List For Liver Transplantation Research Articles

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

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

Large regenerative nodules in a patient with Budd-Chiari syndrome after TIPS positioning while on the liver transplantation list diagnosed by Gd-EOB-DTPA MRI

Large regenerative nodules (LRNs) are hyperplastic benign nodules most commonly associated with Budd-Chiari syndrome (BCS), caused by outflow obstruction of the hepatic veins or vena cava. To our knowledge, no cases of LRNs arising in BCS after transjugular intrahepatic portosystemic shunt (TIPS) positioning and detected by Gd-EOB-DTPA MRI have been reported in the literature. A 58-year-old woman with BCS, on the liver transplantation (LT) list, underwent a follow-up enhanced MRI. Two years earlier, a TIPS had been placed. In 2008, recurrent hepaticoencephalopathy resistant to medical treatment fulfilled the LT criteria for BCS treated with TIPS and the patient was therefore added to the LT list. CT performed before TIPS had not detected any hepatic lesions. CT performed six months after TIPS showed its complete patency but documented two indeterminate hypervascular liver lesions. MRI performed with Gd-EOB-DTPA revealed additional hypervascular lesions with uptake and retention of the medium in the hepatobiliary phase, thus reflecting a benign behavior of hepatocellular composition. These MRI features were related to LRNs as confirmed by histopathologic analysis. Gd-EOB-DTPA-enhanced MRI is potentially superior to standard imaging using gadolinium chelates or spiral CT, especially for the differential diagnosis of hypervascular lesions. Gd-EOB-DTPA MRI may become the imaging method of choice for evaluating LT list patients with BCS after TIPS placement.

Cell-based therapeutics for liver disorders

Due to a lack of adequate liver donors and post-surgical complications, researchers propose that cell therapy should be an alternative treatment for patients with end-stage liver diseases. We performed a literature review on cell-based therapy for liver disorders. Due to growing numbers of patients on waiting lists for liver transplantation, a substitute treatment strategy is needed for our patients. Cell therapy can save patients who are in life-threatening situations, enabling them to have more time and increase their chances of survival. Pluripotent stem cells can be a good resource for cell-based therapy after the establishment of efficient differentiation protocols in addition to the settlement of ethical and immunological issues. Cell-based therapy will be applicable after the approval of its efficiency via animal model studies. Transplanted cells cannot integrate into the recipient liver and lose their functionality after a limited time. The rate of homing and transdifferentiation of transplanted cells into hepatocytes is scant. Application of autologous bone marrow mononuclear cells (MNCs), hematopoietic and mesenchymal stem cells (HSCs and MSCs) has improved the general conditions of certain patients. Although this improvement is temporary, new studies have focused on increasing their performance. TIMELY AREAS FOR DEVELOPING RESEARCH: The safety, feasibility and efficacy of applying MNCs, HSCs and MSCs in liver disorders have been proven in clinical trials. Patient-specific cell therapy after the production of induced pluripotent stem cells and new discoveries in somatic cell conversion during transdifferentiation are promising insights.

The effect of changes of model for end-stage liver disease score during waiting time on post-liver transplant mortality

Model for End-Stage Liver Disease (MELD) score is found to be a robust predictor of mortality while on waiting list for liver transplantation. However, studies have shown inconsistent results for transplant MELD as a predictor of posttransplant mortality. To find whether utilization of MELD at listing, at transplant, or Δ MELD while waiting can predict outcome at a national transplant center, which is not part of an organ sharing network. Retrospective analysis of patients listed for liver transplantation at the New Zealand Liver Transplant Unit (NZLTU) with calculation of MELD score at the time of listing and at transplant with/without adjustment points for hepatocellular carcinoma (HCC). Between 1998 and 2005, 264 adult patients were listed for liver transplantation. Median age at transplant was 49years (range 16-70) and 65% were male. The most common etiology was viral hepatitis (50%). A total of 48 patients (20%) had known HCC. MELD scores (adjusted and nonadjusted) at listing and at transplantation were similar across all primary liver diseases (P=0.88, 0.93, respectively). Adjusted MELD scores were significantly higher in patients listed for HCC compared to those without HCC (P<0.001; hazard ratio 1.33; 95% confidence interval=1.21-1.46). MELD scores at transplant did not correlate with either 3 or 12months mortality (P=0.336, 0.228, respectively). This finding was consistent whether the change of MELD during waiting time was >1 point or less (P=0.67). Waiting time does not appear to influence posttransplant survival (P=0.75). In a country with a single transplant center and organ retrieval organization, the addition of MELD score to current minimal listing criteria does not improve prioritization of patients on the waiting list or predict posttransplant survival. Also, adjusting MELD score for HCC would unfairly disadvantage patients listed without HCC.

