End Stage Liver Disease

Persons at high risk for human immunodeficiency virus (HIV) infection are also likely to be at risk for other infectious pathogens, including hepatitis B virus (HBV) or hepatitis C virus (HCV). These are bloodborne pathogens transmitted through similar routes; for example, via injection drug use (IDU), sexual contact, or from mother to child during pregnancy or birth. In some settings, the prevalence of coinfection with HBV and/or HCV is high. In the context of effective antiretroviral therapy (ART), liver disease has emerged as a major cause of morbidity and mortality in HIV-infected persons. Further, coinfection with viral hepatitis may complicate the delivery of ART by increasing the risk of drug-related hepatoxicity and impacting the selection of specific agents (e.g., those dually active against HIV and HBV). Expert guidelines developed in the United States and Europe recommend screening of all HIV-infected persons for infection with HCV and HBV and appropriate management of those found to be chronically infected. Treatment strategies for HBV infection include the use of nucleos(t)ide analogues with or without anti-HIV activity and/or peginterferon alfa (PegIFN) whereas HCV treatment is limited to the combination of PegIFN and ribavirin (RBV). Current approaches to management of HIVinfected persons coinfected with HBV or HCV are discussed in this review.

Biliary hamartomas or von-Meyenburg complexes form part of a spectrum of ductal plate malformation that includes polycystic liver disease, congenital hepatic fibrosis, and Caroli disease. These lesions are known to have neoplastic transformation. Development of intrahepatic cholangiocarcinoma is well described in these complexes. Rarely, hepatocellular carcinomas (HCCs) have been seen in association with bile duct hamartomas, however; it is not clear whether development of HCC is an epiphenomenon unrelated to the precursor lesion or biliary hamartomas may progress to liver cancers. We herein report 4 interesting cases of hepatitis C virus-, alcohol-, and nonalcoholic fatty liver diseaseassociated end-stage liver disease with coexisting HCC and multiple large von-Meyenburg complexes.

Introduction Gastrointestinal bleeding is a common life-threatening problem, causing significant mortality, costs and resource allocation. Its management requires a dynamic multidisciplinary approach that directs diagnostic and therapeutic priorities appropriately. Materials and methods Articles published within the past 15 years, related to gastrointestinal bleeding, were reviewed through MEDLINE search, in addition to current guidelines and standards. Results Decisions of ICU admission and blood transfusion must be individualized based on the extent of bleeding, hemodynamic profile and comorbidities of the patient and the risk of rebleeding. A secure airway may be required to optimize oxygenation and to prevent aspiration. Doses of induction agents must be reduced due to the changes in volume of distribution. Volume replacement is the cornerstone of resuscitation in profuse bleeding, but nontargeted aggressive fluid resuscitation must be avoided to allow clot formation and to prevent increased bleeding. Decision to give blood transfusion must be based on physiologic triggers rather than a fixed level of hemoglobin. Coagulopathy must be corrected and hypothermia avoided. Need for massive transfusion must be recognized as early as possible, and a 1:1:1 ratio of packed red blood cells, fresh frozen plasma and platelets is recommended to prevent dilutional coagulopathy. Tromboelastography can be used to direct hemostatic resuscitation. Transfusion related lung injury (TRALI) is a significant problem with a mortality rate approaching 40%. Prevention of TRALI is important in patients with gastrointestinal bleeding, especially among patients having end-stage liver disease. Preventive strategies include prestorage leukoreduction, use of male-only or never-pregnant donors and avoidance of long storage times. Management of gastrointestinal bleeding requires delicately tailoring resuscitation to patient needs to avoid nonspecific aggressive resuscitation. “Functional hemodynamic monitoring” requires recognition of indications and limitations of hemodynamic measurements. Dynamic indices like systolic pressure variation are more reliable predictors of volume responsiveness. Noninvasive methods of hemodynamic monitoring and cardiac output measurement need further verification in patients with gastrointestinal bleeding. Conclusions Management of gastrointestinal bleeding requires a dynamic multidisciplinary approach. The mentioned advances in management of hemorrhagic shock must be considered in resuscitation and monitoring of patients with GI bleeding.

