Liver depurative techniques: a single liver transplantation center experience.

BACKGROUND: In a liver transplant (LT) center, treatments with Prometheus were evaluated. The main outcome considered was 1 and 6 months survival. METHODS: During the study period, 74 patients underwent treatment with Prometheus; 64 were enrolled, with a mean age of 51 ± 13 years; 47 men underwent 212 treatments (mean, 3.02 per patient). The parameters evaluated were age, sex, laboratorial (liver enzymes, ammonia) and clinical (model for end-stage liver disease and Child-Turcotte-Pugh score) data. RESULTS: Death was verified in 23 patients (35.9%) during the hospitalization period, 20 patients (31.3%) were submitted to liver transplantation, and 21 were discharged. LT was performed in 4 patients with acute liver failure (ALF, 23.7%), in 7 patients with acute on chronic liver failure (AoCLF, 43.7%), and in 6 patients with liver disease after LT (30%). Seven patients who underwent LT died (35%). In the multivariate analysis, older age (P = .015), higher international normalized ratio (INR) (P = .019), and acute liver failure (P = .039) were independently associated with an adverse 1-month clinical outcome. On the other hand, older age (P = .011) and acute kidney injury (P = .031) at presentation were both related to worse 6-month outcome. For patients with ALF and AoCLF we did not observe the same differences. CONCLUSIONS: In this cohort, older age was the most important parameter defining 1- and 6-month survival, although higher INR and presence of ALF were important for 1-month survival and AKI for 6-month survival. No difference was observed between patients who underwent LT or did not have LT.

Infections After Liver Transplantation: A Retrospective, Single-center Study.

OBJECTIVE: To access the incidence of infectious problems after liver transplantation (LT). DESIGN: A retrospective, single-center study. MATERIALS AND METHODS: Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient's variables, graft variables, surgical data, post-LT clinical data. RESULTS: Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 ± 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. CONCLUSION: We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors' variables should be considered in future analyses.

Prophylactic use of liposomal amphotericin B in preventing fungal infections early after liver transplantation: a retrospective, single-center study.

In this study the authors evaluated the efficacy of prophylaxis with liposomal amphotericin B (L-AmB) in the incidence of fungal infections (FI) during the first 3 months after liver transplant (LT). The study was retrospective and accessed a 4-year period from 2008 to 2011. All patients who died in the first 48 hours after LT were excluded. Patients were divided by the risk groups for FI: Group 1, high-risk (at least 1 of the following conditions: urgent LT; serum creatinine >2 mg/dL; early acute kidney injury [AKI] after LT; retransplantation; surgical exploration early post-LT; transfused cellular blood components [>40 U]); and Group 2, low-risk patients. Group 1 patients were further separated into those who received antifungal prophylaxis with L-AmB and those who did not. Prophylaxis with L-AmB consisted of intravenous administration of L-AmB, 100 mg daily for 14 days. Four hundred ninety-two patients underwent LT; 31 died in the first 48 hours after LT. From the remaining 461 patients, 104 presented with high-risk factors for FI (Group 1); of these, 66 patients received antifungal prophylaxis and 38 did not. In this group 8 FI were observed, 5 in patients without antifungal prophylaxis (P = .011). Three more FI were identified in Group 2. By logistic regression analysis, the categorical variable high-risk group was independently related to the occurrence of invasive FI (P = .006). We conclude that prophylaxis with L-AmB after LT was effective in reducing the incidence of FI. No influence on mortality was detected.

Is there a relationship between intraoperative hemodynamic instability and calcineurin inhibitor-related toxicity, early after liver transplantation? A single-center observational study.