FATE OF PATIENTS WITH LATE-DETECTED HEPATITIS C INFECTION - CASE REPORTS

Chronic hepatitis C virus infection represents an insidious disease that is often detected with signs of liver cirrhosis or hepatocellular carcinoma. It is practicaly impossible to achieve a significant therapeutic progress in these patients without performing a liver transplantation. However, due to underdeveloped program of organ donations, this kind of intervention, as the last helpful procedure, is often not realized. This study presents three patients (out of 121 treated patients) followed during a two-year period. The patients had been initially registered when the stage of their disease became severe: liver failure with signs of decompensation. Antiviral therapy (pegylated interferon and ribavirin) in these patients have no use, hence only a corrective therapy is administered. Pathohistological findings in two patients revealed hepatocellular carcinoma, and in one case lethal outcome was the result of severe hepatic decompensation, hepatopulmonary and hepatorenal syndromes, as well as developed cardiopulmonary failure. Lethal outcome occurred in the period of 2 to 14 months after the first visit to a doctor. One patient was on the list for liver transplantation; however, surgery was not performed and soon after a fatal outcome ensued. Acta Medica Medianae 2011;50(2):49-52.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease

Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

Bridge Treatments for HCC in the Waiting List for Liver Transplantation

During the past years, several therapeutic procedures have been proposed as bridging treatments in patients with hepatocellular carcinoma waiting for liver transplantation. Resective surgery, transarterial chemoembolization, radiofrequency thermal ablation and percutaneous ethanol injection are the most experienced, with the aim to decrease the rate of drop-out from LT waiting list, and the risk of HCC recurrence after transplant. Indeed, for patients within the criteria, a time on waiting list exceeding 6-12 months is a known risk factor of tumor progression and drop out. For this reason, the application of bridging treatments in these patients might be reasonable and several studies in recent years have documented their usefulness to control tumor progression before the transplant. However, the favourable impact of these treatments on post-transplant patients' survival is still under investigation and the available studies provide controversial results. Bridging therapies have also been used for the downstaging of tumors exceeding the conventional Milan criteria. Some recent data regarding multimodal sequential therapies seem to report promising results in terms of overall and disease-free survival of treated patients attaining effective downstaging before transplant.

FDA evaluation of hepatotoxicity related to tyrosine kinase inhibitors.

3106 Background: Tyrosine kinase inhibitors (TKIs) interfere with several critical signal transduction pathways in cancer. Nine TKIs have been FDA approved to treat a variety of malignancies. TKIs have been associated with severe liver injury (SLI). Whether this liver injury is a class effect, or specific to certain TKIs is being investigated. Methods: Analyses included evaluation of postmarketing reports of SLI associated with 9 TKIs (imatinib, dasatinib, nilotinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib, and pazopanib) from FDA’s Adverse Event Reporting System (AERS) and literature review. SLI is defined as acute liver injury (elevated LFTs, bilirubinemia, or jaundice) in combination with one of the following events: death, liver transplantation or placement on liver transplant list, hepatic encephalopathy, coagulopathy or renal impairment. Clinical toxicity data, demographics, drug metabolism, laboratory, pharmacokinetic and exposure data were reviewed from new drug application (NDA) sub...

