Perioperative fatal pulmonary embolism in a pediatric liver transplant recipient.

Patients with cirrhotic liver disease are in a state of fluctuating hemostatic balance. Hepatic synthetic dysfunction is commonly complicated by coagulation disorders that constitute an important parameter of most prognostic scores. The dominant feature of this dysfunction is bleeding tendencies, but cirrhotic patients may also exhibit inappropriate clotting and pro-coagulation placing them at risk for thromboembolism. We present a case of perioperative fatal pulmonary embolism in an 8-year-old patient with biliary cirrhosis secondary to drug-induced vanishing bile duct syndrome undergoing a deceased donor liver transplant. The massive pulmonary embolism occurred intra-operatively after reperfusion of the donor liver. Despite the initiation of extracorporeal membrane oxygenation, the postoperative course was complicated by bleeding and the patient expired. This unique case highlights the need for venous thromboembolism prevention by screening and prophylaxis prior to liver transplant in at least a subpopulation of pediatric patients. While the risk of thrombosis postoperatively in pediatrics patients is well known, the preoperative risk is less frequently described and deserves attention and practice changing action.

Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease.

AIM: To evaluate risk of recidivism on a case-by-case basis. METHODS: From our center's liver transplant program, we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium (OSOTC) exception criteria. They were considered to have either a low or medium risk of recidivism, and had at least one or three or more months of abstinence, respectively. They were matched based on gender, age, and Model for End-Stage Liver Disease (MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data. RESULTS: Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls. Nineteen patients (53%) with a median [Inter-quartile range (IQR)] MELD score of 24 (13) received transplant and were followed for a median of 3.4 years. They were matched to 38 controls with a median (IQR) MELD score of 25 (9). At one and five years, cumulative survival rates (± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls, respectively (Log-rank test, P = 0.837). Four (21%) patients resumed drinking by last follow-up visit. CONCLUSION: Compared to traditional criteria for assessment of risk of recidivism, a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation.

Split liver transplantation in adults.

Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

Role of donor hemodynamic trajectory in determining graft survival in liver transplantation from donation after circulatory death donors.

Donation after circulatory death (DCD) donors show heterogeneous hemodynamic trajectories following withdrawal of life support. Impact of hemodynamics in DCD liver transplant is unclear, and objective measures of graft viability would ease transplant surgeon decision making and inform safe expansion of the donor organ pool. This retrospective study tested whether hemodynamic trajectories were associated with transplant outcomes in DCD liver transplantation (n = 87). Using longitudinal clustering statistical techniques, we phenotyped DCD donors based on hemodynamic trajectory for both mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2 ) following withdrawal of life support. Donors were categorized into 3 clusters: those who gradually decline after withdrawal of life support (cluster 1), those who maintain stable hemodynamics followed by rapid decline (cluster 2), and those who decline rapidly (cluster 3). Clustering outputs were used to compare characteristics and transplant outcomes. Cox proportional hazards modeling revealed hepatocellular carcinoma (hazard ratio [HR] = 2.53; P = 0.047), cold ischemia time (HR = 1.50 per hour; P = 0.027), and MAP cluster 1 were associated with increased risk of graft loss (HR = 3.13; P = 0.021), but not SpO2 cluster (P = 0.172) or donor warm ischemia time (DWIT; P = 0.154). Despite longer DWIT, MAP and SpO2 clusters 2 showed similar graft survival to MAP and SpO2 clusters 3, respectively. In conclusion, despite heterogeneity in hemodynamic trajectories, DCD donors can be categorized into 3 clinically meaningful subgroups that help predict graft prognosis. Further studies should confirm the utility of liver grafts from cluster 2. Liver Transplantation 22 1469-1481 2016 AASLD.

Risk stratification of allograft failure secondary to hepatitis C recurrence after liver transplantation.