Patients with end-stage liver disease (ESLD) frequently have diverse abnormalities of carbohydrate, lipid, and protein metabolism that cause progressive deterioration of their clinical condition and lead to malnutrition. Malnutrition is almost universally present in patients with ESLD undergoing liver transplantation and has been associated with increased morbidity and mortality. It is essential to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation. In conclusion, this article reviews the etiologic factors, prevalence, assessment and management guidelines of nutritional disorders seen in patients with ESLD undergoing liver transplantation.

Liver transplantation is still the only effective treatment for end-stage liver disease. However, because of the serious worldwide shortage of donated organs, an alternative cellular therapy would be desirable. Animal studies and preclinical trials have indicated that hepatocyte transplantation can serve as an alternative to liver transplantation. Unfortunately, however, the harvesting of hepatocytes is associated with the same problem as organ transplantation, i.e., a lack of a suitable cell source. Therefore, current stem cell technology, which is attempting to establish an unlimited supply of hepatocytes, would facilitate the clinical application of hepatocyte transplantation. This review summarizes current knowledge of embryonic and adult stem cell differentiation into hepatocytes and discusses how liver stem cells could be applied clinically in the future.

Cognitive impairment is common among patients with end-stage liver disease (ESLD). This study examined cognitive dysfunction in patients with ESLD using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHOD: 66 patients with ESLD awaiting liver transplant were recruited. Patients were evaluated with the RBANS, Peabody Picture Vocabulary Test-Revised, and Beck Depression Inventory-II. RESULTS: Patients with ESLD uniformly performed below expectations on all RBANS index scores compared to the healthy normative sample (all p's < .0001) and they also displayed a "subcortical" pattern of cognitive performance (p < .0001). Performances on RBANS attention, language, immediate memory, and total index scores were correlated with education and ethnicity (r's range = |.32-.57|; p's < .01). There was no association between performance on any of the RBANS index scores or subtests and ESLD patient characteristics. In summary, the RBANS appears to adequately characterize known patterns of cognitive dysfunction in ESLD patients.

Protein-energy malnutrition is frequently seen in patients with end-stage liver disease who undergo liver transplantation. This causes a deterioration of the patients' clinical condition and affects their post-transplantation survival. Accurate assessment of the nutritional status and adequate intervention are prerequisites for perioperative nutritional treatment. However, the metabolic abnormalities induced by liver failure make the traditional assessment of the nutritional status difficult. The methods that were recently developed for accurately assessing the nutritional status by body bioelectrical impedance may be implemented in pre-transplant management. Because preoperative malnutrition and the loss of skeletal muscle mass, called sarcopenia, have a significant negative impact on the post-transplantation outcome, it is essential to provide adequate nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the necessary caloric intake. We herein discuss both bioelectrical impedance and the latest findings in the current perioperative nutritional interventions in liver transplant patients regarding synbiotics, micronutrients, branchedchain amino acid supplementation, the use of immune system modulating formulas, the fluid balance and the offering of nocturnal meals.

Hypoalbuminemia in patients with end-stage liver disease persists for weeks even after liver transplantation. Human albumin is widely used for volume replacement, to increase oncotic pressure, to improve organ function, and to promote wound healing. However, these practices are not evidence-based. We prospectively studied the clinical outcome of 40 patients following living related liver transplantation. Patients were randomized to an albumin group (n ϭ 20), where 20% human albumin was administered to maintain serum albumin level Ն3 g/dL, and a control group (n ϭ 20), where there was no correction for serum albumin. Hemodynamics and laboratory investigations, fluid administration, blood transfusion, and fluid balance were recorded during the first 5 days in the intensive care unit. Serum albumin level was significantly higher in the albumin group. Heart rate, blood pressure, central venous pressure, and cardiac output did not vary significantly between the groups. There was no significant difference in serum creatinine, creatinine clearance, bilirubin, ALT, AST, prothrombin time, and international normalized ratio between both groups. No significant difference between Tacrolimus level and dose required to maintain therapeutic concentration was noted between both groups. Postoperative course and complications did not vary significantly between both groups. In conclusion, postoperative albumin administration to a target serum albumin Ն3 g/dL does not have additional benefits for the postoperative course in patients scheduled for living related liver transplantation.

mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and in vivo and suggest the possible use of anti-SR-B1 antibodies as therapeutic agents.