Assessing patients before and after a liver transplant

Practice NursingVol. 22, No. 5 Clinical Chronic DiseaseAssessing patients before and after a liver transplantMichelle ClaytonMichelle ClaytonSearch for more papers by this authorMichelle ClaytonPublished Online:29 Sep 2013https://doi.org/10.12968/pnur.2011.22.5.236AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleReferencesBritish Association of Dermatologists (2010) Information about skin cancer for patients with an organ transplant. http://tiny.cc/4v0s0 (accessed 12 April 2011) Google ScholarDepartment of Health (2007) Immunisation Against Infectious Disease: ‘The Green Book’. http://tiny.cc/79n9z (accessed 12 April 2011) Google ScholarDepartment of Health (2008) Organs for Transplant: A Report from the Organ Donation Taskforce. The Stationery Office, London Google ScholarHamlin S, Leaper J (2009) Nutrition in Liver Disease. In: Sargent S, ed Liver Diseases: An Essential Guide for Nurses and Health Care Professionals. Wiley–Blackwell, London Crossref, Google ScholarHoulston C, O’Neal H (2009) Hepatic encephalopathy. In: Sargent S, ed Liver Diseases: An Essential Guide for Nurses and Health Care Professionals Wiley–Blackwell, London Crossref, Google ScholarHumar A, Matas A (2001) Immunosuppression: Use in Transplantation. Encyclopedia of Life Sciences,.John Wiley andSons Ltd Crossref, Google ScholarJoint Formulary Committee (2011) British National Formulary 61. March. Pharmaceutical Press Google ScholarKamath P, Wiesner R, Malinchoc Met al. (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33: 464–70 Crossref, Google ScholarKrige J, Beckingham I (2001) ABC of diseases of liver, pancreas, and biliary system. Portal hypertension–2. Ascites, encephalopathy, and other conditions. BMJ 322(7283): 416–41 Crossref, Google ScholarLiver Advisory Group (2005) UK Liver Transplant Group Recommendations for Liver Transplant Assessment in the Context of Alcohol-related Liver Disease. http://tiny.cc/bfjz3 (accessed 6 April 2011) Google ScholarLiver Advisory Group (2007) UK Liver Transplant Group Recommendations for Liver Transplant Assessment in the Context of Illicit Drug Use. http://tiny.cc/x5mhj (accessed 6 April 2011) Google ScholarMarchetti P (2005) New–onset diabetes after liver transplantation: from pathogenesis to management. Liver Transpl 11(6): 612–20 Crossref, Google ScholarMoore K, Aithal G (2006) Guidelines on the management of ascites in cirrhosis. Gut 55(Suppl 6): vi1–12 Crossref, Google ScholarMurphy C, Counter C (2009) Potential Donor Audit. Summary Report for the 24-month period 1 April 2007–31 March 2009. http://tiny.cc/y13qj (accessed 12 April 2011) Google ScholarNeuberger J, Gimson A, Davies Met al. (2008) Selection of patients for liver transplantation and allocation of donated livers in the UK. Gut 57(2): 252–7 Crossref, Google ScholarNHS Blood and Transplant (2011a) Activity report 2009–10 Section 9 Survival rates following transplantation. http://www.organdonation.nhs.uk/ukt/statistics/transplant_activity_report/transplant_activity_report.jsp (accessed 11th April 2011) Google ScholarNHS Blood and Transplant (2011b) Liver Activity 2010–2011. (in press Google ScholarNHS Blood and Transplant (2011c) Liver transplant list and new registration in the UK. 1 April 2010–31 March 2011. (in press) Google ScholarNHS Blood and Transplant (2011d) Median waiting time to liver transplant in the UK 1 April 2007–31 March 2010. (in press) Google ScholarRossetto A, Bitetto D, Bresadola Vet al. (2010) Cardiovascular risk factors and immunosuppressive regimen after liver transplantation. Transplantation Proc 42(7): 2576–8 Crossref, Google ScholarSargent S (2009) Liver Diseases: An Essential Guide for Nurses and Healthcare Professionals. Wiley-Blackwell, Oxford Crossref, Google ScholarWatt KDS, Charlton MR (2010) Metabolic syndrome and liver transplantation: A review and guide to management. J Hepatol 53(1): 199–206 Crossref, Google ScholarWatt KDS, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR (2010) Evolution of causes and risk factors for mortality post-liver transplant: Results of the NIDDK long-term follow-up study. American Journal of Transplantation 10(6): 1420–7 Crossref, Google Scholar FiguresReferencesRelatedDetailsCited byA systems-based approach to patient care after liver transplantationJournal of the American Academy of Physician Assistants, Vol. 31, No. 1Caracterização sociodemográfica e clínica de candidatos a transplante de fígadoActa Paulista de Enfermagem, Vol. 29, No. 2 1 May 2011Volume 22Issue 5ISSN (print): 0964-9271ISSN (online): 2052-2940 Metrics History Received 12 April 2011 Accepted 16 April 2011 Published online 29 September 2013 Published in print 1 May 2011 Information© MA Healthcare LimitedKeywordsliver transplantationassesmmentimmunosuppressive drugsAcknowledgmentsFigure 1 is reproduced with permission of Wiley-Blackwell.PDF download