AIM: Hepatitis C virus (HCV) recurrence after liver transplantation decreases survival rates. Improved understanding of the multiple factors influencing HCV recurrence could aid decision-making for donor-recipient pairing and maximize transplant outcomes. The aim of this study was to create a model based on pretransplant variables to stratify patients at risk of HCV-related allograft failure. METHODS: This retrospective study enrolled 154 liver transplant recipients with HCV at Cleveland Clinic. RESULTS: Among the study population, 54 recipients (35.1%) experienced HCV recurrence, histologically defined as moderate to severe hepatitis and/or bridging fibrosis to cirrhosis. The multivariate analysis found donor age (≥60 years, P < 0.002), donor body mass index (≥30 kg/m2 , P < 0.05), African American recipient (P < 0.01) and genotype 1 (P < 0.02) as risk factors for HCV-related allograft failure. When these four factors were scored as a combined index (no factor [n = 15], one factor [n = 76], two factors [n = 43] and three or more factors [n = 20]), the HCV recurrence-free survival showed good stratification according to the scores: 93.3% with no factor, 79.3% with one factor, 52.0% with two factors and 24.4% with three or more factors at 3 years after transplant (P < 0.0001). Moreover, this risk index also identified the patient group at high risk of HCV recurrence after acute rejection. CONCLUSION: While the introduction of direct-acting antiviral agents has been changing the paradigm of HCV treatment, the natural history of recipients with HCV as shown in this study would help estimate the risk of HCV-related allograft failure in those who do not tolerate such new treatment.

Liver transplantation for nonalcoholic steatohepatitis in young patients.

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of obesity and insulin resistance. The aim of this study was to determine the frequency of NASH as an indication for liver transplantation (LT) in children and young adults and to characterize patient and graft survival. The study included all children and young adult patients (up to the age of 40 years) who underwent LT in the United States for NASH cirrhosis from the 1987 to 2012 United Network for Organ Sharing (UNOS) database. Kaplan-Meier analysis was used to assess patient and graft survival. A total of 330 patients were included, 68% were Caucasian, and the mean BMI was 33.6 ± 6.3. Age at time of LT ranged between 4 and 40 years (mean 33.9 ± 6.6 years). Fourteen subjects were <18 years of age at time of LT and 20 were between the ages of 18 and 25 years. Median follow-up after 1st LT was 45.8 months [10.7, 97.3]. During this time, 30% of subjects (n = 100) died and 11.5% (n = 38) were retransplanted including 13 for NASH recurrence. In conclusion, NASH can progress to end-stage liver disease requiring LT in childhood and early adulthood. A significant number of young patients transplanted for NASH cirrhosis required retransplantation.

Impact of donor age in liver transplantation from donation after circulatory death donors: A decade of experience at Cleveland Clinic.

The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation.

A Structured Educational Curriculum Including Online Training Positively Impacts American Board of Surgery In-Training Examination Scores.

OBJECTIVE: To assess the effect of a structured postgraduate year 1 educational curriculum, including online surgical training, on American Board of Surgery In-Training Examination (ABSITE) scores. DESIGN: This was a retrospective cohort study. SETTING: The study was performed in an academic surgical residency program in a tertiary care hospital, Cleveland Clinic Foundation, Cleveland, Ohio. PARTICIPANTS: The participants were 140 surgical postgraduate year 1 residents from 2000 to 2009. Interns from 2000 to 2004 were grouped together and completed a self-directed learning curriculum. Interns from 2005 to 2009 participated in a structured educational curriculum that included lectures and the use of an online program. Lectures were based on the American College of Surgeons curriculum. The online program consisted of 8 to 12 hours of assigned tutorials and quizzes that corresponded to the lectures and 3 multiple-choice (MC) examinations. RESULTS: Use of a structured educational curriculum led to improved ABSITE scores (66 ± 9%) compared with that of those who had no curriculum (55 ± 10%, p < 0.001). Several variables positively correlated with the ABSITE score: United States Medical Licensing Examination step 1 score (p < 0.001), monthly quiz scores (p = 0.003), average MC examination scores (p = 0.005), lecture attendance (p = 0.02), and time spent online (p = 0.04). Multivariable analysis demonstrated that the step 1 United States Medical Licensing Examination score, time spent online, and MC examination score are predictive of total the ABSITE score. When ABSITE subscores (basic science and clinical science) were compared, the online curriculum had a greater effect on basic science subscores, whereas lectures had a greater effect on clinical science subscores. CONCLUSIONS: Providing surgery residents a structured curriculum with lectures and an online component positively impacts ABSITE scores.

Safety and efficacy of splenic artery embolization for portal hyperperfusion in liver transplant recipients: a 5-year experience.