This study evaluated the relationship between intraoperative hemodynamic instability (IOHI) and the development of calcineurin inhibitor (CNI) toxicity in the early postoperative period after liver transplantation (LT). Eighty-two patients were enrolled during a 1-year period and a 3-month follow-up. IOHI, requiring continuous infusion of vasopressors, was observed in 31 patients (38%, group 1; control group 2, n = 51). Acute kidney injury (AKI) developed in 28 patients (52% in group 1 vs 24% in group 2, P = .02), and CNI-related neurotoxicity (CNI-NT) in 26 (48% in group 1 vs 22% in group 2, P = .03). Group 1 patients received mainly deceased donor grafts (87% vs 57% in group 2, P < .001). An independent association between IOHI and CNI-NT (P = .029) and AKI (P = .016) was observed. The receiver-operator characteristic curve revealed an area under the curve of 0.63 for IHI (sensitivity 56%; specificity 75%) and 0.65 for AKI (sensitivity 56%; specificity 70.2%). In conclusion, patients undergoing LT with IOHI may be more prone to developing CNI-NT and AKI in the early postoperative period.

Is urinary γ-glutamyl transpeptidase superior to urinary neutrophil gelatinase-associated lipocalin for early prediction of acute kidney injury after liver transplantation?

In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (γ-glutamyl transpeptidase [γGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary γGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary γGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue.

ABO-incompatible liver transplantation in acute liver failure: a single Portuguese center study.

INTRODUCTION: ABO-incompatible liver transplantation (ABOi LT) is considered to be a rescue option in emergency transplantation. Herein, we have reported our experience with ABOi LT including long-term survival and major complications in these situations. PATIENT AND METHODS: ABOi LT was performed in cases of severe hepatic failure with imminent death. The standard immunosuppression consisted of basiliximab, corticosteroids, tacrolimus, and mycophenolate mofetil. Pretransplantation patients with anti-ABO titers above 16 underwent plasmapheresis. If the titer was above 128, intravenous immunoglobulin (IVIG) was added at the end of plasmapheresis. The therapeutic approach was based on the clinical situation, hepatic function, and titer evolution. A rapid increase in titer required five consecutive plasmapheresis sessions followed by administration of IVIG, and at the end of the fifth session, rituximab. RESULTS: From January 2009 to July 2012, 10 patients, including 4 men and 6 women of mean age 47.8 years (range, 29 to 64 years), underwent ABOi LT. At a mean follow-up of 19.6 months (range, 2 days to 39 months), 5 patients are alive including 4 with their original grafts. One patient was retransplanted at 9 months. Major complications were infections, which were responsible for 3 deaths due to multiorgan septic failure (2 during the first month); rejection episodes (4 biopsy-proven of humoral rejections in 3 patients and 1 cellular rejection) and biliary. CONCLUSION: The use of ABOi LT as a life-saving procedure is justifiable in emergencies when no other donor is available. With careful recipient selection close monitoring of hemagglutinins and specific immunosuppression we have obtained acceptable outcomes.

The value of tubular enzymes for early detection of acute kidney injury after liver transplantation: an observational study.

Tubular enzymes (TE) are early markers of acute kidney injury (AKI), but their value for liver transplant (LT) recipients is unknown. We sought to evaluate the usefulness of TE to predict AKI after LT. We enrolled Thirty-nine adult patients without AKI who had been admitted to the Intensive Care Unit (ICU). AKI was diagnosed according to the Acute Kidney Injury Network criteria. Of these patients, 23 had received orthotopic LT and 16 controls had been admitted for other conditions. Urinary lactate dehydrogenase (LDH), alkaline phosphatase (AF) and γ-glutamyl transpeptidase (γ-GT) measured on days 1 and 3 of the ICU stay were normalized to urinary creatinine concentrations. AKI was diagnosed in 14 patients: 8 in the LT group and 6 in the control group. In the LT group, on the first day of the patients' stay in the ICU, urinary LDH (P = .032), AF (P = .022), and γ-GT (P = .002) were significantly higher among those who developed AKI; these elevations preceded those of serum creatinine. In forward receiver-operating characteristic (ROC) plot analysis, the areas under the ROC curves were 0.8, 0.86, and 0.92 for LDH, AF, and γ-GT, respectively. We concluded that TE determined early after LT are a helpful predictors of AKI.