Total parenteral nutrition is a life saving therapy for patients with chronic gastrointestinal failure, being an effective method for supplying energy and nutrients when oral or enteral feeding is impossible or contraindicated. Clinical epidemiological data indicate that total parenteral nutrition may be associated with a variety of problems. Herein we reviewed data on the gastroenterological tract regarding: (i) total parenteral nutrition-related hepatobiliary complications; and (ii) total parenteral nutrition-related intestinal complications. In the first group, complications may vary from mildly elevated liver enzyme values to steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis. In particular, total parenteral nutrition is considered to be an absolute risk factor for the development of biliary sludge and gallstones and is often associated with hepatic steatosis and intrahepatic cholestasis. In general, the incidence of total parenteral nutrition-related hepatobiliary complications has been reported to be very high, ranging from 20 to 75% in adults. All these hepatobiliary complications are more likely to occur after longterm total parenteral nutrition, but they seem to be less frequent, and/or less severe in patients who are also receiving oral feeding. In addition, end-stage liver disease has been described in approximately 15-20% of patients receiving prolonged total parenteral nutrition. Total parenteral nutrition-related intestinal complications have not yet been adequately defined and described. Epidemiological studies intended to define the incidence of these complications, are still ongoing. Recent papers confirm that in both animals and humans, total parenteral nutrition-related intestinal complications are induced by the lack of enteral stimulation and are characterised by changes in the structure and function of the gut. Preventive suggestions and therapies for both these gastroenterological complications are reviewed and reported in the present review.

To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis. Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients. Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Beca...

Non-alcoholic fatty liver disease is the clinical hepatic expression of metabolic syndrome. The prevalence of non-alcoholic fatty liver disease is around 20-30%, and with a rapid increase in the metabolic risk factors in the general population, non-alcoholic fatty liver disease has become the most common cause of liver disease worldwide. A fraction (20-30%) of non-alcoholic fatty liver disease patients develop a potentially progressive hepatic disorder, namely non-alcoholic steatohepatitis, leading to end-stage liver disease. The pathogenesis of non-alcoholic fatty liver disease is not entirely understood, and even if insulin resistance is a major pathogenetic key, many other factors are implicated in both liver fat accumulation and disease progression to non-alcoholic steatohepatitis. In this review we aim to examine the literature, principally concerning human non-alcoholic fatty liver disease pathogenesis, and to identify the newest, most promising clinical and basic research data. (S. Petta).

POSTERS However, the available information regarding its incidence and predictive factors is scarce. Aims: To assess frequency, clinical and microbiological findings and the existence of predictive factors of infection episodes during MARS therapy. Methods: Eighty-three patients received MARS therapy between January 2002 and September 2006. Clinical features (age, sex, indication of MARS therapy, concomitant immunosuppressive therapy or steroid use, previous recent infection, renal impairment), as well as characteristics of MARS procedure (number of sessions, use of antibiotic prophylaxis) and in hospital mortality were analyzed. Infection during MARS was defined as the appearance of culture proven infection or unequivocal clinical findings of infection from the first MARS session until 7 days after the last session. Results: The indication for MARS treatment was acute-on-chronic liver failure (ACLF) in 31 patients (37.3%), refractory pruritus in 16 cases (19.3%), fulminant hepatic failure in 19 patients (22.9%), post-liver transplantation distinction in 12 (14.4%) and other reasons in 5 cases (6%). Sixty-seven patients (80%) received antibiotic prophylaxis during MARS sessions. Seventeen patients (20.5%) had infection, only one of them without antibiotic prophylaxis. Four (23%) patients developed bacteraemia, 5 (29.4%) respiratory infections, 3 (17.5%) urinary tract infections, 1 (5.9%) spontaneous bacterial peritonitis and 4 (23%) had other locations. Although gram positive isolates were most frequently found (29.4%), gram negative (1 1.8%), anaerobic (5.9%) and fungal isolates (17.4%) were

