List For Liver Transplantation Research Articles

Transarterial Chemoembolization Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) induces ischemic tumor necrosis, which is intensified by regional chemotherapy. By reducing the active tumor tissue, it can be assumed that patients on the waiting list for liver transplantation may benefit from this locoregional treatment. The aim of this study was to assess the relevance of TACE in hepatocellular carcinoma (HCC) patients before liver transplantation. A retrospective analysis was performed on data of 229 patients who were transplanted for HCC. A group of 75 patients were treated with TACE prior to liver transplantation. Tumor necrosis related to pretransplantation locoregional treatment was assessed in an explanted liver and classified into extensive (51-100%), moderate (26-50%) and limited (<25%) grades. Five-year recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. In total, 143 HCC lesions were treated with TACE. Extensive necrosis was found in 63 (44.0%) tumors. Moderate and limited necrosis were observed in 42 (29.4%) and 38 (26.6%) tumors, respectively. In 36 (58.1%) explanted livers, every tumor was classified as extensively necrotic. The 5-year recurrence-free survival was estimated as 81.6% in the group not treated with TACE prior to liver transplantation (TACE-) and as 73.1% in the TACE+ group (p=0.169). Among patients not fulfilling the Milan criteria, 5-year recurrence-free survival was 63.1% in TACE- and 65.1% in TACE+ (p=0.656). In conclusion, TACE prior to liver transplantation is effective in inducing tumor necrosis. However, evidence of benefits in long-term results after liver transplantation requires further confirmation.

Clinical guideline SEOM: hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A–B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with “washout” in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications.

Viral Hepatitis Vaccination Status for Patients on the Liver Transplant Waiting List

Introduction: The incidence of acute hepatitis A or acute or chronic hepatitis B after a liver transplant is rare but can be associated with graft dysfunction or loss. Additionally, with the use of extended criteria donor organs, the presence of a hepatitis B surface antibody allows the recipient the option to receive a hepatitis B-core positive graft. Hepatitis A and B vaccination in liver transplant recipients results in lower rates of antibody formation than in the pretransplant setting. Current AASLD guidelines recommend that all nonimmune liver transplant candidates should receive hepatitis A and B vaccines.Little information is available about the consistent implementation of these recommendations.Our aim was to determine current hepatitis A(HAV) and hepatitis B(HBV) immunity rates for patients on the liver transplant list at a tertiary care center and any associations with unsuccessful vaccinations. Methods: A retrospective chart review was performed of adult patients listed for liver transplantation at a single transplant center as of June 2014.Data collected includes demographics, etiology of cirrhosis, HAV/HBV immune status and vaccination history. To determine immune status, we looked at the presence of serological markers (HBsAg, anti-HBc, anti-HBs, IgG-anti-HAV).Statistical analysis was performed using the student t-test and the Chi-square test to detect any association between immune status and unsuccessful vaccination with patients' demographic data and etiology of cirrhosis. Results: A total of 184 patients (73 females, 111 males) were on the liver transplant list as of June 2014. Mean age was 58. Etiology varied with 35% due to hepatitis C and 18% due to alcohol. 119 (66%) patients were immune to HAV. Of this,15 (13%) had been previously vaccinated with the remaining 104 (87%) developing immunity through prior infection. 48 (27%) patients demonstrated immunity to HBV. Of these, 17 (36%) had evidence of previously cleared infection and the remaining 31 (67%) were vaccinated. 12 patients vaccinated for HBV either never acquired immunity or lost protective antibody over time.There was no statistically significant association between etiology of liver disease and unsuccessful vaccination for HAV (0.500) and HBV (0.517).There was no significant association between HAV immune status and age (0.898), sex (0.918) and etiology of liver disease (0.506).There was also no significant correlation between HBV immune status and age (0.071), sex (0.686) and etiology of liver disease (0.052). Conclusion: The presence of protective antibody for HAV or HBV among patients on the liver transplant waiting list is low, particularly for HBV. This is despite current AASLD recommendations for vaccination of nonimmune patients in the pre-transplant setting. We next hope to identify potential barriers to vaccination and improve immunity rates prior to transplant

Normothermic Perfusion Machine in Liver Transplant With Cardiac Death Donor Grafts

The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilisation rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field.

Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List.

