Elective Liver Transplantation Research Articles

Domino Liver Transplantation in Maple Syrup Urine Disease: A Case Report and Review of the Literature

BackgroundImproved outcomes have expanded the indications for liver transplantation, thus aggravating the already limited supply of donor organs. Domino liver transplantation (DLT) has been one strategy to augment the supply of donor organs in cases of inborn errors of metabolism. One such disease is maple syrup urine disease (MSUD), an inherited disorder of branched-chain amino acid (BCAA) metabolism. MethodsWe report on the transplantation of a deceased donor liver into a patient with MSUD, and the sequential transplantation of the explanted liver into a patient with hemophilia A, HIV, hepatitis C, and a low priority on the transplant waiting list. ResultsAt 30 months, the MSUD recipient has had significant correction of BCAA metabolism on a protein-unrestricted diet and no progression of neuropsychiatric symptoms. The DLT recipient has been cured of hemophilia and has normal BCAA homeostasis. This case provides further evidence that elective orthotopic liver transplantation for MSUD attenuates the disease with restoration of BCAA metabolism, and that DLT in this setting can achieve excellent results in ESLD patients. ConclusionIt is possible that domino grafts from patients with MSUD could be used in more conventional recipients, but additional studies and longer-term outcomes are needed to determine the validity of DLT in MSUD.

Bloodstream Infection After Elective Liver Transplantation Is Associated With Increased Mortality in Patients With Cirrhosis

Purpose This study aims to investigate what factors predict the development of postoperative bloodstream infection (BSI) in patients transplanted electively for chronic liver disease and compare outcomes in infected transplant recipients (BCLD) with noninfected patients (CLD). Methods A retrospective cohort study of 218 patients who had elective liver transplantation (LT) between January 2003 and July 2005 and admitted to a specialist intensive care unit (ICU) was done. Results Fifteen patients had BSI post-LT (BCLD, 29 isolates) while in the ICU, and 203 patients did not (CLD). Thirty-eight percent of isolates were gram negatives; 55%, gram positives; and 7%, fungemia. Median time to first BSI post-LT was 11 days (range, 3-16 days). On admission post-LT to the ICU, patients with BCLD had higher Acute Physiology and Chronic Health Evaluation II scores (23 vs 10, P < .001). While in the ICU, patients with BCLD had greater requirements for renal replacement therapy (73% vs 8%) and days on mechanical ventilation (17 vs 2 days) and longer median ICU stay (21 vs 3 days, P < .001 for all). One-year survival was worse in the BCLD group (40% vs 94%, P < .001). On multivariate analysis, Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.36) post-LT was independently associated with subsequent BSI. Bloodstream infection (hazards ratio, 8.7) was independently associated with mortality. Conclusion Bloodstream infection post-LT was associated with increased severity of illness on admission, greater requirements for organ support, and increased mortality.

PTU-067 Out-patient assessment for liver transplantation: a single centre experience

IntroductionAssessment for orthotopic liver transplantation (LT) traditionally requires admission to hospital. In 2010, the liver unit at the University Hospital Birmingham (UHB) launched the first UK-based out-patient assessment programme (OPA)....

Modifiable patient factors are associated with the late decline in renal function following liver transplantation

Strategies to delay or avoid the long-term decline in renal function and progression to chronic kidney disease (CKD) in liver transplant recipients remain unclear. Our aim was to examine the change in estimated GFR (eGFR) from six months after liver transplantation, and to identify modifiable factors associated with a faster rate of decline. This was a single-center retrospective study of 97 patients who underwent elective liver transplantation and survived ≥ 5 yr. eGFR was estimated using the MDRD6-variable equation, and the annualized change in eGFR was determined using simple linear regression. The baseline eGFR was 75 mL/min/1.73 m(2) . Thereafter, eGFR declined at a mean rate of 1.08 mL/min/1.73 m(2) per year. 49% had a decline in renal function greater than the rate expected with aging. Decline in eGFR was an independent predictor of CKD by five yr post-transplant (p = 0.001). Multivariate modeling found a higher baseline eGFR (p < 0.001), female gender (p = 0.006), hypertension (p = 0.019), and dyslipidemia (p = 0.034) to be associated with a faster rate of decline in renal function. In conclusion, liver transplant recipients have a clinically relevant decline in eGFR from six months post-transplant. Prospective studies are required to examine the effects of aggressive blood pressure and lipid control on the development of CKD in this setting.

Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation.

Liver transplantation has a significant early postoperative mortality rate. An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources. This study assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing (CPET) for determining the cardiopulmonary reserve in patients being assessed for liver transplantation and its potential for predicting 90-day posttransplant survival. One hundred eighty-two patients underwent CPET as part of their preoperative assessment for elective liver transplantation. The 90-day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow-up. One hundred sixty-five of the 182 patients (91%) successfully completed CPET; this was defined as the ability to determine a submaximal exercise parameter: the anaerobic threshold (AT). Sixty of the 182 patients (33%) underwent liver transplantation, and the mortality rate was 10.0% (6/60). The mean AT value was significantly higher for survivors versus nonsurvivors (12.0 ± 2.4 versus 8.4 ± 1.3 mL/minute/kg, P < 0.001). Logistic regression revealed that AT, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes. In a multivariate analysis, only AT was retained as a significant predictor of mortality. A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 90.7% and 83.3%, respectively, with good model accuracy (area under the receiver operating characteristic curve = 0.92, 95% confidence interval = 0.82-0.97, P = 0.001). The optimal AT level for survival was defined to be >9.0 mL/minute/kg. The predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age. In conclusion, the preoperative cardiorespiratory reserve (as defined by CPET) is a sensitive and specific predictor of early survival after liver transplantation. The predictive value of CPET requires further evaluation.

Intraoperative, rapid administration of high-dose fentanyl by a dysfunctioning plunger lock of a syringe pump; the siphon effect

Syringe pumps are designed to deliver drugs in a safe manner, however, these devices can be potentially dangerous if operated improperly. A 50-year-old male was scheduled to undergo an elective liver transplantation. After induction of anesthesia, the Baxter AS40A pump was loaded with a 50 ml Becton Dickinson syringe containing 2,500 µg of fentanyl. Continuous infusion at 5 ml/hr was started without knowing that part of the plunger lock, i.e. the upper plunger clamp assembly, was damaged (Fig. 1), and, therefore, the plunger was incompletely clamped without notice. Ten minutes later the patient experienced marked sinus bradycardia and hypotension for which a rescue drug of 10 µg of epinephrine was injected twice. Surprisingly, the syringe loaded on AS40A was found to be empty and the missing 50 ml of fentanyl was concluded to have been infused rapidly into the patient. However, even at this point there was no alarm signal or error message to indicate a dysfunctional plunger clamp. Fig. 1 A Baxter AS40A pump with a normal (A) and damaged (B) plunger clamp assembly which dose not firmly hold the plunger. Of many possible reasons, a siphon effect was strongly suspected to be the cause of this mishap, which refers to the continuous flow of liquids through enclosed conduit by the force of gravity once it had been initiated, because we can acknowledge that a complete spillage of 50 ml syringe volume occurred within five minutes when the plunger lock was unclamped and manually started. Although high-dose fentanyl administration has been seen to be hemodynamically stable [1], such as in this case, bolus administration of another drug such as dopamine or norepinephrine, which is usually delivered using a Baxter infusion pump, may have catastrophic effects. Although a newer version of the Baxter AS40A pump has an alarm sensor for the syringe plunger lock, understanding the specifics of commonly used, older equipment in the operating room is crucial [2], and meticulous attention to a possibly improperly secured plunger head is always warranted in order to avoid potentially adverse outcomes.