Malnutrition has increasingly been acknowledged as an important prognostic factor which can influence the clinical outcome of patients suffering from end-stage liver disease (ESLD). Despite the fact that malnutrition is not included in the Child-Pugh classification, its presence should alert clinicians to the same extent as do other complications, such as ascites and hepatic encephalopathy. The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill-balanced metabolic state are multiple and they intertwine. Inadequate offer of nutrients, the hypermetabolic state in cirrhosis, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are the main reasons that disrupt the metabolic balance in ESLD. Identifying patients that are approaching the state of malnutrition by simple and easily applied methods is necessary in order to provide nutritional support to those that need it most. According to the European Society for Clinical Nutrition and Metabolism, simple bedside methods such as Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of cirrhotic patients. Correcting the nutrient deficit of the affected patients is mandatory. Avoidance of alcohol and excess fat and ingestion of 4-6 meals/day containing carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral feeding and/or use of special formulae such as branched-chain amino acid-enriched nutrient mixtures are often recommended. Enteral nutrition improves nutritional status and liver function, reduces complications, prolongs survival and is therefore indicated.

Introduction Orthotopic liver transplantation has become a routinely applied therapy for an expanding group of patients with end-stage liver disease. Shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. There is current debate about the regulation and results of liver transplantation using marginal grafts. Methods The study included data of all patients who received deceased donor liver grafts between March 2007 to December 2011. Patients with acute liver failure, living donor transplantation, split liver transplantation, and retransplantation were excluded. Early allograft dysfunction, primary nonfunction, patient survival, and incidence of surgical complications were measured. Results A total of 33 patients were enrolled in this study. There were 20 marginal and 13 nonmarginal grafts. The two groups were well matched regarding age, sex and indication of liver transplantation, model for end-stage liver disease score, technique of transplant, requirement of vascular reconstruction, warm ischemia time, blood loss, mean operative time, etc. In our study, posttransplant peak level of liver enzymes, international normalization ratio, and bilirubin were not statistically significant in the marginal and nonmarginal group. Wound infection occurred in 10 % of marginal compared with 7.7 % of nonmarginal graft recipients (p>0.05). In the marginal group, the incidences of vascular complications, hepatic artery thrombosis (four), and portal vein thrombosis (one) were not statistically significant compared to the nonmarginal group. Acute rejection was observed in a total of seven patients (21.2 %)-five (25 %) in the marginal group and two (15.4 %) in the nonmarginal graft recipients. Primary nonfunction occurred in three (9.1 %) patients-two (10 %) in the marginal and one (7.7 %) in the nonmarginal group. Average patient survival for the whole group was 91 % at 1 week, 87.8 % at 3 months, and 84.8 % at 6 months. Conclusion Because organ scarcity persists, additional pressure will build to use a greater proportion of the existing donor pool. The study, although small, clearly indicates that marginal livers can assure a normal early functional recovery after transplantation.

Orthotropic liver transplantation is the only established treatment for end-stage liver diseases. Utilization of hepatocyte transplantation and bio-artificial liver devices as alternative therapeutic approaches requires an unlimited source of hepatocytes. Stem cells, especially embryonic stem cells, possessing the ability to produce functional hepatocytes for clinical applications and drug development, may provide the answer to this problem. New discoveries in the mechanisms of liver development and the emergence of induced pluripotent stem cells in 2006 have provided novel insights into hepatocyte differentiation and the use of stem cells for therapeutic applications. This review is aimed towards providing scientists and physicians with the latest advancements in this rapidly progressing field.