Severe portal hyperperfusion (PHP) after liver transplantation has been shown to cause intrahepatic arterial vasoconstriction secondary to increased adenosine washout (hepatic artery buffer response). Clinically, posttransplant PHP can cause severe cases of refractory ascites and hydrothorax. In the past, we reported our preliminary experience with the use of splenic artery embolization (SAE) as a way to reduce PHP. Here we present our 5-year experience with SAE in orthotopic liver transplantation (OLT). Between January 2007 and December 2011, 681 patients underwent OLT at our institution, and 54 of these patients underwent SAE for increased hepatic arterial resistance and PHP (n=42) or refractory ascites/hepatic hydrothorax (n=12). Patients undergoing SAE were compared to a control group matched by year of embolization, calculated Model for End-Stage Liver Disease score, and liver weight. SAE resulted in improvements in hepatic artery resistive indices (0.92±0.14 and 0.76±0.10 before and after SAE, respectively; P<0.001) and improved hepatic arterial blood flow (HAF; 15.6±9.69 and 28.7±14.83, respectively; P<0.001). Calculated splenic volumes and spleen/liver volume ratios were correlated with patients requiring SAE versus matched controls (P=0.002 and P=0.001, respectively). Among the 54 patients undergoing SAE, there was 1 case of postsplenectomy syndrome. No abscesses, significant infections, or bleeding was noted. We thus conclude that SAE is a safe and effective technique able to improve HAF parameters in patients with elevated portal venous flow and its sequelae.

Safety and effectiveness of renoportal bypass in patients with complete portal vein thrombosis: an analysis of 10 patients.

The presence of portal vein thrombosis (PVT) is still considered by many transplantation centers to be an absolute contraindication to liver transplantation because of the technical difficulties that it can present and its association with a higher rate of patient morbidity and mortality. Renoportal bypass (RPB) can help to remove these barriers. This study describes our institution's experience with RPB through the description of a new and successful simplified surgical strategy, a patient and graft outcome analysis, intraoperative vascular flow measurements, and the use of splenic artery embolization (SAE) as an effective adjunct for treating sporadic cases of unrelieved portal hypertension. Between January 2004 and January 2013, 10 patients with grade 4 PVT underwent RPB. At the last follow-up (42.2 ± 21.1 months), the patient and graft survival rates were 100%. Five patients (50%) experienced posttransplant ascites, and 2 of those underwent proximal SAE to modulate the liver inflow and overcome the ascites. Three patients (30%) experienced transient kidney injury in the early posttransplant period and were treated efficiently with medical therapy. The renoportal flows were close to the desirable 100 mL/100 g of liver tissue in all cases. The experience and data support RPB as a feasible and easily reproducible technique without the risks and technical challenges associated with the tedious dissection of a cavernous hilum.

Predictors of poor outcome among older liver transplant recipients.

With the increasing age of recipients undergoing orthotopic liver transplant (OLT), there is need for better risk stratification among them. Our study aims to identify predictors of poor outcome among OLT recipients ≥ 60 yr of age. All patients who underwent OLT at Cleveland Clinic from January 2004 to April 2010 were included. Baseline patient characteristics and post-OLT outcomes (mortality, graft failure, length of stay, and major post-OLT cardiovascular events) were obtained from prospectively collected institutional registry. Among patients ≥ 60 yr of age, multivariate regression modeling was performed to identify independent predictors of poor outcome. Of the 738 patients included, 223 (30.2%) were ≥ 60 yr. Hepatic encephalopathy, platelet counts < 45,000/µL, total serum bilirubin > 3.5 mg/dL, and serum albumin < 2.65 mg/dL independently predicted poor short-term outcomes. The presence of pre-OLT coronary artery disease and arrhythmia were independent predictors of poor long-term outcomes. Cardiac causes represented the second most common cause of mortality among the elderly cohort. Despite that, this carefully selected cohort of older OLT recipients had outcomes that were comparable with the younger recipients. Thus, our results show the need for better pre-OLT evaluation and optimization, and for closer post-OLT surveillance, of cardiovascular disease among the elderly.

Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model.

INTRODUCTION: Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers. MATERIALS AND METHODS: After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology. RESULTS: No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury. CONCLUSION: Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.

Oxygen consumption predicts outcome in porcine partial liver grafts.