Emergency versus elective living-donor liver transplantation: a comparison of a single center analysis

PurposeWe studied the risk factors for postoperative mortality between patients who underwent emergency or elective living-donor liver transplantation (LDLT).MethodsForty-seven patients underwent LDLT in our institute, 16 for emergencies and 31 as elective procedures. The emergency LDLT status was applied to cases in which the time period between referral to our institution and transplantation did not exceed 10 days, and in which liver failure was accompanied by the presence of any degree of hepatic encephalopathy.ResultsWith regard to preoperative factors, age (P = 0.03), the model for end-stage liver disease score (P = 0.001), preoperative tracheal intubation (P = 0.001), ratio between arterial oxygen tension and fractional inspired oxygen (PaO2/FiO2 ratio) (P = 0.03), steroid therapy use (P = 0.001), lymphocyte count (P = 0.02), and cases requiring hemodiafiltration (P = 0.001) differed significantly between the two groups. Postoperative pneumonia occurred more frequently in emergency LDLT patients than in elective LDLT patients (P = 0.006). Invasive pulmonary aspergillosis (IPA) was the main cause of postoperative death in emergency LDLT patients, and, in a univariate analysis, a preoperative status of high serum (1 → 3)-β-d-glucan (>20 pg/ml, P = 0.001), advanced age (>52 years, P = 0.02), and a low PaO2/FiO2 ratio (<320, P = 0.01) were identified as factors predictive of IPA.ConclusionCareful perioperative management, including preoperative investigation of aspergillosis and empiric antibiotic therapy, should be considered for emergency LDLT patients who fulfill IPA risk factors.

Elective Liver Transplant List Mortality: Development of a United Kingdom End-Stage Liver Disease Score

Prediction of short-term survival probability is important in the selection and allocation of patients for liver transplantation, and the Mayo End-Stage Liver Disease (MELD) score has been used in these contexts. The aim of this study was to develop and validate a model for estimation of short-term prognosis of patients selected for elective liver transplantation in the United Kingdom. A modeling dataset was based on 1103 adult patients registered for a first elective liver transplant in the United Kingdom between April 1, 2003, and March 31, 2006, and a validation dataset based on 452 patients registered between April 1, 2006, and March 31, 2007. The final model (United Kingdom End-Stage Liver Disease) included international normalized ratio, serum creatinine, bilirubin, and sodium. The model, based on the modeling dataset, accurately predicted mortality on the transplant list in the validation dataset and proved to be a better predictor than MELD or MELD-Na. The United Kingdom End-Stage Liver Disease score was not associated with overall posttransplant survival but was associated with both the duration of intensive care unit stay and overall initial hospital stay. This model, developed specifically for patients awaiting liver transplantation, provides a useful tool for the selection of patients for liver transplantation and the allocation of donor livers.

Liver transplantation for propionic acidemia in children

Propionic acidemia (PA) is a rare inherited disorder of branched chain amino acid metabolism; despite improvements in conventional medical management, the long-term outcome remains disappointing. Liver transplantation (LT) has been proposed to minimize the risk of further metabolic decompensations and to improve the quality of life. We performed a retrospective review of all children with PA who underwent LT between 1987 and 2008. Five children were identified with a median age of 1.2 years (range = 0.7-4.1 years) at referral. Four of the children presented clinically at 3 weeks of age or less, and 1 child was diagnosed prenatally. All had metabolic acidosis and hyperammonemia. Two had seizures and required intensive care; this care included inotropic support and continuous venovenous hemofiltration in 1 child. The children were considered for elective LT for the following reasons: frequent metabolic decompensations (2), previous sibling death (2), and elective management (1). One child underwent auxiliary LT, and 4 children received orthotopic grafts (1 living related graft). The median age at LT was 1.5 years (range = 0.8-7.0 years). There was 1 retransplant 3 months after LT due to hepatic artery thrombosis. One year after LT, 1 patient suffered a metabolic stroke with minimal residual neurology. After a median follow-up of 7.3 years (range = 2.2-15.0 years), all the children had normal graft function and a good quality of life with a protein-unrestricted diet and no further metabolic decompensations. In conclusion, LT has a role in the management of PA: it reduces the risk of metabolic decompensation and improves the quality of life. The potential for the development of metabolic sequelae is not completely eliminated.

