Evaluation For Orthotopic Liver Transplantation Research Articles

Assessment of Vascular and Valvular Calcification Improves Screening for Coronary Artery Disease Before Liver Transplantation

Coronary artery disease (CAD) is common in patients with cirrhosis who underwent orthotopic liver transplantation (OLT) evaluation and stress echocardiogram (echo) has a low sensitivity in these patients. This study aimed to assess the impact of vascular and valvular calcification on the ability to identify CAD before OLT. We performed a case-control study of 88 patients with and 97 without obstructive CAD who underwent OLT evaluation. All patients had a preoperative stress echo, abdominal computed tomography, and cardiac catheterization. A series of nested logistic regression models of CAD were fit by adding independent variables of vascular (including coronary) calcification, aortic and mitral valve calcification, age, gender, and history of diabetes mellitus requiring insulin to a baseline model of abnormal stress echo. Compared with stress echo alone, identification of the presence or absence of vascular and valvular calcification on routine preoperative computed tomography and echo improved the diagnostic performance for the detection of CAD based on coronary angiogram when combined with stress echo in patients with cirrhosis who underwent OLT evaluation (area under the curve 0.58 vs 0.73, p <0.001), which is even further improved when age, gender, and history of diabetes mellitus requiring insulin are considered (area under the curve 0.58 vs 0.80, p <0.001). Achieving target heart rate (p=0.92) or rate-pressure product >25,000 (p=0.63) did not improve the ability of stress echo to identify CAD. In conclusion, the use of abdominal vascular, coronary artery, and valvular calcification, along with stress echo, improves the ability to identify and rule out obstructive CAD before OLT compared with stress echo alone.

Cardiology Assessment of Patients Undergoing Evaluation for Orthotopic Liver Transplantation.

Orthotopic liver transplantation (OLT) is a viable treatment option for end-stage liver disease. Significant perioperative stress is placed on the cardiovascular system because of hemodynamic changes and the length of the operation. Diagnosis and treatment of cardiovascular disease before OLT are imperative to ensure favorable outcomes. Considerable variability exists among practitioners caring for these patients. Institutions tailor their protocols on the basis of local and historical practices, the preferences of the cardiologists, and the OLT team, and algorithms are not often revised or updated on the basis of the available evidence. In collaboration with cardiology and hepatology experts from leading OLT centers, we sought to examine the diagnostic cardiovascular workup of OLT candidates, including a review of the available literature on the diagnostic modalities used to screen cardiovascular disease before OLT. We advocate an emphasis on noninvasive methods to assess cardiovascular risk with reserved use of invasive risk stratification in select patients.

S1286 Impact of Cardiovascular Disease on Liver Transplant Candidacy During Transplant Evaluation in a North American Center With High Obesity Prevalence