BACKGROUND: High oxygen consumption (OC) in recipients of cadaveric whole liver grafts is associated with a poor prognosis. The aim of this study is to investigate the relationship between intraoperative hepatic OC and graft function and survival in a porcine partial liver graft model. MATERIAL AND METHODS: Experiments followed the Guiding Principles in the Care and Use of Laboratory Animals. Fourteen female pigs, 46-69 kg, received liver allografts of 17%-39% liver volume and were followed for 14 d. We measured donor and recipient body weights, percentage graft weight and expressed it as a percentage of standard liver volume, cold ischemia time, hepatic artery flow (HAF), portal vein flow (PVF), graft volume at sacrifice, serum lactate, prothrombin time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, albumin, total protein, alkaline phosphatase, total bilirubin, and recipient survival. OC was calculated as follows: OC (mL/100 g/min) = ([Hemoglobin {Hb} × 1.34 × SaO2 + 0.003 × PaO2] × HAF + [Hb × 1.34 × SpO2 + 0.003 × PpO2] × PVF - [Hb × 1.34 × SvO2 + 0.003 × PvO2] × [HAF + PVF])/graft weight (100 g), and animals were divided into two groups: low OC group (OC < 2.0 mL/100 g/min) and high OC group (OC ≥ 2.0 mL/100 g/min). RESULTS: In survival analysis, four of seven low OC recipients (57% [n = 7]) survived until the end of the study period compared with one of seven high OC recipients (14% [n = 7]). The low OC group had a significantly higher survival rate than that of the high OC group (P = 0.041). Low OC was associated with higher HAF (mL/100 g/min) after reperfusion compared with that of the high OC group, 29.0 ± 13.8 versus 16.0 ± 11.1 mean ± standard deviation; P = 0.073. Serum alkaline phosphatase and total bilirubin in the low OC group were significantly better than those of the high OC group. Serum lactate was comparable in both groups. Graft weight at the time of sacrifice in the low OC group tended to be higher than that in the high OC group, but not significantly (P = 0.097). CONCLUSIONS: High intraoperative OC is associated with lower HAF, decreased graft function, and decreased survival in the porcine partial liver graft model.

Role of vasodilation during normothermic machine perfusion of DCD porcine livers.

INTRODUCTION: Normothermic machine perfusion (NMP) of the liver is a promising preservation modality that holds the potential to better preserve and even repair marginal grafts. In spite of several literature studies showing the benefits of NMP over cold storage, there is paucity of data regarding the mechanisms involved in the optimization of the microcirculation during preservation of these organs. We present our data on the impact of different vasodilators on DCD porcine livers preserved with NMP. MATERIALS AND METHODS: Livers from 15 female Yorkshire pigs (30-40 kg) were subjected to 60 min of WIT followed by 10 h of NMP. Group PC (n = 5) received a prostacyclin analog (epoprostenol sodium) and the AD group (n = 5) received adenosine, whereas group WV (n = 5) was perfused without using any vasodilator. Liver function was assessed by measuring, liver enzyme levels, bile production rate, and histological analysis. RESULTS: At the end of perfusion, the PC group showed significantly lower AST (583 ± 62 vs. 2471 ± 745 and 2547 ± 690 IU/dl), ALT (41 ± 3 vs. 143 ± 28 and 111 ± 25 IU/dl) and LDH (840 ± 85 vs. 2756 ± 408 and 4153 ± 1569 IU/dl) levels compared to the AD and WV groups respectively (p<0.05). Bile production was significantly higher in the PC group compared to the AD group and WV, respectively (95 ± 9 vs. 37 ± 10 and 45 ± 18ml) (p<0.05). Histological samples of the PC group showed preserved hepatic architecture while those of the AD group and WV showed sinusoidal dilatation, architectural distortion, and profuse intraparenchymal hemorrhage. CONCLUSIONS: Maintenance of optimal microcirculatory homeostasis using proper vasodilators is a key factor in NMP of DCD livers.

Radiologic-histological correlation of hepatocellular carcinoma treated via pre-liver transplant locoregional therapies.

BACKGROUND: Locoregional therapies (LRTs) are treatments to achieve local control of hepatocellular carcinoma (HCC). Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understood. The aim of this study was to evaluate different levels of radiologic response after pre-liver transplant (LT) LRT and its correlation with percentage of tumor necrosis on explanted histopathology. METHODS: Institutional Review Board approved LT database was queried for treated HCC in patients undergoing LT. Radiologic response was evaluated to predict tumor necrosis in the explanted liver. Tumor response was evaluated 1 to 3 months after LRT with computed tomography or MRI via Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) guidelines. LRT was repeated as needed until time of LT. Histological tumor necrosis was graded as complete (100%), partial (50%-99%), or poor (<50%). RESULTS: Between 2002 and 2011, 128 patients (97 men and 31 women) received pre-LT LRT including transarterial therapy (93), radiofrequency ablation (20), or combination of both (15). The mean age of the patients was 58+/-9 years. Their mean follow-up was 35+/-27 months. The median waitlist time was 55 days. One hundred (78%) patients had HCC within the Milan criteria at the initial radiologic diagnosis. Nineteen (15%) of the patients had complete tumor necrosis on histopathology analysis. Fifty (39%) of the patients exhibited partial necrosis, 52 (41%) showed poor or no necrosis and 7 (5%) showed progressive disease. The overall pre-LT radiologic staging was correlated with explant pathology in 73 (57%) of the patients. Underestimated tumor stage was noted in 49 (38%) patients, and overestimated tumor stage in 6 (5%) patients. The post-LT 3-year overall survival and disease free survival were 82% and 80%, and the rates for complete and partial tumor necrosis were 100% vs 78% (P=0.02) and 100% vs 75% (P=0.03), respectively. CONCLUSIONS: In the current era, interpretation of radiologic response after LRT for HCC does not correlate accurately with histologic tumor necrosis. Total tumor necrosis is the goal of LRT; therefore, evolution in its performance is needed. Similarly, ways to predict therapy induced tumor necrosis via radiological investigation need to be improved.