Although renal dysfunction is a known complication of acute liver failure (ALF), its frequency, severity, and impact among patients with ALF on the US liver transplant list are not well defined. Organ Procurement and Transplantation data for ALF patients listed as status 1/1A from 2002 to 2012 were analyzed. The frequency and severity of renal dysfunction at the time of listing [the latter was categorized in 5 stages using estimated GFR (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation] were determined and the association between renal dysfunction and waiting list mortality was assessed using Cox proportional hazard regression analysis. There were a total of 2280 adult patients with ALF, including 56 % with renal dysfunction (defined as eGFR < 60 ml/min/1.73 m(2)) at listing. The highest proportion of patients with renal dysfunction was among those with ALF caused by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, fatty liver disease of pregnancy, heat stroke/hyperthermia, hepatitis A virus, and drug-induced liver injury due to acetaminophen APAP, phenytoin, trimethoprim-sulfamethoxazole, and macrolides. Despite the fact that 69 % (468/674) of patients with APAP-induced ALF listed as status 1/1A had renal dysfunction, only 0.9 % underwent simultaneous liver-kidney transplantation. Six-week survival probabilities in patients with ALF on the liver transplant waiting list were 71, 59, 56, 59, and 42 % with renal dysfunction stages of 1, 2, 3, 4, and 5, respectively. Multivariate analysis showed that after controlling for age, etiology of ALF, INR, total bilirubin, and region, the relative risk of death increased progressively as eGFR declined (P < 0.0001). Among patients with ALF on the liver transplant waiting list, renal dysfunction was common (overall prevalence of 56 %). Most importantly, severe renal dysfunction was associated with significantly increased mortality.

Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis

BackgroundAdvanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis.Materials and MethodsTwo studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed.ResultsPlasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2–24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD-sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively).ConclusionsCirculating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation.

Phases I-II Matched Case-Control Study of Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Disease.

Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with end-stage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 (p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group (p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study.

La máquina de perfusión normotérmica en el trasplante hepático con injertos provenientes de donación en asistolia

The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilization rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field.

Cerebral air embolism during CT-guided lung biopsy

A patient with cirrhosis and hepatocellular carcinoma, on the waiting list for liver transplantation, presented with lung nodule during initial evaluation. A CT-guided core needle lung biopsy under general anaesthesia...

1002 Circumferential Endoscopic Submucosal Dissection of a Squamous Cell Carcinoma in a Cirrhotic Patient With Esophageal Varices

A 47 years old male, recently diagnosed with alcohol-related cirrhosis and mild renal insufficiency, underwent upper gastrointestinal endoscopy as part of the routine examinations for entering the orthotopic liver transplant (OLT) list. Squamous cell carcinoma (SCC) of the distal esophagus (almost circumferential in its extent, with a length of nearly 3 cm) and F2 esophageal varices (EV) were found. Further examinations (CT-scan, EUS) showed that the neoplasia was limited to the mucosa. The patient was a poor candidate for surgery, hence an attempt of endoscopic removal was considered appropriate.

Mo1245 Risk Factors Associated With Overall and Bleeding-Related Mortality in Patients With Portal Vein Thrombosis on the Waiting List for Liver Transplantation

Mo1245 Risk Factors Associated With Overall and Bleeding-Related Mortality in Patients With Portal Vein Thrombosis on the Waiting List for Liver Transplantation

P0156 : Risk factors associated with overall and bleeding-related mortality in patients with portal vein thrombosis on the waiting list for liver transplantation

P0156 : Risk factors associated with overall and bleeding-related mortality in patients with portal vein thrombosis on the waiting list for liver transplantation

P0055 : Safety and efficacy of anticoagulation therapy for portal/splanchnic vein thrombosis in patients with liver cirrhosis on the waiting list for liver transplantation

P0055 : Safety and efficacy of anticoagulation therapy for portal/splanchnic vein thrombosis in patients with liver cirrhosis on the waiting list for liver transplantation

P1316 : Effects of long-term administration of midodrine and albumin in the prevention of complications in patients with cirrhosis on waiting list for liver transplantation. A randomized, multicenter, double-blind, placebo-controlled trial. macht study

P1316 : Effects of long-term administration of midodrine and albumin in the prevention of complications in patients with cirrhosis on waiting list for liver transplantation. A randomized, multicenter, double-blind, placebo-controlled trial. macht study

Mo1012 Safety and Efficacy of Anticoagulation Therapy for Splanhnic Vein Thrombosis in Patients With Liver Cirrhosis on the Waiting List for Liver Transplantation