Predictive variables affecting transfusion requirements in orthotopic liver transplantation.

INTRODUCTION AND AIMS: Adult orthotopic liver transplantation (OLT) is associated with considerable blood product requirements. The aim of this study was to assess the ability of preoperative information to predict intraoperative red blood cell (RBC) transfusion requirements among adult liver recipients. METHODS: Preoperative variables with previously demonstrated relationships to intraoperative RBC transfusion were identified from the literature: sex, age, pathology, prothrombin time (PT), factor V, hemoglobin (Hb), and platelet count (plt). These variables were then retrospectively collected from 758 consecutive adult patients undergoing OLT from 1997 to 2007. Relationships between these variables and intraoperative blood transfusion requirements were examined by both univariate analysis and multiple linear regression analysis. RESULTS: Univariate analysis confirmed significant associations between RBC transfusion and PT, factor V, Hb, Plt, pathology, and age (P values all < .001). However, stepwise backward multivariate analysis excluded variables Plt and factor V from the multiple regression linear model. The variables included in the final predictive model were PT, Hb, age, and pathology. Patients suffering from liver carcinoma required more blood products than those suffering from other pathologies. Yet, the overall predictive power of the final model was limited (R(2) = .308; adjusted R(2) = .30). CONCLUSION: Preoperative variables have limited predictive power for intraoperative RBC transfusion requirements even when significant statistical associations exist, identifying only a small portion of the observed total transfusion variability. Preoperative PT, Hb, age, and liver pathology seem to be the most significant predictive factors but other factors like severity of liver disease, surgical technique, medical experience in liver transplantation, and other noncontrollable human variables may play important roles to determine the final transfusion requirements.

Sirolimus: efficacy in liver transplant patients with nephrotoxicity and renal insufficiency.

Nephrotoxicity is a complication of patients undergoing orthotopic liver transplantation. Herein we present several factors that play an important role in this complication.

Haemodynamics during liver transplantation in familial amyloidotic polyneuropathy: study of the intraoperative cardiocirculatory data of 50 patients.

BACKGROUND: Circulatory instability frequently complicates liver transplantation for familial amyloidotic polyneuropathy (FAP) and may be a source of surgical morbidity and mortality. OBJECTIVE: To evaluate FAP intraoperative haemodynamic data and their relation to the duration of surgery, and need for anaesthetic drugs. RBC and sympathomimetic amines. SETTING: Clinical study during a four year period. PATIENTS (mean +/- SD): Group I included 50 consecutive FAP ATTR Met 30 recipients of first transplantation. Age was 35.3 +/- 7.1 years, neurological score 34.3 +/- 13 in 100 and time elapsed from first symptom 5.0 +/- 2.7 years. Group II (control), not different concerning age and sex, included 51 patients transplanted during the same period with other pathologies. METHOD: Anaesthetic protocol, monitoring and surgical techniques were similar in both groups. Data of the two groups were compared either by the Student's t-test or Fisher's exact test. RESULTS: Low values of systemic vascular resistance index were observed in both groups, with no differences between them. Systemic arterial pressures were usually lower in group I, because cardiac index and heart rate were also significantly lower, although within normal values. However, in group I, isoflurane (a vasodilator anaesthetic) was used during less time (p < 0.05) and in lower concentrations (p < 0.01) and phenylephrine was necessary in 26% of patients vs 0 patients in group II (p < 0.001). CONCLUSION: FAP patients presented a different intraoperative behaviour when compared to other patients submitted to liver transplantation. From a clinical point of view, the authors stress: 1--As a result of autonomic dysfunction, the administration of anaesthetic drugs to FAP patients always presents the risk of producing significant hypotension; even the use of ketamine does not prevent hypotension; 2--Safety is ensured by beat-to-beat surveillance of arterial pressures and the capacity to act immediately to support circulation; 3--These patients seem to be very sensitive to decreases in the pre-load; 4--Hypotension is also frequent with an adequate pre-load, usually as the result of low SVR; an infusion of a vasoconstrictor drug emerges as the most frequent treatment requested and our experience supports it as an effective one.