Introduction: There are no large studies that examined the impact of obesity and cardiovascular disease in patients undergoing evaluation for orthotopic liver transplantation (OLT). Methods: We retrospectively analyzed patients undergoing OLT evaluation between Jan 2012 and Nov 2021 in a liver transplant center in the Mid-West US. Results: 912 patients underwent OLT evaluation (59% males, mean age 57.4±10.5 years, Mean Na-MELD 18.7±8.7, 82% Caucasian and 8.6% African Americans) etiology of cirrhosis NASH (48.1%), alcohol (37.7%), and hepatitis C (18.5%). 31.8% and 41.7% were overweight and obese respectively. 261 (31.8%) underwent OLT, 554 (60.7%) were denied listing, and 51(5.6%) died during evaluation. 224 patients had coronary artery disease (CAD) and among them, 50% were denied OLT. Of all patients denied listing, 32% were denied OLT due to CAD. Comorbid medical conditions (30%), substance use (15%) and socioeconomic condition (19.3%) were other causes for denial for listing. 239 (26.2%) had metabolic syndrome (MS), of which 143 (59.8%) were denied OLT. Among patients denied, 55(10%) were morbidly obese (BMI >40). Gender, residential location(urban v/s rural), hypertension, diabetes, CAD, BNP levels, atrial fibrillation, chronic kidney disease, hyperlipidemia,MS,6-minute walk test (6MWT) did not correlate with transplant denial on univariate analysis (Table). Ethnicity (African American, p=0.03), vitamin-D deficiency (< 30 ng/ml) and BMI (p=0.038) had significant correlation. On multivariate analysis (MVA), BMI >30), (OR 0.71 [0.51-0.98], p = 0.04) and vitamin-D deficiency (OR 0.21 (0.15-0.29), p < .01) were independent predictors of denial. For predicting death during OLT evaluation, on univariate analysis, 6-minute walk test (6MWT), estimated pulmonary artery pressure (PAP) on transthoracic echocardiography, mean PAP on right heart catheterization, significant coronary obstruction on left heart catheterization were not predictors, but female gender and vitamin-D deficiency were predictors. On stratified analysis of patients denied listing due to CAD, the presence of MS (OR 2.1(1.3-3.5), p=0.003) was an independent predictor of denial, and normal BNP levels (< 100pg/ml) lowered the risk of denial (OR 0.42 (0.20-0.88), p=0.02). Conclusion: Obesity (BMI >40) and vitamin-D deficiency increased the risk of denial for transplant listing. Presence of metabolic syndrome increased the risk of denial for listing due to CAD and normal BNP levels (< 100pg/ml) significantly lowered the risk of denial from CAD. Table 1. - Univariate analysis for predictors of liver transplant denial and death in waiting list Transplant denial (p value) Death during evaluation (p value) Gender 0.09 0.04* Ethnicity 0.03* 0.21 Location (rural v/s urban) 0.15 0.5 Hypertension 0.86 0.41 Diabetes 0.81 0.98 BMI 0.04* 0.59 CAD 0.55 0.42 Chronic kidney disease 0.06 0.16 Atrial fibrillation 0.73 0.96 Hyperlipidemia 0.66 0.22 Metabolic syndrome 0.68 0.77 Vitamin-D deficiency < 0.01* < 0.01* 6 Minute Walk Test (6MWT) 0.67 0.56 BNP levels 0.19 0.65 Cardiac ejection fraction on echocardiography 0.58 Elevated estimated PAP 0.81 Elevated mean PAP 0.12 Computed tomography calcium score 0.35 Positive dobutamine stress echocardiography 0.68 Significant coronary obstruction in left heart catheterization 0.44

Alcohol-related cirrhosis is associated with high coronary artery calcium scores in patients undergoing evaluation for orthotopic liver transplantation.

Coronary artery disease is a major cause of morbidity and mortality in liver transplant patients. Coronary artery calcium (CAC) score has been used to evaluate the risk of CAD in non-cirrhotic patients. However, its significance in cirrhotic patients is unknown. This study aimed to identify factors associated with elevated CAC scores in patients with end-stage liver disease undergoing liver transplant evaluation. We retrospectively reviewed all patients who underwent liver transplantation evaluation and had coronary CT scan between January 2015 and December 2018. Patients with prior history of CAD were excluded. CAC score was calculated based on the method described by Agatston. Sixty-two patients were included. 37.1% had alcohol-related liver disease and 27.4% had NASH cirrhosis. Mean CAC score was 261.1±SD, 463.84. Alcohol-related liver disease, male gender, and hypertension were significantly associated with CAC score >100 and only alcohol-related liver disease was associated with CAC score >300. In logistic regression, patients with alcohol-related liver disease had more than sixfold increase in risk of having CAC scores >100 and 300 (OR 6.14, and 6.70, respectively). Alcohol-related liver disease, male gender, and hypertension were significantly associated with an increased CAC score >100. However, alcohol-related liver disease was the only factor associated with CAC score >300.

Pulmonary Fibrosis Uncovered during Evaluation for Orthotopic Liver Transplantation.