Validation of 20-Meter Corridor for the 6-Minute Walk Test in Men on Liver Transplantation Waiting List

Background Guidelines established by the American Thoracic Society recommend the use of corridors 30 m in length for the 6-minute walk test (6MWT). However, not all institutions have such long corridors, which hinders or prevents 6MWT performance and use of its benefits. Objective To compare the distances walked by male patients with cirrhosis on the liver transplantation waiting list, we performed 6MWT on corridors 20 and 30 m long. Methods This prospective study included 10 patients on the waiting list for liver transplantation. They underwent 2 walk tests: the first test in a 20 m corridor and the second in a 30 m corridor. We assessed physiologic variables (heart rate, oxygen saturation, arterial blood pressure) and the subjective sensation of dyspnea at rest at 6 and 9 minutes after each walk. Statistical analysis was performed using the Wilcoxon test. Results Data are expressed as mean ± sd. Patient age was 59 ± 10 years. The distances walked by the patients were shorter than those predicted for their age and gender (586 ± 45 m) in both tests, no significant difference was observed between the first and the second 6MWT (437 ± 101 m vs 465 ± 80 m; P = .131) or among the physiologic variables. Conclusion We concluded that a 20 m corridor can be used safely and effectively as an alternative to 30 m for the 6MWT for male patients with cirrhosis on the liver transplantation waiting list.

Preoperative Natriuretic Peptide-B Values and Ascites in Male Liver Transplant Recipients

Plasma preoperative values of natriuretic B peptide (pro-BNP) were correlated with ascites in men experiencing hepatic cirrhosis due to different etiologies on the active waiting list for liver transplantation. The study was performed in 54 male recipients of a liver transplant. Written informed consent was obtained from the patients or their relatives, and the study protocol was approved by our local Clinical Research (Ethics) Committee. Male patients were classified into two groups: group 1 included patients with alcoholic hepatic cirrhosis ( n = 30) distributed as 19 men with no ascites, four with nonrefractory ascites, and seven with refractory ascites; group 2 included cases of viral hepatitis cirrhosis ( n = 24) distributed as 13 men with no ascites, nine with non-refractory ascites, and two with refractory ascites. A group of six healthy male volunteers was used to establish normal (basal) values of pro-BNP and left auricular diameter (LAD). Pro-BNP values were determined in plasma samples by an electrochemiluminiscence immunoassay. Pro-BNP plasma levels in patients with alcoholic cirrhosis were threefold greater among patients with no ascites or no refractory ascites compared with healthy men, whereas pro-BNP values were fivefold enhanced among alcoholic patients with refractory ascites. The viral hepatitis cirrhosis group showed pro-BNP plasma values 1.5-fold enhanced in men with no ascites, whereas pro-BNP reached fivefold with either nonrefractory or refractory ascites. The enhanced pro-BNP plasma levels indicated advanced hepatic degradation, seemingly related to the presence of refractory ascites associated with cirrhosis.