the time of LT, only 29.5% of patients were considered to be well-nourished. The change in SGA score after the initial nutrition assessment was statistically significant (all p ≤ 0.007). Covariates such as patients gender (p = 0.029), liver disease diagnosis (p = 0.010), biological Model for End-Stage Liver Disease (MELD) score (p= 0.010), time from listing to LT (p= 0.019), transferrin (p= 0.049), albumin (p = 0.003), zinc levels (p= 0.036), vitamin D levels (p = 0.005), and reason for hospital admission (p < 0.001) showed a statistical significance with SGA at initial nutrition visit. 71 patients (62.3%) in our cohort required hospitalization while waiting for LT. The median length of stay (LOS) was 9 days (Range: 177). Hospital LOS showed a statistically significant association with malnutrition status at time of the initial evaluation (p = 0.046), SGA at initial nutrition visit (p= 0.020), liver disease diagnosis (p = 0.001), biological MELD (p < 0.001), days from listing to LT (p = 0.022), transferrin (p = 0.002), albumin levels (p= 0.001), zinc levels (p= 0.008), and vitamin A levels (p < 0.001). Conclusion: In patients awaiting LT, malnutrition was prevalent and usually required nutritional expertise for its diagnosis. Our findings showed despite a lower MELD score and regardless of liver disease diagnosis, malnutrition is common and the degree of malnutrition worsened while waiting for LT. There was an association between hospital LOS pre-LT and patients' malnutrition status. Identification and treatment of malnourished patients with cirrhosis may reduce morbidity and LOS pre-LT.

Hiponatremia dilucional y trasplante hepático. Revisión

Los pacientes con hepatopatías avanzadas pueden presentar estados de hipervolemia que los puede llevar a desarrollar hiponatremia dilucional, la cual se origina principalmente a niveles persistentemente aumentados de hormona antidiurética. El trasplante hepático es la terapia de elección en pacientes con hepatopatías terminales con excelentes sobrevidas en el tiempo. La hiponatremia dilucional ha demostrado ser un factor pronóstico en pacientes con cirrosis e incluso de mortalidad en pacientes en lista de espera para trasplante de hígado. Por tal razón, actualmente hace parte de los puntajes de clasificación de lista de espera de trasplante hepático en pacientes con hepatopatías avanzadas. El papel de la hiponatremia pretrasplante en el pronóstico de pacientes que serán llevados a trasplante hepático es tema de renovado interés, con datos en la literatura bastante contradictorios. Hasta hace poco, solo la restricción hídrica era el tratamiento contra la hiponatremia dilucional; sin embargo, actualmente se dispone de tratamientos dirigidos contra la hipona- tremia dilucional en pacientes con cirrosis con resultados algo alentadores, aunque poco se sabe sobre su efecto en pacientes con cirrosis que serán llevados a trasplante hepático.

List and Liver Transplant Survival According to Waiting Time in Patients With Hepatocellular Carcinoma

The time that patients with hepatocellular carcinoma (HCC) can safely remain on the waiting list for liver transplantation (LT) is unknown. We investigated whether waiting time on the list impacts transplant survival of HCC candidates and transplant recipients. This is a single-center retrospective study of 283 adults with HCC. Patients were divided in groups according to waiting-list time. The main endpoint was survival. The median waiting time for LT was 4.9 months. The dropout rates at 3-, 6-, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Mortality on the list was 4.8%, but varied depending of the time on the list. Patients who waited less than 3-months had an inferior overall survival when compared to the other groups (p = 0.027). Prolonged time on the list significantly reduced mortality in this analysis (p = 0.02, HR = 0.28). Model for End Stage Liver Disease (MELD) score at transplantation did also independently impact overall survival (p = 0.03, HR = 1.06). MELD was the only factor that independently impacted posttransplant survival (p = 0.048, HR = 1.05). We conclude that waiting time had no relation with posttransplant survival. It is beneficial to prolong the waiting list time for HCC candidates without having a negative impact in posttransplant survival.

Serum sodium and survival benefit of liver transplantation.

Hyponatremia is associated with elevated wait-list mortality among end-stage liver disease candidates for liver transplantation (LT). However, the effect of low serum sodium on the survival benefit of LT has not been examined. We sought to determine whether pretransplant hyponatremia is associated with an altered LT survival benefit. Data were obtained from the Scientific Registry of Transplant Recipients. The study population consisted of adults (age ≥ 18 years) placed on the waiting list for LT between January 1, 2005 and December 31, 2012 (n = 69,213). The effect of hyponatremia on the survival benefit was assessed via sequential stratification, an extension of Cox regression. Each transplant recipient was matched to appropriate candidates then active on the waiting list with the same Model for End-Stage Liver Disease (MELD) score and in the same donation service area. The focus of the analysis was the interaction between the serum sodium and the MELD score with respect to the survival benefit of LT; this was defined as the covariate-adjusted hazard ratio contrasting post-LT mortality and pre-LT mortality. The LT survival benefit increased significantly with decreasing serum sodium values when the MELD scores were >11. The survival benefit of LT was not affected by serum sodium for patients with MELD scores ≤ 11. In conclusion, the LT survival benefit (or lack thereof) is independent of serum sodium for patients with MELD scores ≤ 11. The increase in the survival benefit with decreasing serum sodium among patients with MELD scores > 11 is consistent with recently approved changes to the allocation system incorporating serum sodium.

Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir + ribavirin: possible clinical implications in the liver transplant list management

Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir + ribavirin: possible clinical implications in the liver transplant list management

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