Pulmonary Fibrosis Uncovered during Evaluation for Orthotopic Liver Transplantation.

2281 Symptomatic Isolated Polycystic Liver Disease Causing Respiratory Compromise

INTRODUCTION: Isolated Polycystic Liver Disease (PCLD) is defined by the presence of more than 20 hepatic cysts. It has an autosomal dominant inheritance and is largely asymptomatic with only 5% of patients who report pain or other complaints. The disorder is considered rare with an estimated incidence of &lt; 0.01%. We present a case of isolated PCLD causing respiratory failure. CASE DESCRIPTION/METHODS: A 45-year-old woman with history of an isolated liver cyst, was admitted for acute respiratory failure. No significant family history. On physical exam, oxygen saturation was 98% on 2 liters nasal cannula. She had prolonged expiratory phase, decreased breath sounds and marked hepatomegaly. FEV1 = 23%, FEV1/FVC = 117%. Liver studies were significant for alkaline phosphatase 131 IU/L and albumin 3.3 gm/dl. Abdominal CT showed a markedly enlarged liver measuring 21 cm, liver volume of 3588 ml and the presence of numerous thin-walled-fluid-filled cysts ranging from 2 mm to 4 cm, consistent with PCLD. It was determined that the mass effect from the liver pressing against the diaphragm was the cause of her respiratory failure. She was started on BiPAP with improvement of respiratory function. She underwent evaluation for orthotopic liver transplantation(OLT) but was not a candidate due to high risk for hypercarbic respiratory failure, and prolonged mechanical ventilation. She was discharged on non-invasive ventilation with oxygen supplementation and was scheduled for re-evaluation for OLT. DISCUSSION: Isolated PCLD is caused by germline mutations of the PRKCSH and SEC63 genes. Genetic testing is rarely necessary and does not affect management. Liver function is often altered once symptoms develop. The number and size of liver cysts often increase with age. Women often present with a massive and symptomatic cystic liver more frequently than men and symptoms are likely attributed to the compression of adjacent organs due to mass effect, which often leads to poor body image and depression. When symptoms develop they include pain, nausea, early satiety, vomiting, or dyspnea. Complications are rare and can include infection, portal hypertension, and Budd-Chiari Syndrome. Treatment includes aspiration-sclerotherapy, laparoscopic or open surgical fenestration techniques, and hepatectomy. Somatostatin analogues show promise. Liver transplantation may be required in extensive disease. One should be cognizant that symptomatic isolated PCLD often leads to greatly diminished quality of life.

Significance of Coronary Artery Calcium Found on Non–Electrocardiogram-Gated Computed Tomography During Preoperative Evaluation for Liver Transplant

Guidelines to evaluate patients for coronary artery disease (CAD) during preoperative evaluation for orthotopic liver transplantation (OLT) are conflicting. Cardiac catheterization is not without risk in patients with end-stage liver disease. No study to date has looked at the utility of non-electrocardiogram-gated chest computed tomography (CT) in the preliver transplant population. Our hypothesis was that coronary artery calcium scores (CACSs) from chest CT scans ordered during the liver transplant workup can identify patients who would benefit from invasive angiography. Nine hundred and fifty-three patients who underwent coronary angiography as part of their OLT workup were considered. Charts were randomly selected and reviewed for the presence of a chest CT performed before coronary angiography during the OLT workup. Agatston and Weston scores were calculated. CACS results were compared with coronary angiography findings. Nine of 54 patients were found to have obstructive CAD by angiography. Receiver-operating characteristic analysis demonstrated that an Agatston score of 251 and a Weston score of 6 maximized sensitivity and specificity for detection of obstructive coronary disease. An Agatston score <4 or Weston score <2 excluded the presence of obstructive CAD; using these thresholds, 13 patients (24%) or 15 patients (28%), respectively, could have theoretically avoided catheterization without missing significant CAD. In conclusion, our data identify the strength of CACS in ruling out coronary disease in patients being evaluated for OLT. Calcium scoring from non-electrocardiogram-gated CT studies may be integrated into preoperative algorithms to rule out obstructive CAD and help avoid invasive angiography in this high-risk population.

Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation.

Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n = 132), initial screening was more common via stress testing (n = 100; 75.8%) than coronary angiography (n = 32; 24.2%). Most with initial stress testing underwent angiography (n = 52; 39.4%). Among those undergoing angiography, CAD was common (n = 31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07–3.44, p = 0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols.

From Listing to Transplant: Nephrologic Monitoring in Cirrhotic Patients Awaiting Liver Transplantation

Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

Dobutamine stress echocardiography in patients undergoing orthotopic liver transplantation: a pooled analysis of accuracy, perioperative and long term cardiovascular prognosis

Pre-transplant evaluation for orthotopic liver transplantation (OLT) commonly includes a cardiac evaluation using dobutamine stress echocardiography (DSE). We performed a quantitative systematic review assessing DSE's use in detecting coronary artery disease (CAD) and predicting perioperative and long term cardiac events in patients undergoing OLT. Published studies in pubmed were accessed using keyword searches and bibliographic review. Included studies evaluated the use of DSE in patients undergoing OLT, including its accuracy for detection of CAD, and in predicting perioperative and long term cardiac prognosis for both hard (myocardial infarction, cardiac death, cardiac arrest, and asystole) and soft cardiac events (all other events that were cardiovascular in nature). We calculated DSE's sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) in the above areas. We identified 7 studies, including a total of 580 patients, which included 4 accuracy studies (n=110 patients), 4 perioperative studies, and 3 long term studies. Accuracy for CAD included a sensitivity of 0.32, specificity of 0.78, PPV of 0.37, and NPV of 0.75. Accuracy for prediction of perioperative hard and soft cardiac events was a sensitivity of 0.20 and 0, specificity of 0.99 and 0.99, PPV of 0.33 and 0, and NPV of 0.98 and 0.89, respectively. For long term hard and soft cardiac events, sensitivity was 0.5 and 0, specificity 0.99 and 0.98, PPV 0.33 and 0, and NPV 0.99 and 0.96, respectively. DSE has a limited accuracy for the detection of CAD in candidates for OLT. However, among those patients selected for OLT, the negative predictive value of DSE for both perioperative and long term cardiac events is high.

Oral direct-acting antiviral therapy to prevent reinfection of the liver graft after liver transplantation for hepatitis C virus-related cirrhosis