Mortality on the Waiting List for Liver Transplantation: Management and Prioritization Criteria

The excellent outcomes of liver transplantation (OLT) have increased its demand and the size of the waiting list, resulting in a substantial mortality rate before OLT, which is a treatment failure owing to disease development. We have reviewed the medical literature on this theme, focusing on prioritization methods.

Testing Beneficial Therapy in Human Cirrhosis Using Animal Models of Cirrhosis

The study by Minuk and colleagues entitled “Daily Ciprofloxacin Treatment for Patients with Advanced Liver Disease Awaiting Liver Transplantation Reduces Hospitalizations” [1] tested the hypothesis that patients on the liver transplant list may benefit from antibiotics as a method of enhancing hepatic regeneration and improving liver function. The authors had previously shown in a rat model of acute and subacute liver failure that antibiotics improved survival [2, 3] and that antibiotics appeared to also improve survival in a model of chronic liver injury [4]. This benefit correlated in these animal models with improvement in markers of hepatic regeneration. In the current study, the authors asked whether the same benefit might be found in cirrhotic patients on the liver transplant waiting list. This single-site, prospective, randomized, double-blind study measured routine markers of hepatic function (albumin, bilirubin, and international normalized ratio for prothrombin time [INR]), markers of hepatic inflammation (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and clinical outcomes (hospitalizations, hepatic encephalopathy, etc.) after 1 or 3 months of treatment with placebo or ciprofloxacin 250–500 mg twice daily. Results showed no systematic benefit at 1 or 3 months in markers of hepatic function or inflammation, and a significant improvement in albumin at 1 month was not confirmed at 3 months. However, it should be noted that more precise measurements of hepatic function [5, 6] or markers of regeneration might have shown subclinical benefits that would have been encouraging for further studies. Potential benefits in hospitalizations and clinical outcomes were also assessed. There were fewer hospitalizations for hepatic encephalopathy among subjects receiving ciprofloxacin, but little benefit for other clinical outcomes. As the authors note, antibiotics are helpful in treating encephalopathy and in prophylaxis against spontaneous bacterial peritonitis [7–10]. The effect of antibiotics on improvement in survival among variceal bleeders has been profound [11]. Thus, the reduction in hospitalizations among patients receiving antibiotics in this study is not surprising, and hepatic regeneration is not required to explain this improvement. Thus, the benefits of antibiotics in animal models of acute and chronic liver injury were not confirmed in this clinical trial among patients with advanced cirrhosis on the liver transplant waiting list. Animal models have been very useful in the evaluation of the pathophysiology of portal hypertension, ascites and hepatic fibrosis [12–17]. Why was so little benefit observed when antibiotics were used in humans with cirrhosis as compared with animal models? The answer partially lies in the difference between changes in pathophysiology in animal models of acute liver injury and humans with cirrhosis, who have dense hepatic fibrosis that develops over long periods of time and resolves slowly when the insult is stopped [18, 19]. By contrast, animal models of cirrhosis generally require continued liver injury to produce cirrhosis, and fibrosis resolves rapidly if the insult is stopped [12–17]. Furthermore, there is often a complex interaction of factors contributing to hepatic injury that includes bacterial products such as endotoxin from the gut that may be less important in man [12–14]. Antibiotics markedly decrease injury in most animal models [12–14]. Therefore, study of the pathophysiology of liver injury and complications of liver disease in animal models has been very valuable, but the regression of liver fibrosis differs between humans and animals. Thus, findings in animal models must be confirmed in clinical settings, and we applaud the authors for testing their hypothesis in humans [1]. Unfortunately, this study shows that antibiotics do not enhance hepatic regeneration or improve clinical outcomes by means of regeneration in patients on the liver transplant list. According to several recent studies, there is no experimental model that completely reproduces human liver fibrosis [12–14]. Since there are contraindications to serial liver biopsies in humans with liver disease, studies of genetic and molecular aspects of liver injury and fibrosis should continue. An initial approach should involve exploration of the molecular mechanisms of liver fibrosis in different diseases [20]. This might elucidate areas of potential efficacy of ciprofloxacin and other fluoroquinolones. Ultimately, all benefits in animals must be confirmed by clinical trials in man.