Bloodstream infection after elective liver transplantation is associated with increased mortality in patients with cirrhosis

PurposeThis study aims to investigate what factors predict the development of postoperative bloodstream infection (BSI) in patients transplanted electively for chronic liver disease and compare outcomes in infected transplant recipients (BCLD) with noninfected patients (CLD). MethodsA retrospective cohort study of 218 patients who had elective liver transplantation (LT) between January 2003 and July 2005 and admitted to a specialist intensive care unit (ICU) was done. ResultsFifteen patients had BSI post-LT (BCLD, 29 isolates) while in the ICU, and 203 patients did not (CLD). Thirty-eight percent of isolates were gram negatives; 55%, gram positives; and 7%, fungemia. Median time to first BSI post-LT was 11 days (range, 3-16 days). On admission post-LT to the ICU, patients with BCLD had higher Acute Physiology and Chronic Health Evaluation II scores (23 vs 10, P < .001). While in the ICU, patients with BCLD had greater requirements for renal replacement therapy (73% vs 8%) and days on mechanical ventilation (17 vs 2 days) and longer median ICU stay (21 vs 3 days, P < .001 for all). One-year survival was worse in the BCLD group (40% vs 94%, P < .001). On multivariate analysis, Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.36) post-LT was independently associated with subsequent BSI. Bloodstream infection (hazards ratio, 8.7) was independently associated with mortality. ConclusionBloodstream infection post-LT was associated with increased severity of illness on admission, greater requirements for organ support, and increased mortality.

Domino versus deceased donor liver transplantation: Association with early graft function and perioperative bleeding

This study sought to evaluate the potential impact of domino liver transplantation (DLT) on initial graft function and early postoperative outcome in patients with cirrhosis in a Portuguese liver transplantation center. A retrospective comparative analysis was performed between 77 domino recipients (from familial amyloidotic polyneuropathy donors) and 91 deceased donor recipients, all submitted to primary elective whole liver transplantation, using the piggyback technique, in a 42-month period. Outcome parameters included graft dysfunction (defined as either primary nonfunction or initial poor function, according to the Ploeg-Maring criteria) and Clavien II-IV complications in the first postoperative week. Domino and deceased donor recipients had similar preoperative severity indices (Child-Pugh classification and Model for End-Stage Liver Disease score) and immediate postoperative severity scores (APACHE II [Acute Physiology and Chronic Health Evaluation II] and SAPS II [Simplified Acute Physiology Score II]). In DLT, donors were younger, cold ischemia time was shorter, and intraoperative transfusion requirements of packed red blood cells and fresh-frozen plasma were significantly lower. Graft dysfunction incidence was 3.4-fold lower in DLT: 5.2% (only 4 cases of initial poor function) versus 18.0% (1 primary nonfunction and 15 cases of initial poor function), P = 0.010. Postoperative bleeding was the most frequent early Clavien II-IV complication (n = 29, 17.3%), with an incidence 2.2-fold lower in domino recipients. A statistically significant difference was not found in the other analyzed Clavien II-IV complications, intensive care unit stay, mechanical ventilation time, intensive care unit mortality, and 1-year survival rate. In conclusion, in this study the younger donors and shorter ischemic time associated with DLT may provide a protective role in regards to graft dysfunction and perioperative bleeding, which are 2 important determinants of early morbidity after liver transplantation.

P99 Relation of donor risk index and model for end-stage liver disease score to outcome of elective liver transplantation; a single centre experience

IntroductionPatients with advanced liver disease, reflected in high model for end-stage liver disease (MELD) scores have the lowest chances of survival without liver transplantation (LT) and yet, may derive greatest...

P103 Clinical utility of myocardial perfusion imaging in liver transplant assessment patients

IntroductionCoronary artery disease (CAD) is associated with increased short-term morbidity and mortality following liver transplantation. As a result, the AASLD recommends that high risk individuals should undergo CAD evaluation during...

P92 Predictive factors for early cardiac events following liver transplantation

IntroductionCoronary artery disease (CAD) is associated with increased short-term morbidity and mortality following liver transplantation. As a result, the AASLD recommends that all high risk individuals should undergo CAD evaluation...

Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study

Background Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT). Methods Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy ( Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group. Results Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp ( P = .033 vs BLO group). No other type of complication showed any difference between the groups. Conclusions Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.