Hepatitis C virus (HCV) is the main cause of severe liver disease, including hepatocellular carcinoma, cirrhosis and end stage liver disease. In Pakistan most of HCV positive patients have history of facial/armpit shaving from barbers. 79% of barbers are rubbing Potash Alum stone on facial shaving cuts. Dark blood spots are analyzed on Potash Alum stones being used at different barber shops. The aim of the study was to check the viability of hepatitis C virus on potash alum stone being used at barber shops. Blood samples from HCV positive patients were taken and treated with 0.1, 0.2, 0.3, 0.4 and 0.5 molar concentrations of Potash Alum for different periods of time. Blood was centrifuged to isolate the serum; HCV RNA was extracted from serum and subjected to first strand synthesis and PCR. PCR fragments were confirmed by sequencing. PCR amplification was observed in all the samples, treated with different concentrations of Potash Alum, indicated that the virus remains alive on Pota...

Core tip: Hepatitis B viral (HBV) infection continues to be a major health problem world-wide. Recurrence of WJG 20 th Anniversary Special Issues (9): Hepatitis B virus TOPIC HIGHLIGHT HBV following liver transplantation was a major problem in the 1980's-1990's, which led most insurers to refuse to cover costs of such transplants. This changed dramatically following the landmark demonstration that high-dose hepatitis B immune globulin (HBIG) could prevent recurrent infection. Recently, highly effective inhibitors of the HBV polymerase, with high barrier to resistance (entecavir, tenofovir) have become available, and they promise to decrease the need for HBIG and the costs and complexity of preventing recurrent HBV after liver transplantation.

The psychometric hepatic encephalopathy score (PHES), which includes 5 psychometric tests, is a standard for the diagnosis of minimal hepatic encephalopathy (HE). We investigated whether a simplified PHES (SPHES) is as useful as the whole PHES. METHODS: The PHES was determined for 79 cirrhotic patients (the training group), who were followed up for the development of overt HE. Backward logistic regression was performed by eliminating stepwise variables-removal did not impair regression. A separate series of 65 patients was used as a validation group. RE-SULTS: The PHES was abnormal in 45 patients. The SPHES, determined from the digit symbol, serial dotting, and line tracing tests, did not differ significantly from the full PHES; 24 of the 79 patients developed overt HE. The likelihood of developing overt HE was higher among patients with an abnormal PHES (log-rank P ϭ .003) or SPHES (P ϭ .004). By using Cox regression and model for end-stage liver disease scores to analyze data from patients with previous HE and transjugular intrahepatic portosystemic shunts, PHES (relative risk, 4.16; P ϭ .003) and SPHES (relative risk, 3.70; P ϭ .004) were the only variables associated with the development of overt HE. The accuracy of the SPHES was confirmed in the validation group.

Parenteral nutrition-associated liver disease (PNALD) is the most devastating complication of long-term parenteral nutrition therapy. Because its progression is typically insidious and its long-term consequences are generally underappreciated, PNALD is often recognized too late, when liver injury is irreversible. When end-stage liver disease (ESLD) develops in these patients, most potential interventions are futile and transplantation of both an intestine and a liver becomes the only viable option, despite the relatively poor outcomes associated with this combined procedure. Although likely multifactorial in origin, the etiology of PNALD is poorly understood. Early clinical intervention with a combination of nutritional, medical, hormonal, and surgical therapies can be effective in preventing liver disease progression. If these interventions fail, intestinal transplantation should be performed expeditiously before development of ESLD mandates simultaneous inclusion of a liver graft as well. (HEPATOLOGY 2006;43:9-19.)

Little is known about the safety of pediatric cardiac surgery in children with end-stage liver disease. We reviewed our experience with 4 patients with biliary atresia or Alagille's syndrome who underwent repair of ventricular septal defect and tricuspid regurgitation, atrioventricular canal, subaortic stenosis, or supravalvular aortic stenosis. One patient died on postoperative day 2. All other patients survived to discharge. At follow-up, 1 patient died at home awaiting liver transplantation and the remaining patients are doing well. One patient received a successful liver transplant. Pediatric cardiac surgery in children with end-stage liver disease can be done safely, albeit with a higher mortality.

Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence. Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence. Twenty-five patients (17 yogurt, 8 no Rx; 84% Ch...

OBJECTIVE: To analyze the impact of model for end-stage liver disease (MELD) allocation policy on survival outcomes after liver transplantation (LT). INTRODUCTION: Considering that an ideal system of grafts allocation should also ensure improved survival after transplantation, changes in allocation policies need to be evaluated in different contexts as an evolutionary process. METHODS: A retrospective cohort study was carried out among patients who underwent LT at the University of Pernambuco. Two groups of patients transplanted before and after the MELD allocation policy implementation were identified and compared using early postoperative mortality and post-LT survival as end-points. RESULTS: Overall, early postoperative mortality did not significantly differ between cohorts (16.43% vs. 8.14%; p = 0.112). Although at 6 and 36-months the difference between pre-vs. post-MELD survival was only marginally significant (p = 0.066 and p = 0.063; respectively), better short, medium and long-term post-LT survival were observed in the post-MELD period. Subgroups analysis showed special benefits to patients categorized as nonhepatocellular carcinoma (non-HCC) and moderate risk, as determined by MELD score (15-20). DISCUSSION: This study ensured a more robust estimate of how the MELD policy affected post-LT survival outcomes in Brazil and was the first to show significantly better survival after this new policy was implemented. Additionally, we explored some potential reasons for our divergent survival outcomes. CONCLUSION: Better survival outcomes were observed in this study after implementation of the MELD criterion, particularly amongst patients categorized as non-HCC and moderate risk by MELD scoring. Governmental involvement in organ transplantation was possibly the main reason for improved survival.

Bei ausgewählten Indikationen wurden exzellente Ergebnisse nach Lebertransplantation berichtet. Die Ergebnisse in unserem Zentrum wurden über 23 Jahre mit 2114 konsekutiven Lebertransplantationen in 1773 Patienten untersucht (Epochen I–III jeweils 5,5 Jahre, Epoche IV 6,5 Jahre). Nach 20 Jahren erreichte das Gesamtüberleben 29,8%. Die häufigsten führenden Todesursachen waren Infektionen unterschiedlicher Genese (30%), Tumorrezidive (14,2%) und Pneumonie (8,4%). Die häufigsten führenden Ursachen für den Transplantatverlust waren Infektionen unterschiedlicher Genese (19,6%), initiale Nichtfunktion des Transplantates (14,6%) und Tumorrezidive (9,6%). Das Patientenüberleben und das Transplantatüberleben waren beide signifikant besser nach primärer Transplantation als nach erster Retransplantation (p Liver transplantation has been reported to reach excellent results for selected indications. We analysed the results of liver transplantation in our centre over a period of 23 years, with a total of 2,114 consecutive liver transplants in 1,773 patients (eras I–III 5.5 years each, era IV 6.5 years). Overall 20-year survival after liver transplantation was 29.8%. The most frequent leading causes of death were infections of various origins (30%), tumour recurrence (14.2%), and pneumonia (8.4%). The most frequent leading causes for graft loss were infection of various origins (19.6%), initial nonfunction of the graft (14.6%), and tumour recurrence (9.6%). Both long-term patient and graft survival were significantly better after primary liver transplantation than after first retransplantation (P