Is estimated glomerular filtration rate superior to serum creatinine in predicting mortality on the waiting list for liver transplantation?

Serum creatinine is an important prognostic indicator in patients on the liver transplant waiting-list, being a component of the Model for End Stage Liver Disease (MELD) score. However, creatinine is influenced by age, gender and race, and in this role may disadvantage some individuals. The Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate (eGFR) takes into account these variables and may be a superior measure of renal function. Our aim was to examine whether the MDRD 4-variable, 5-variable and 6-variable eGFRs are superior to serum creatinine in predicting 3-month waiting-list mortality in patients with end-stage liver disease. This was a retrospective single-centre study of 427 adults listed for first liver transplantation. The median listing MDRD 4-variable, 5-variable and 6-variable eGFR was 69, 71 and 73 ml/min/1.73 m(2) , respectively. The median listing serum creatinine was 89 μm. MDRD 4-variable (P = 0.002), 5-variable (P < 0.001) and 6-variable eGFR (P < 0.001), and serum creatinine (P < 0.001), were all predictors of mortality on the transplant waiting-list. Of the three MDRD equations, the 6-variable eGFR was the better prognostic indicator. The substitution of 6-variable eGFR for serum creatinine did not improve the prognostic accuracy of the MELD (P = 0.825) and UK score for Patients with End-Stage Liver Disease (P = 0.781) scores. In conclusion the MDRD eGFR is comparable, but not superior to serum creatinine, in predicting death within 3 months of listing for liver transplantation.