Hepatitis C virus (HCV) remains the most common indication for orthotopic liver transplantation (OLT) and universally reinfects the new liver graft; as a result, patients with HCV have poorer outcomes than patients undergoing OLT for non–HCV-related cirrhosis.1 Recently, new direct-acting antiviral (DAA) agents have been approved for genotype 1 HCV infections in combination with peginterferon/ribavirin (RBV).2, 3 However, these therapies may be associated with morbidity and mortality when they are given to patients with advanced liver disease.4 We report a sustained response with an oral DAA/RBV combination without interferon in a 61-year-old male with HCV genotype 1b (interleukin-28B TT) who underwent OLT at our center for HCV-related cirrhosis. He presented to our center for an OLT evaluation with a Model for End-Stage Liver Disease (MELD) score of 18 as well as ascites and encephalopathy, and interferon and RBV had previously failed in 1999. Once listed, he requested therapy with peginterferon/RBV and a DAA agent while he was awaiting OLT. Because of his ascites, encephalopathy, and MELD score, this was not offered. However, his HCV RNA viral level was found to be low at 887 IU/mL (Cobas TaqMan HCV assay), so telaprevir (TVR; 750 mg every 8 hours) and RBV (1200 mg daily) were initiated. At week 1 of therapy, his HCV RNA level was <43 IU/mL (target not detected). Because of gastrointestinal side effects at week 1 (nausea and diarrhea), he was converted to boceprevir (BOC; 800 mg every 8 hours) with RBV and underwent OLT 9 weeks after the initiation of therapy with a MELD score of 19. There were no additional episodes of decompensation, and he did not require transfusions, although an RBV dose reduction to 600 mg was required. Just before surgery, he took BOC (800 mg) as well as RBV (400 mg). Twenty-four weeks after OLT, he remained a sustained responder (Fig. 1). Recent reports have demonstrated that a sustained virological response (SVR) can be achieved in HCV patients without interferon, although no studies to date have included patients with decompensated cirrhosis.5 However, to our knowledge, this represents the first successful cure of HCV in which DAA therapy without interferon was used to suppress the virus before OLT in a patient with decompensated liver disease in whom interferon was contraindicated. It should be emphasized that this case was unique because of the very low viral level and the more favorable genotype 1b infection. In addition, our patient was able to undergo OLT with a MELD score of 19, which is a level below the national median MELD score for deceased transplants in 2011.6 These factors allowed the combination of TVR and RBV followed by BOC with RBV to achieve viral suppression without the emergence of viral resistance. Because BOC may be administered for up to 44 weeks, our patient could have continued to receive BOC with RBV if no donor had been available, although it is unknown whether a breakthrough would have occurred with a longer duration of therapy. The vast majority of patients with genotype 1 infections who present for listing for OLT will have a viral level significantly higher than our patient's level (typically 104−106 IU/mL), and this level in our opinion would contraindicate our approach in this report because of the risk of treatment futility and resistance with nonstructural protein 3 protease inhibitors and RBV. However, more effective, all-oral DAA combinations with high barriers to resistance are currently being studied that can achieve high SVR rates in patients with high viral levels, and we believe the approach of DAA combinations without interferon may serve as a model for preventing reinfection of the liver graft and improving the survival of HCV-infected individuals who require OLT. Paul Y. Kwo, M.D.1 A. Joseph Tector, M.D., Ph.D.2 Departments of 1Medicine and 2Transplant SurgeryIndiana University School of MedicineIndianapolis, IN

Orthotopic Liver Transplantation in a Multiethnic Population: Role of Spatial Accessibility

Introduction Access to orthotopic liver transplantation (OLT) varies among different ethnic groups. The aim of this study was to determine if distance from transplantation center (DT) impedes referral pattern and accessibility to OLT among ethnic groups. Method This is a retrospective cohort study of all patients evaluated for OLT at our center (2002–2007). The ZipCode Basic software was used to compute distance between the candidate's residence and transplantation center. Results Five hundred one patients were evaluated during the study period and there were 439 (87.6%) whites 43 (8.6%) African Americans (AA), and others (3.8%). The median DT was 36.8 miles (range, 0.5–231), and there was no significant correlation with the Model for End-Stage Liver Disease (MELD) at presentation ( P = .87). Although AA had a higher likelihood of residing closer to a transplantation center they were more likely to have a higher MELD at presentation (20 vs 15.4; P < .001) and less likely to be referred early to initiate OLT evaluation (11.6% vs 26.4%; P = .04). Additionally, type of insurance correlated with higher MELD at presentation. Conclusion DT was not a contributory factor to the observed access disparity in our patient population, rather the insurance type and disease severity as determined using MELD differed significantly among ethnic groups.

Liver transplantation of patients with cryptogenic cirrhosis: Clinical characteristics and outcome