Loco-regional therapy in patients with Milan Criteria-compliant hepatocellular carcinoma and short waitlist time to transplant: an outcome analysis.

OBJECTIVES: Liver transplantation (LT) in Milan Criteria (MC) hepatocellular carcinoma (HCC) has excellent outcomes. Pre-transplant loco-regional therapy (LRT) has been used to downstage HCC to meet the MC. However, its benefit in patients with a brief waiting time to transplant remains unclear. This study evaluated outcomes in patients with short waitlist times to LT for MC-compliant HCC. METHODS: Patients undergoing LT for MC HCC at either of two transplant centres between 2002 and 2009 were retrospectively evaluated for outcome. Patients for whom post-transplant follow-up amounted to <12 months were excluded. RESULTS: A total of 225 patients were included, 93 (41.3%) of whom received neoadjuvant LRT. The median waiting time to transplant was 48 days. Mean post-transplant follow-up was 32.2 months. Overall and disease-free survival at 1 year, 3 years and 5 years were 93.1%, 82.4% and 72.6%, and 91.3%, 79.3% and 70.6%, respectively. There was no difference in overall (P= 0.94) and disease-free survival (P= 0.94) between groups who received and did not receive pre-LT LRT. There were also no disparities in survival or tumour recurrence among categories of patients (with single tumours measuring <3 cm, with single tumours measuring 3-5 cm, with multiple tumours). CONCLUSIONS: Loco-regional therapy followed by rapid transplantation in MC HCC appears not to have an impact on post-transplant outcome.

Predicting the discharge status after liver transplantation at a single center: a new approach for a new era.

The aim of this study was to develop a tool for preoperatively predicting the need of a patient to attend an extended care facility after orthotopic liver transplantation (OLT). A multidisciplinary group, which included 2 transplant surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case manager, 1 home health care professional, 1 rehabilitation physician, and 1 statistician, met to identify preoperative factors relevant to discharge planning. The parameters that were examined as potential predictors of the discharge status were as follows: age, sex, language, Karnofsky score, OLT alone (versus a combined procedure), creatinine, bilirubin, international normalized ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical Model for End-Stage Liver Disease score, renal dialysis, location before transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and right ventricular systolic pressure, sex and availability of the primary caregiver, donor risk index, and donor characteristics. Between January 2004 and April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and 47 patients (6%) underwent combined procedures. Five hundred nineteen patients (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%) died early after OLT. A multivariate logistic regression analysis identified the following parameters as significantly influencing the discharge status: a low Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of 2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI, and renal dialysis before OLT. The nomogram was prospectively validated with a population of 126 OLT recipients with a concordance index of 0.813. In conclusion, a new approach to improving the efficiency of hospital care is essential. We believe that this tool will aid in reducing lengths of stay and improving the experience of patients by facilitating early discharge planning.

The role of the A2a receptor agonist, regadenoson, in modulating hepatic artery flow in the porcine small-for-size liver graft.