617 RELATIONSHIP BETWEEN SMALL INTESTINAL BACTERIAL OVERGROWTH AND INTESTINAL PERMEABILITY IN CIRRHOSIS

s A.I.S.F. Annual Meeting (Rome, February 25th−26th, 2010) / Digestive and Liver Disease 42 Suppl. 1 (2010) S1–S51 S19 with normal spleen diameter (p 20 ppm or a rise by 12 ppm above baseline following glucose administration was considered as positive. IP was evaluated by the (51)Cr-EDTA permeability test. SIBO prevalence in LC was compared with healthy controls and correlated with LC severity and IP. Results: Twenty-nine out of 56 LC patients had SIBO vs 2 of the 48 healthy controls (51.8% vs 4%, p< 0.0001). SIBO prevalence correlated with the severity of LC (68.2% of Child C pts vs. 56.2% of Child B and 31.2% of Child A pts), with the presence of ascites (66% in ascitic pts vs. 27% in non-ascitic pts), and with a history of SBP (92% of patients with SBP vs. 48% of those without SBP). A significant correlation was found between presence of SIBO and altered IP: it was weak for Child A but significant for Child B and C pts (R = 0.07, NS; R = 0.35, p = 0.005; R = 0.29, p = 0.03, respectively). Conclusions: SIBO seems to have a higher prevalence in LC, correlates with LC severity and altered IP. This association suggests that SIBO may affect intestinal permeability of splancnic vessels and/or peritoneal membranes leading to SBP outbreak in LC. Future interventional studies are needed to confirm these preliminary data. T.N.13 PREDICTORS OF OUTCOME IN CIRRHOTICS ADMITTED TO INTENSIVE CARE UNIT (ICU); SURVIVORS EXHIBITED SIGNIFICANT RISE OF SERUM SODIUM LEVELS AND A FALL IN LACTATE LEVELS AT 48 HOURS M. Garcovich1,2, V. Vemala1, A. Davenport1, E. Dionigi1, S. Shaw1, B. Agarwal1, A.K. Burroughs1. Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK; Dipartimento di Medicina Interna, Universita Cattolica del Sacro Cuor, Rome, Italy Background: Critically ill cirrhotics admitted to ICU have poor prognosis. Factors known to portend worse outcome include mechanical ventilation, development of shock, renal failure and increasing number of organ failure. While a negative impact on mortality of low serum sodium level is observed in stable cirrhotics active on the waiting list for liver transplant, the impact of admission serum sodium and its changes during the course of an acute illness in these patients is not well known. Methods: We retrospective studied a cohort of cirrhotics admitted to ICU between 2005−08 at the Royal Free Hospital. Data were collected on demographic variables, aetiology of liver disease, liver-specific prognostic scores; Child–Turcotte–Pugh (CTP), Model for end-stage liver disease (MELD), United Kingdom model for end-stage liver disease (UKELD), acute physiological score and chronic health points (APACHE II) and sequential organ failure assessment score (SOFA). In addition, data were also collected for serum Na+ and Lactate levels at 0 (on admission) and at 48 hrs. Results: Currently 67 of 125 patients have been enrolled. 51/67 (76.1%) survived ICU. The non-survivors (16/67) had similar demographics as the survivors, had significantly higher mean MELD, UKELD, SOFA and APACHE II scores, and higher admission lactate. Total CTP score was not different between the groups but serum bilirubin level and prothrombin time were significantly higher in the non-survivors. Although the admission Na+ levels in survivors and non survivors were similar, a significant elevation was observed at 48 hrs in the survivors. The trend for serum lactate levels showed a similar pattern i.e., the survivors showed significant reductions at 48 hrs. Conclusions: The reasons for this observed rise in serum Na+ at 48 hrs in the survivors are not obvious. It may signify a better preserved water balance in patients with less severe underlying liver disease. T.N.14 COLLAGEN PROPORTIONATE AREA IN ASSESSING THE AMOUNT OF FIBROSIS IN CHRONIC LIVER DISEASE: DOES HIGH RESOLUTION COMPARED TO CONVENTIONAL IMAGE CAPTURING AND ANALYSIS ALTERS ITS RESULTS? L. Andreana1, G. Isgro1, M. Garcovich1, A. Hall2, F. Grillo2, A.P. Dhillon2, A.K. Burroughs1, T.V. Luong2. The Sheila Sherlock Liver Centre and University Dept. of Surgery, Royal Free Hospital, London, UK; Dept. of Histopathology, Royal Free Hospital,

Single-institution experience using transarterial chemoembolization (TACE) with carboplatinum (carbo) and doxorubicin in patients (pts) with hepatocellular carcimona (HCC) awaiting liver transplantation (LTx).

