and factors related to this complication. DESIGN: Retrospective study of a consecutive series of patients having had liver transplant for HCC. PATIENTS AND METHODOLOGY: Transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. RESULTS: The survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR=1,7944) (IC 95%=1,1332-2,8413) and the vascular invasion (OR=6,6346) (IC 95%=1,4624-30,1003) as risk factors of relapse. CONCLUSIONS: The liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion.

[Early-onset acute toxic hepatitis induced by intravenous amiodarone administration]. / Hepatitis tóxica aguda de instauración precoz por amiodarona intravenosa.

Amiodarone is a widely used and effective long-term antiarrhythmic drug but with known adverse effects. Prolonged oral administration of this drug has been implicated in numerous hepatic lesions, ranging from isolated, asymptomatic transaminase elevation to fulminant, fatal liver failure. Few cases of acute hepatotoxicity due to intravenous administration have been reported. We present a 69-year-old woman with atrial fibrillation who developed acute hepatitis within 24 hours of amiodarone infusion at the recommended dosage. The drug was withdrawn and laboratory findings progressively returned to normal over the following days. We analyze a possible mechanism of action for hepatotoxicity and highlight the importance of monitoring liver function in patients receiving this drug.

[Prognostic factors in liver transplantation. Is the lidocaine test usefull?]. / Factores pronósticos en el trasplante hepático. Es útil el test de lidocaína?

UNLABELLED: With continuous development of liver transplantation, the need of better tests for selecting donors and improving diagnosis of postransplant hepatic dysfunction, is increasing. OBJECTIVE: To determine the prognostic value of a number of parameters, including the lidocaine test (MEGX) in selecting donors, and assessing the efficacy of this test in the postransplant follow-up as an indicator of morbidity and mortality. METHODS: A consecutive series of forty donor-receptor pairs was studied for six months postransplant. In addition to the lidocaine test, different clinical, analytical and histological variables were analysed. Death, retransplantation, graft dysfunction and days in hospital were considered as indicators of morbimortality. RESULTS: Among the variables selected by univariate analysis, only ALT value at day 1 and Child-Pugh score at day 7 reached independent prognostic value in a Cox's regression model. However, both a cut-off level of 50 ng/ml for MEGX in donors and 40 ng/ml for MEGX test at day 1 postransplant, allowed to identify statistically different survival curves (p < 0.05). The lidocaine test at day 7 showed a significant association with the number of rejection episodes. CONCLUSIONS: ALT value at day 1 and Child-Pugh score at day 7 turned out to be the only variables with independent prognostic value for survival during the first six months postransplant. The MEGX value may be of help in selecting donors and a subgroup of receptors (day 1 < 40 ng/ml) with a high risk of mortality.

[Comparison of 2 treatment strategies with prednisone and interferon in chronic hepatitis B]. / Comparación de dos esquemas de tratamiento con prednisona interferón en la hepatitis crónica por virus B.

Twenty patients with chronic B hepatitis and viral replication were included in a randomized study comparing the efficacy of sequential treatment with prednisone for 6 weeks followed by alpha-2a interferon (IFN) for 6 months (group A, 9 cases), versus concomitant administration of both drugs (group B, 11 cases). There were no significant differences between the two groups regarding age, sex, AST, ALT, DNA-VHB values, index of histological activity or type of underlying chronic hepatitis. Two patients from each group were excluded. The mean follow-up of the patients was 22.2 months. In group A, four responses were achieved (57.1%), of which 2 were complete and 2 partial. The overall response rate in group B was 77.7% (7 cases), 6 of them were complete responses (66.7%). Among HBsAg-positive patients from group B, one seroconverted to anti-HBs. A total of 7 patients with anti-HBe were included in the study. Two belonged to group A, in which a partial response was achieved, and another 5 were in group B, with 4 reaching a complete response and one reaching a partial response. There were no statistical differences with regards to the type of response in both groups. The AST, ALT values, as well as the pre-treatment levels of DNA-VHB, showed a significant statistical association with the response (p < 0.05). In all patients responding to treatment a histological improvement was observed that became even more evident in the biopsy performed 12 months after IFN withdrawal. In conclusion, concomitant therapy with prednisone and IFN is as effective as sequential therapy in the treatment of chronic B hepatitis. The results achieved with concomitant therapy suggest that new controlled trials are need to establish if this therapeutic schedule is the elective treatment in chronic B hepatitis.

[An analysis of a general prospective series of 3270 upper digestive hemorrhages]. / Análisis de una serie general prospectiva de 3,270 hemorragias digestivas altas.

The results of a global (general series of 3,270 episodes of upper gastrointestinal haemorrhage (UGH) admitted to our unit between the 15th of April 1983 and the 15th of April 1988 have been analyzed. All the patients entered a prospective protocol with 29 variables. Diagnostic and therapeutic approaches had previously been defined. The incidence of UGH in this area was 160 bleeding episodes/100,000 inhabitants/year. Mean age was 57 +/- 16.8 years and male/female ratio was 2.66/1. The percentage of patients older than 65 years was 33.85%. A history of non-steroidal anti-inflammatory drugs (NSAID) intake within 48 hours before the bleeding episode was obtained in 27.63%. Continued alcohol ingestion was observed in 25.96% and 34.37% of patients gave a history of a previous episode of bleeding. UGH presented with haematemesis and melena in 56% of cases, and 44% only with melena. On admission the bleeding was haemodynamically severe in 12.96% and a 19.69% of the patients had severe associated diseases. Early endoscopy in cases with UGH due to peptic ulcer revealed active bleeding in 16.35% (2.87% in jet and 13.48% oozing) and recent clot/visible vessel in 31.7%. The major causes of bleeding were peptic ulcer (54.31%), esophageal and gastric varices (10.73%) and acute lesions of the gastric mucosa (ALGM) (6.72%). Etiology of the haemorrhage could not be established in 8% of cases. Bleeding was persistent in 20.75% and limited in 79.25% of patients. Emergency surgery was needed in 14.43% of cases. The global mortality of the series was 7.65%.(ABSTRACT TRUNCATED AT 250 WORDS)