BACKGROUND: Hepatic artery vasoconstriction plays a major role in the pathophysiology of the small-for-size (SFS) liver graft injury and is reversed by adenosine. The A2a adenosine receptor (AR) has been suggested to be one of the key receptors that modulate hepatic hemodynamic changes. The aim of the study is to define the effects of the A2a AR agonist, regadenoson, in modulating hepatic artery flow (HAF) in SFS liver grafts of a porcine model. METHODS: Seven female recipient pigs (66-70 kg) receiving 20% liver grafts were treated with regadenoson, 0.1 ug/kg/min starting on POD1 (n = 7). Results were compared with those with untreated 20% liver grafts (n= 8). The recipients were observed for 14 d. Hepatic artery flow (HAF) and portal vein flow (PVF) were recorded. Liver biopsies and serum samples were also taken at the designed time points through postoperative day (POD)14. RESULTS: Dose-response curves of regadenoson established 0.1 ug/kg/min as the most effective dose of regadenoson for maintaining an increase in HAF. No adverse effects were seen with regadenoson infusion. HAF immediately increased by up to 2.2-fold after regadenoson infusion. The levels of daily average of HAF and percentage of HAF in total liver blood flow were 34.5% and 41.8%, respectively, higher in the regadenoson group than in the untreated group. Histologic scores of hepatic artery spasm and bile duct necrosis were significantly lower in the regadenoson group than in the untreated group (P = 0.01 and 0.04, respectively). The complication rates of hepatic artery thrombosis and gastrointestinal bleeding were lower in the regadenoson group than in the untreated group (0/7, 0% versus 2/8, 25% and 0/7, 0% versus 2/8 and 25%, respectively). The 14-d survival rates were 4/7 (57.1 %) in regadenoson group compared with 2/8 (25%) in the untreated group. CONCLUSION: Adenosine A2a AR agonist, regadenoson, increases HAF in the recipients of SFS grafts with modest improvements in outcome.

Elevated catecholamines and hepatic artery vasospasm in porcine small-for-size liver graft.

BACKGROUND: Elevated levels of norepinephrine (NE) have been reported in recipients of small-for-size liver (SFS) grafts in the perioperative period. The aim of the study is to test the hypothesis that although circulating catecholamines are elevated in recipients of SFS grafts, they are not the primary agents responsible for the hepatic artery (HA) vasospasm. METHODS: Female porcine recipients receiving a 20% (n = 10) partial liver graft were compared with a control group, using 60% partial liver transplanted grafts (n = 9). Hepatic blood flow (PVF, HAF) and levels of plasma catecholamines (epinephrine and NE) were measured at designated time points through postoperative day (POD) 7. Phentolamine (PA), an α-adrenergic blocker, was administered at doses of 1 to 112.5 ug/kg/min through an indwelling HA to the recipients of 20% group on POD1 (n = 5). RESULTS: In the 20% group following reperfusion, HA vasospasm was found at 10, 60, and 90 min, and persisted on POD 3 and POD 7. Plasma NE levels increased after reperfusion in 20% and 60% groups and peaked at 6 h with 10- to 13-fold increased levels compared with baseline. In the 20% group, NE levels remained elevated up to POD 7. PA infusion at low (1-10 ug/kg/min) and high (12.5-112.5 ug/kg/min) doses did not reverse the reduced HAF observed in 20% group recipients. CONCLUSION: Elevated serum NE does not appear to be the primary factor mediating HA vasospasm in the porcine SFS graft.

Duct-to-duct biliary reconstruction in patients with primary sclerosing cholangitis undergoing liver transplantation.

BACKGROUND: Reconstruction of biliary drainage after liver transplantation (LTx) in patients with primary sclerosing cholangitis (PSC) has been a matter of controversy. Over recent years, the traditional method of Roux-en-Y hepaticojejunostomy (RY) has been challenged by duct-to-duct (DD) biliary reconstruction. METHODS: This study represents a retrospective review of biliary complications, patient and graft survival after LTx in PSC patients based on type of biliary reconstruction. Outcomes of DD reconstruction in this group of patients and non-PSC patients are compared. RESULTS: A total of 53 primary LTx procedures were performed for PSC between August 2005 and July 2010. Seven patients were excluded because unexpected cholangiocarcinoma was found in the explants (n=3) or because they received partial livers (n=4). Biliary reconstruction was performed as DD in 18 patients and RY in 28 patients. There were no bile leaks. Anastomotic stricture occurred in two (11%) patients in the DD group and one (4%) in the RY group. Two (7%) patients in the RY group developed non-PSC intrahepatic strictures and one had recurrence of PSC. Rates of 1- and 3-year patient and graft survival in the RY and DD groups were 96.7% and 96.7%, and 100% and 94.5%, respectively. In a group of 34 randomly selected patients transplanted for a non-PSC diagnosis with DD reconstruction during the same period, the anastomotic stricture rate was 9% and 1- and 3-year patient and graft survival rates were 97.0% and 88.5%; differences were not significant. CONCLUSIONS: Duct-to-duct biliary reconstruction at the time of LTx in selected PSC patients is both effective and safe, and shows outcomes comparable with those of RY reconstruction in these patients and those of DD reconstruction in non-PSC patients.