Medical and psychiatric outcomes for patients transplanted for acetaminophen-induced acute liver failure: a case-control study

Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure (ALF) in the UK. Patients often consume the drug with suicidal intent or with a background of substance dependence. We compared the severity of pretransplant illness, psychiatric co-morbidity, medical and psychosocial outcomes of all patients who had undergone liver transplantation (LT) emergently between 1999-2004 for acetaminophen-induced ALF (n=36) with age- and sex-matched patients undergoing emergent LT for non-acetaminophen-induced ALF (n=35) and elective LT for chronic liver disease (CLD, n=34). Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0/35, CLD=2/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT). Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance.

Antimicrobial prophylaxis in liver transplant patients – a multicenter survey endorsed by the European Liver and Intestine Transplant Association

Perioperative infections remain an important problem for patients undergoing liver transplantation (LT). For prevention of these infections, perioperative prophylaxis has become the standard procedure. Yet, either guidelines or data on current practice are lacking. The aim of the study was to gain insight into prophylactic antimicrobial strategies used in Europe. A survey questionnaire was sent out to all LT centers that are member of the European Liver and Intestine Transplant Association. In the survey questionnaire, we asked for details on the prophylactic antimicrobial regimen used in LT recipients. The response rate was 48%. Antibiotic prophylaxis for elective LT was provided by a first-line betalactam antibiotic or co-trimoxazole in 25%. Seventy-three per cent of those centers surveyed gave an extended spectrum, and one center used a 6-month rotation strategy. Antifungal prophylaxis was administered in 35% of centers in all LT recipients, in 53% of centers in patients at risk, and in 12% of centers not at all. Cytomegalovirus prophylaxis was never administered in 10%. In 12% of the centers surveyed, all the patients received cytomegalovirus prophylaxis, and another 78% of the centers gave it only to risk groups. In Europe, there is a considerable variation in the different antibiotic, antifungal and cytomegalovirus prophylactic strategies used for LT. These findings underscore the need for randomized controlled trials to determine the optimal prophylactic antimicrobial regimen.

Safe use of segmental liver grafts from donors after cardiac death (DCD) in children with acute liver failure

Emergency liver transplantation is a life-saving procedure in selected subset of children with acute liver failure (ALF), when most recipients receive a segmental graft from a living or heart-beating deceased donor. The increased use of full-liver grafts from donors after cardiac death (DCD) has had a beneficial impact on elective liver transplantation in adults. These grafts however are more susceptible to poor initial function, and most centres are reluctant to consider their use as segmental grafts, let alone in the situation of ALF where good initial function is imperative. In this short article, we describe the use and successful outcome in two children aged 6 weeks and 6 years with acute liver failure who received reduced-size DCD liver grafts.

Predicting outcome in patients with cirrhosis following acute decompensation: Can we do better?

Predicting outcome in patients with cirrhosis following acute decompensation: Can we do better?

Smoking-related morbidity and mortality following liver transplantation

Smoking is the world's leading cause of premature mortality responsible for an estimated 5 million deaths each year. Although the negative health implications of cigarette smoking in the nontransplant setting are well recognized, the effect on patient and graft survival post liver transplantation remains unclear. The aim of this study was therefore to assess the influence of smoking on morbidity and mortality following liver transplantation. We performed a retrospective single-center case-note study of 136 consecutive patients who underwent elective liver transplantation between January 1, 1996 and December 31, 2000. Patients were defined as active smokers (23%), exsmokers (18%), or life-long nonsmokers (58%) on the basis of documentation at the time of transplant assessment. Active smoking was associated with increased all-cause mortality post transplant, with estimated 1-, 5-, and 10-year survival of 94%, 68%, and 54%, respectively, versus 94%, 83%, and 77% for nonsmokers (P = 0.04). A multivariate Cox proportional hazards model identified smoking as an independent predictor of death (hazard ratio 2.23, 95% confidence interval 1.08-4.61, P = 0.03). Active smokers demonstrated increased cardiovascular-specific mortality (P = 0.01) and sepsis-specific mortality (P = 0.02) but not malignancy-related mortality (P = 0.61) and had graft survival similar to that of nonsmokers (P = 0.88). Exsmokers did not have an increased risk of death (P = 0.134). In conclusion, active smokers at time of assessment have increased mortality post liver transplantation, which is non-graft-related and appears to be a result of increased cardiovascular-related and sepsis-related death. Prospective studies are required to assess the impact of smoking cessation on long-term outcome.