Objectives. Non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH) and unapparent alcohol abuse may be underlying causes of cryptogenic cirrhosis, but the frequencies of these underlying factors differ between studies. Also, previous studies have shown various outcomes after orthotopic liver transplantation (OLT) for cryptogenic cirrhosis. The aims of this study were (1) to evaluate the presence of NAFLD in patients with cryptogenic cirrhosis evaluated for OLT and (2) to compare the severity of liver disease and patient survival in OLT candidates with cryptogenic cirrhosis and those with cirrhosis of another known origin. Material and methods. Four-hundred and seventy adult patients with end-stage liver cirrhosis evaluated for OLT between 1990 and 2004 were included, of whom 39 had cryptogenic cirrhosis. Clinical, histological and laboratory data that had been prospectively collected were re-evaluated. Results. Seventeen (44%) of the cryptogenic patients had NAFLD in a previous liver biopsy and/or clinical features of the metabolic syndrome. Two patients had occult alcohol over-consumption and one patient had burnt-out AIH. Cryptogenic patients had significantly higher frequencies of diabetes, ascites, and hyponatraemia and weight loss. Patient survival was similar between cryptogenic patients and cirrhotics with a known aetiology. Conclusions. Re-evaluation of patient data discovered probable underlying aetiologies in 51% of patients with cryptogenic cirrhosis evaluated for OLT, of which NAFLD was the most common (44%). Although cryptogenic patients had a more advanced liver disease when evaluated for OLT, patient survival was similar. Recent weight loss was significantly more common in cryptogenic patients, possibly being a sign of liver decompensation and signalling a need for OLT evaluation.

Smoking behavior in liver transplant recipients

Long-term morbidity and survival after orthotopic liver transplantation (OLT) are to a large degree determined by cardiovascular disease and cancer. Tobacco use is a well-known risk factor for both. The aim of this study was to examine smoking behavior before and after OLT and to define groups at risk for resuming tobacco use after OLT. In addition, we looked for a relation between smoking and morbidity after OLT. All 401 adult patients with a follow-up of at least 2 years after OLT were included. Data were collected from the charts. A questionnaire about smoking habits at 4 time points before and after OLT was sent to all 326 patients alive, and 301 (92%) patients responded. Both before and after OLT, 53% of patients never used tobacco, and around 17% were active smokers. Of the active smokers during the evaluation for OLT, almost one-third succeeded in cessation, often during the waiting time for OLT. Twelve percent of former smokers restarted smoking, mainly after OLT. Tobacco use was the highest in patients with alcoholic liver disease (52% were active smokers before OLT, and 44% were after OLT) and the lowest in patients with primary sclerosing cholangitis (1.4% were active smokers before OLT). At 10 years, the cumulative rate of malignancies was 12.7% in active smokers versus 2.1% in nonsmokers (P = 0.019). No effect on skin cancer or cardiovascular disease was found. In conclusion, smoking is a serious problem after OLT and increases the risk for malignancy. Prevention programs should focus not only on active smokers but also on former smokers.

Clinical Utility of Electrophysiological Evaluation in Crigler-Najjar Syndrome

We evaluated the neurological and neurophysiological features in ten patients with genetically characterized Crigler-Najjar (CN) syndrome: four with typical type I CN had undergone orthotopic liver transplantation (OLT); six had type II CN, and three of them developed severe hyperbilirubinemia with a limited response to phenobarbital leading to an intermediate phenotype I/II. Clinical neurological and multimodal electrophysiological evaluations [electroencephalogram (EEG), visual (VEPs), motor (MEPs) and brainstem auditory (BAEPs) evoked potentials] were performed. Neurological examinations showed mild hand tremor in four patients (one pre-OLT and one post-OLT type I, two type I/II). EEG revealed high voltage paroxysmal discharges in four patients (three type I/II, and one type I with a marked improvement after OLT). VEPs showed P100 wave increased latency in five patients (three type I, and two type I/II considered for OLT evaluation). MEPs showed prolonged central motor conduction time in five patients (two type I; one type I/II; two type II). Only EEG and VEPs findings showed a correlation with high bilirubin levels. BAEPs were normal. In conclusion, VEPs and EEG contribute to identify and monitor bilirubin neurotoxic effects, and may play a decisional role in some cases of severe hyperbilirubinemia without overt neurologic damage.