Background Hepatorenal syndrome (HRS) is the functional renal failure associated with advanced cirrhosis and has also been described in fulminant hepatic failure. Without liver transplantation its prognosis is dismal. Our study included patients with type 1 HRS associated with cirrhosis, who were not liver transplant candidates. Aim To identify variables associated with improved survival. Methods Sixty-eight patients fulfilled the revised Ascites Club Criteria for type 1 HRS. None of them was suitable for liver transplantation. All the patients were treated with combinations of: albumin, midodrine and octreotide, pressors, and hemodialysis. Results Median survival was 13 days for the whole group. Survival varied with the end-stage liver disease (ESLD) etiology: autoimmune, 49 days, cardiac cirrhosis, 22 days, idiopathic, 15.5 days, viral, 15 days, hepatitis C and alcohol, 14.5 days, alcohol 8 days, and neoplasia 4 days (p = 0.048). Survival of HRS associated with alcoholic liver disease versus other etiologies was not statistically significant (p = 0.1). Increased serum creatinine (p = 0.02) and urinary sodium 6-10 mEq/l (p = 0.027) at the initiation of therapy were prognostic factors for mortality. HRS treatment modalities (p = 0.73), use of dialysis (p = 0.56), dialysis modality (p = 0.35), use of vasopressors (p = 0.26), pre-existing renal disease (p = 0.49), gender (p = 0.90), and age (p = 0.57) were not associated with survival. Conclusions We report for the first time ESLD etiology as a prognostic factor for survival. The renal function (expressed as serum creatinine) and urinary Na (\5 mEq/l) at the time of diagnosis were found to be associated with survival, suggesting that early treatment might increase survival.

Background. Recently there has been great concern about the quality of life and health of liver transplant patients (LTP). These patients often present with metabolic disorders, which can improve with regular physical exercise. The aim of this study was to investigate the effect of a physical exercise program on the functional capacity of LTP. Method. The distance walked in the 6-minute walk test and the resting energy expenditure (REE) were evaluated in 15 subjects who regularly attend the outpatient Bias Fortes Clinic at Universidade Federal de Minas Gerais. The patients were divided into 2 groups, the Exercise Group (EG) (6 men and 3 women; 52 AE 15 years old, BMI 22.4 AE 4.0 kg/m 2 ) performed 24 sessions of continuous 30 min treadmill exercise. Intensity of exercise was increased from 50%e70% of the maximum heart rate over the training period. A group of 3 men and 3 women (39 AE 15 years, BMI 24.5 AE 4.4 kg/m 2 ) served as controls (CG). Results. After undergoing exercise training, patients in the EG showed a 19.4% increase in the distance walked (pre ¼ 453.6 AE 128.0 m and post ¼ 582.5 AE 90.1 m). Also, there was an increase in their REE (pre ¼ 1,060.0 AE 194.2 kcal and post ¼ 1,375.0 AE 258.6 kcal) (P < .05) indicating an increase in their exercise capacity and metabolic improvements. There were no differences in the distance walked (pre ¼ 516.5 AE 62.0 m and post ¼ 517.7 AE 71.9 m) and REE (pre ¼ 1,393.0 AE 213.3 kcal to post ¼ 1,465.0 AE 170.3 kcal) (P > .05) for CG. Our results are in agreement with previous studies. Conclusions. We conclude that the exercise program promoted significant improvements in functional capacity. These findings have positive implications for the control of metabolic diseases, which are common in patients after liver transplantation.

Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of

Sclerosing cholangitis can be idiopathic (primary) or secondary to an identifiable cause. Irrespective of cause, sclerosing cholangitis usually progresses to end-stage liver disease and warrants orthotopic liver transplantation. Recent studies provide new insights into the etiopathogenesis, natural history, diagnosis, and management of these different entities.

The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver disease. Embryonic stem cells can be readily differentiated into hepatocytes, and their transplantation into animals has improved liver function in the absence of teratoma formation: their use in bioartificial liver support is an obvious application. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted foetal or adult hepatocytes have proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells is clearly vital for survival in many cases of acute liver failure, but surprisingly little progress has been made with these cells in terms of transplantation. Finally there is the controversial subject of autologous bone marrow, and while the contribution of these indigenous cells to liver turnover seems at best, trivial, results from a small number of phase 1 studies of transplantation of bone marrow to cirrhotic patients have been moderately encouraging.