Liver transplantation for familial amyloid polyneuropathy.

Familiar Amyloid Polyneuropathy (FAP), an autosomal dominant inherited multisystemic disorder was first observed by Corino de Andrade, a Portuguese neurologist, in 1939. This disease of Portuguese origin was probably spread by fishermen, mainly to Sweden and Japan. It is characterized by a progressive peripheral polyneuropathy and autonomic neuropathy (erectile sexual disfunction, gastrointestinal disfunction, bladder dysfunction and cardio vascular disease) and malnutrition. There are neural and systemic amiloid deposits. Type I FAP, of Portuguese origin, is the most common variety. The amyloid protein is the variant transthyretin (TTR) in which methionine (MET) is a substitute for valine in position 30 (TTR MET 30). It is mainly produced by the liver (90%) and, in small amounts, by the choroidal plexus. Symptoms usually start in the 3rd and 4th decade of life and the patients usually die within 10-15 years. From the therapeutic options--plasmapheresis, immunoadsorption and liver transplantation; the latter seems to be the only one, which stops the production of TTR MET 30 in a permanent way, by means of the liver. The lack of any other effective therapy and the success of the first liver transplantation performed in Sweden arouse great hope. So far, around 300 patients have been transplanted all over the world. A hundred and thirty of them were transplanted in Portugal. A Kaplan Meier survival curve of the Portuguese patients shows a survival rate of 78% at 5 years. However, in spite of the progression of the disease being halted, the irreversibility of some neurological lesions seems to persist. This fact raises the problem of the timing of the transplantation. It seems that the patients should be transplanted as soon as the symptoms start, since mortality and severe morbidity seems to mainly involve those in whom symptomatic disease has lasted longer than six years. As the explanted liver is a morphologic normal liver, a sequential (domino) transplant has been carried out in 16 cases so far done--by one of the authors (ALF) on patients with either hepatocellular carcinoma or liver metastatic disease.

Serum potassium concentrations after suxamethonium in patients with familial amyloid polyneuropathy type I.

BACKGROUND: Suxamethonium produces an abnormal increase in serum potassium in some neurological diseases and some authors have suggested that it is safer not to use this drug in patients with familial amyloid polyneuropathy (FAP). However, there are no data previously reported to support this hypothesis. The aim of this study was to evaluate the magnitude of the potassium increase produced by suxamethonium in FAP type I. METHOD: Twenty-one FAP Met 30 patients anaesthetised for liver transplantation were studied. Age was 34.9 +/- 6.9 years (mean +/- SD), time elapsed from first symptom 5.5 +/- 3.2 years and weight was 14 +/- 9% below ideal body weight. Anaesthesia was induced with thiopentone and low-dose fentanyl. Samples for blood gas and 5 min after 1 mg/kg of suxamethonium was given for tracheal intubation. RESULTS: Before induction serum potassium levels were 3.8 +/- 0.4 mmol/L. One minute after suxamethonium, values were 3.8 +/- 0.4 mmol/L and 5 min after 4.3 +/- 0.5 mmol/L. The maximal increase observed was 1.6 mmol/L (from 3.4 mmol/L to 5.0 mmol/L). CONCLUSION: The average increase in plasma potassium concentrations observed in FAP patients after suxamethonium was similar to the increase observed in a normal population by others. Our study can exclude the hypothesis that an anomalous increase in potassium would be a typical and frequent response to suxamethonium in FAP met 30 patients. However, we cannot exclude that a dangerous rise in serum potassium may exist in a certain percentage of FAP patients.