SILDENAFIL REDUCES PULMONARY VASCULAR RESISTANCE ALLOWING FOR ORTHOTOPIC LIVER TRANSPLANTATION IN PATIENTS WITH PORTOPULMONARY HYPERTENSION: AN OPEN-LABEL, SINGLE-CENTER REPORT

PURPOSE: Portopulmonary hypertension occurs in 6-15% of advanced cirrhosis patients undergoing evaluation for orthotopic liver transplantation. Pulmonary arterial hypertension (PAH) increases peri-operative cardiovascular mortality and is an absolute contraindication when patients have a mean pulmonary arterial pressure (mPAP) > 40mmHg. Most reports have used parenteral prostanoid therapy to treat PAH in these patients; drug therapy is complex and many patients are interested in alternatives.

Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database

Background Orthotopic liver transplantation (OLT) is the only treatment option for unresectable hepatoblastoma (HB) and hepatocellular carcinoma (HCC) in children. Aggregated outcomes of OLT for these hepatic malignancies have not been evaluated in the United Network for Organ Sharing national database. Purpose The purpose of this study was to evaluate graft and patient survival in pediatric OLT recipients with HB and HCC. Methods Data from the United Network for Organ Sharing Standard Transplant and Research Files were analyzed and included pediatric (<18 years) OLT recipients with HB or HCC from 1987 to 2004. The effects of diagnosis on pretransplant variables were evaluated using analysis of variance methods or χ 2 tests, as appropriate. Actuarial survival and effect of diagnosis on survival were determined using Kaplan-Meier methods and log-rank tests. Results Since 1987, 152 OLTs have been performed in 135 pediatric patients for HB and 43 OLTs in 41 pediatric patients for HCC. Respective 1-, 5-, and 10-year patient survival after OLT was 79%, 69%, and 66% for HB and 86%, 63%, and 58% for HCC ( P = .73). The primary cause of death for both groups was metastatic or recurrent disease, accounting for 54% of deaths in the HB group and 86% in the HCC group ( P = .338). Patients with hepatoblastoma were younger (mean age, 2.9 ± 2.5 vs 10.4 ± 4.8 years for the HCC group; P < .001) and more likely to receive a living donor organ (16% vs 4%, P = .03). A greater proportion of the patients with HB had previous abdominal surgery than patients with HCC (63% HB vs 37% HCC, P = .04). Pretransplant medical condition and transplant era were associated with graft and patient survival on univariate and multivariate analysis (all P < .05). Conclusions Orthotopic liver transplantation remains a viable option for pediatric patients with unresectable primary hepatic malignancies and results in good long-term survival. Pretransplant medical condition is an important predictor of outcome. Thus, in conjunction with better chemotherapy regimens, earlier evaluation for OLT in patients with unresectable HB and HCC may result in yet further improved long-term survival.

Liver transplantation for patients with metastatic endocrine tumors: Single-center experience with 15 patients

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.

Management of end stage liver disease (ESLD): What is the current role of orthotopic liver transplantation (OLT)?

Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Orthotopic liver transplantation in a malignant hyperthermia susceptible patient

We present a patient with hepatitis C and D and hepatocellular carcinoma who underwent preoperative evaluation for orthotopic liver transplantation. In his past medical history, he reported a life-threatening event during tonsillectomy in 1975. Intubation was impossible due to extreme jaw muscle tension, followed by excessive elevation in body temperature, tachycardia, and coma for a few days. We evaluated him for malignant hyperthermia, according to the European Malignant Hyperthermia Group Protocol, and found him highly positive in both the halothane and caffeine test, respectively. Three months later, we performed an orthotopic liver transplantation. During retransplantation 4 years later, due to ischemic-type biliary lesions, he suffered massive intraoperative bleeding. Blood products, as well as coagulation factors and aprotinin, were well tolerated. Anesthesia was performed in a trigger-free total intravenous technique without dantrolene prophylaxis, but dantrolene was readily available in sufficient quantities in the operating room. The patient did not encounter a malignant hyperthermia crisis in either perioperative period.