Chronic hepatitis B virus (HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation (LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B (CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins (HBIG) during the 1990s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance (e.g. , entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors (with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

There are several issues to be considered to reduce the risk of rejection and minimize side effects associated with liver cell transplantation in chronic liver diseases. The source and the condition of stem cell proliferation and differentiation ex vivo and the transplantation protocols are important safety considerations for cell based therapy. The biochemical and molecular markers are important tools for safety evaluation of different processes of cell expansion and transplantation. Studies show that hepatocytes differentiated from adult and embryonic stem cells exhibit biochemical and metabolic properties resembling mature hepatocytes. Therefore these assays can help to assess the biological and metabolic performance of hepatocytes and progenitor stem cells. The assays also help in testing the contribution of transplanted hepatocytes in improving the repair and function of damaged liver in the recipient. Here we review the biochemical and metabolic markers, which are implicated in evaluation of safety issues of stem cells used for therapeutic purposes in chronic liver diseases and regeneration of damaged liver. We also highlight application of biochemical tests for assessment of liver cell transplantation.

Background. Regadenoson is a selective A 2A receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined.

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3year patient survival. D-MELD cutoff predictive of 5year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Purpose To evaluate whether the WHOQOL-BREF measures the QOL construct in the same way across nations. Methods Students from Flanders, Belgium and Iran completed the WHOQOL-BREF as part of a larger Quality of Life questionnaire. Their responses were compared using a multi-group confirmatory factor analysis. Results In general, the QOL construct appears rather similar in both cultures; however, participants from both countries seem to respond differently to particular items of the WHOQOL-BREF. Especially for the physical and psychological domain, this is problematic, because none of their indicators works in the same way across samples. Conclusions Notwithstanding some limitations of this study, it must be concluded that the WHOQOL-BREF should only be used with great caution in cross-national comparisons.

Concomitant abdominal aortic aneurysms and cirrhosis that need surgical attention are rare. Currently there are no guidelines with regards to the appropriate timing of the repair of these aneurysms and transplantation. In addition it also raises the issue of which procedure takes precedence. With the advent of endovascular repairs, this issue was resolved with relative ease, by doing the orthotopic liver transplantation (OLT) first and subsequent endovascular stenting on post-operative day 7 during the same hospitalization. This is the first case report of stenting an abdominal aortic aneurysm (AAA) in a liver transplant recipient. The rationale for the OLT and then AAA repair are discussed and formal guidelines are offered.

Bei ausgewählten Indikationen wurden exzellente Ergebnisse nach Lebertransplantation berichtet. Die Ergebnisse in unserem Zentrum wurden über 23 Jahre mit 2114 konsekutiven Lebertransplantationen in 1773 Patienten untersucht (Epochen I–III jeweils 5,5 Jahre, Epoche IV 6,5 Jahre). Nach 20 Jahren erreichte das Gesamtüberleben 29,8%. Die häufigsten führenden Todesursachen waren Infektionen unterschiedlicher Genese (30%), Tumorrezidive (14,2%) und Pneumonie (8,4%). Die häufigsten führenden Ursachen für den Transplantatverlust waren Infektionen unterschiedlicher Genese (19,6%), initiale Nichtfunktion des Transplantates (14,6%) und Tumorrezidive (9,6%). Das Patientenüberleben und das Transplantatüberleben waren beide signifikant besser nach primärer Transplantation als nach erster Retransplantation (p Liver transplantation has been reported to reach excellent results for selected indications. We analysed the results of liver transplantation in our centre over a period of 23 years, with a total of 2,114 consecutive liver transplants in 1,773 patients (eras I–III 5.5 years each, era IV 6.5 years). Overall 20-year survival after liver transplantation was 29.8%. The most frequent leading causes of death were infections of various origins (30%), tumour recurrence (14.2%), and pneumonia (8.4%). The most frequent leading causes for graft loss were infection of various origins (19.6%), initial nonfunction of the graft (14.6%), and tumour recurrence (9.6%). Both long-term patient and graft survival were significantly better after primary liver transplantation than after first retransplantation (P