336 Background: LTx is the best treatment option for multinodular HCC and those with advanced liver dysfunction. Tumor progression occurs in 20-50% of pts on liver transplant list. TACE is increasingly used as locoregional therapy and as a bridge to LTx. We report here our single institutional experience with TACE using carbo and doxorubicin in pts with HCC awaiting LTx. Methods: Retrospective chart review was performed in all pts who had TACE between 2008 and June 2010. Our institutional protocol uses a fixed dose of carbo 300mg, doxorubicin 50mg, in 10ml of lipoidol solution. We analyzed pt demographics, etiologies of liver disease, Child-Pugh status, CLIP scores, size of tumor, alpha-fetoprotein (AFP), toxicity, length of stay, and transplantation statistics. Results: 32 pts (28 men) were treated with 39 TACE procedures. The median age was 57 (32-83). 28 of 32 had cirrhosis with Child's A/B/C 36/51/18% respectively. The major etiologies of cirrhosis were hepatitis C (HCV) 8, alcohol and HCV 19, alcohol 7; portal vein thrombosis in 8 pts. The median tumor size was 6.2 cm (range 2-12 cm) and 81% were multifocal CLIP score 0,1/2,&gt;3 were 5/62/38%. There were no mortality within 30 days of TACE procedure. The majority of the pts were discharged after 24 hr observation; 6 pts require readmissions within 30days. There was no systemic hematologic toxicity. 11 pts had elevated AFP at baseline and 6/11 (54%) had &gt;50 % reduction in AFP value. 11pts (34%) received Ltx; 3 pts came off the LTx list due to disease progression, 2 pts are still on transplant list, and 16pts not able to be listed. 42% of pts received sorafenib in addition to TACE. The median time from last TACE to LTx was 55 days and 4 pts received transplantation within 30days. Very good pathological treatment effect was observed in 8/11 explanted liver. Conclusions: Our regimen of TACE with carbo/doxorubicin appears to be a safe and tolerable approach for localized treatment as a bridge to liver transplantation. It has acceptable toxicity and is associated with good AFP and pathological responses. We plan to evaluate different baseline parameters for better pt selection. No significant financial relationships to disclose.

Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships

Mycophenolic acid (MPA) plasma concentrations were reported to be associated with a decrease in T-cell proliferation, and in both IL-2 α-chain (CD25) and transferin receptor (CD71) expression. The aim of this study was to confirm, quantify and model these PK/PD relationships. Full profiles of MPA plasma concentrations, T-cell proliferation, intracytoplasmic IL-2 and TNF-α expression, and both CD71 and CD25 expression were collected over the 12 h after dosing in 10 patients on the waiting list for liver transplantation. Data were analyzed using NONMEM ®. Both CD25 and CD71 expression and T cell proliferation clearly decreased (median of decrease from baseline 62%, 68% and 94%, respectively) with increasing MPA concentrations, in contrast to IL-2 and TNF-α expression. The CD25 and CD71 baseline expression ( E 0) and maximum effect ( E max) were correlated with the E 0 and E max values of T-cell proliferation ( r 2 = 0.509 and r 2 = 0.622, respectively). The CD25, CD71 expression and T-cell proliferation profiles were adequately fitted using a sigmoid inhibitory E max model. Low estimated values (≤2 mg/L) for 50% inhibitory MPA concentrations were obtained. This study confirmed a transient MPA concentration-dependent decrease in T-cells expressing CD25 and CD71 and a strong reduction of T-cell proliferation and showed that CD25 and CD71 expression was correlated with T-cell proliferation.

Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List

The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk. Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher's, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan-Meier estimators (log-rank test) were used to determine survival rates. Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078). Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients

Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child-Turcotte-Pugh (CTP) scores. Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy-three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c-statistics were calculated after stratification according to CTP and MELD score. For the mortality before transplantation, c-statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT's prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.

Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: Unique clinical and human leukocyte antigen associations

Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic, and African American PSC patients listed for liver transplantation (LT). Population-stratified demographic, clinical, and HLA data from 6767 LT registrants of the United Network for Organ Sharing who had a diagnosis of PSC (4.7% of the registrants) were compared to data from registrants with other diagnoses. Compared to European Americans and Hispanics, African Americans were significantly younger (46.6 ± 13.7, 42.3 ± 15.9, and 39.7 ± 13.1 years, respectively; P = 0.002) and were listed with a higher Model for End-Stage Liver Disease score (15.2 ± 7.5, 14.9 ± 7.6, and 18.1 ± 9.3, respectively; P = 0.001); they were also less frequently noted to have inflammatory bowel disease in comparison with European Americans (71.4% versus 60.5%, P < 0.01). In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (odds ratio with respect to European Americans = 1.325, 95% confidence interval = 1.221-1.438). HLA associations in European Americans, Hispanics, and African Americans with PSC versus alcoholic liver disease were detected for HLA-B8, HLA-DR13, and protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, showed associations only in European Americans and Hispanics. In conclusion, African Americans with PSC who are listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC.