A. Geerts

Early Arterial Revascularization After Hepatic Artery Thrombosis May Avoid Graft Loss and Improve Outcomes in Adult Liver Transplantation

BACKGROUND Hepatic artery thrombosis (HAT) represents a devastating complication after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients. Treatments of HAT include thrombectomy and thrombolysis (with or without redo of the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver retransplantation, and clinical observation. METHODS We retrospectively analyzed data from 739 adult LTs between January 1992 and September 2009. HAT was classified as early (E-HAT), when occurring within the first 30 days after LT, or late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected clinically was confirmed by Doppler ultrasound and angiography in all cases. Attempted revascularization was defined as early (ER) if performed within the first 2 weeks after LT and late (LR) if performed between 15 and 30 days. RESULTS After a median follow-up (FU) of 62 months (range, 1-227 months), HAT occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L-HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to 62% graft salvage; it was 81% when the revascularization was performed within the first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The overall incidence of BC among rescued grafts was 54% without graft loss during FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E-HAT and L-HAT, respectively (P = ns). CONCLUSIONS Urgent revascularization in cases of early HAT may decrease graft loss, especially when performed within the first week after LT, with improved overall outcomes.

INVASIVE ASPERGILLOSIS IN PATIENTS WITH CIRRHOSIS, A CASE REPORT AND REVIEW OF THE LAST 10 YEARS

Abstract Background: Untreated invasive aspergillosis (IA) is lethal, yet diagnosis is often delayed. Recognising the risk factors can lead to earlier diagnosis. We present a case of an invasive pulmonary aspergillosis in a patient with cirrhosis, who had been treated with corticosteroids for 2.5 weeks for alcoholic hepatitis. He was successfully treated with liposomal amphotericin B and caspofungin (first in combination, then caspofungin monotherapy). Purpose: to evaluate the role of aspergillosis in cirrhosis Methods: A literature search on aspergillosis in cirrhosis and liver failure patients was conducted in PubMed/ Medline (2002-dec 2012), according to pre-set selection criteria. Results: 20 out of 330 articles were retrieved, representing 43 patients with cirrhosis and/or liver failure who had an aspergillosis infection. Most Aspergillus (A.) infections were due to A. fumigatus and the lungs were the most frequent organ involved (42/43). 58% of the patients used steroids and mortality was 53,5%. The most frequent used antifungal was caspofungin. Discussion: Diagnosis of IA is difficult and there might be a delay in diagnosis since cirrhosis is not recognised as one of the classical risk factors. Mortality was 53,5%, but this is lower than in previous decades. Since voriconazole is hepatotoxic, treatment with caspofungin and /or amphotericin is preferable. Conclusion: Early recognition of aspergillosis in a cirrhosis/ liver failure patient is crucial and should prompt direct treatment.

Improved results for adult split liver transplantation with extended right lobe grafts: could we enhance its application?

OBJECTIVE Split liver transplantation (SLT) allows grafting of 2 recipients with 1 allograft. Results of adult SLT have improved since its first introduction. Children benefit most from SLT, while among some adult liver transplanters there are concerns about splitting a liver, turning a good quality graft into a marginal one. We performed a single center retrospective review to address this issue. PATIENTS AND METHODS Between June 2001 and August 2008, we performed 22 extended right liver graft (eRLG) transplantations in 21 adult patients. RESULTS Eleven donors (50%) did not meet the Eurotransplant criteria for optimal donors. Forty-one percent of eRLG donors showed hemodynamic instability at the time of harvest. Eighteen (82%) splitting procedures were performed ex situ. The main indications for transplantation were alcoholic liver cirrhosis (32%), hepatitis C-related cirrhosis (18%), and acute liver failure (18%). Mean recipient age was 54 years (range, 17-69 years); median Model for End-Stage Liver Disease (MELD) score was 15 (range, 7-40). Patients were followed for a median of 16 months (range, 4-92 months) following transplantation. We observed 5 (23%) vascular and 3 (14%) biliary complications. Overall patient survival was 84% at 3 years; overall graft survival was 79%. For the 11 patients who had undergone transplantation after 2007, we observed a 100% patient and graft survival. CONCLUSION After an initial learning curve and provided careful selection, exceptions to classical donor criteria for splitting can be accepted with successful outcomes comparable to those after whole liver transplantation.

Pathophysiology and management of post resection liver failure

Abstract Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0–30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and non-parenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

P739 RISK FACTORS AND TREATMENT OUTCOMES IN GENOTYPE 1 AND GENOTYPE 4 HEPATITIS C INFECTED PATIENTS FROM A REAL WORLD DATA ANALYSIS IN EUROPE

P738 NO CLINICALLY RELEVANT DRUG–DRUG INTERACTIONS BETWEEN FALDAPREVIR AND PEGYLATED INTERFERON a-2a PLUS RIBAVIRIN IN HCV-INFECTED PATIENTS: PHARMACOKINETIC ANALYSES FROM TWO PHASE II STUDIES M. Bourliere, M. Sulkowski, M.P. Manns, T. Asselah, P. Ferenci, S. Pol, T. Berg, J. Lalezari, A.-M. Quinson, Y. Datsenko, J. Scherer, C.-L. Yong, F. Huang. Hopital Saint Joseph, Marseille, France; Johns Hopkins University School of Medicine, Baltimore, MD, United States; Hannover Medical School, Hannover, Germany; Hopital Beaujon, APHP, University Paris-Diderot and INSERM CRB 3, Clichy, France; Medical University of Vienna, Vienna, Austria; Hopital Cochin, Paris, France; Universitatsklinikum Leipzig AoR, Leipzig, Germany; Quest Clinical Research and University of California-San Francisco, San Francisco, CA, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United States; Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany E-mail: mbourliere@hopital-saint-joseph.fr

873 ANGIOGENIC CHANGES IN A NEW MOUSE MODEL FOR HEPATOCELLULAR CARCINOMA ASSESSED WITH STATE-OF-THE-ART IMAGING TECHNOLOGY

Background: The increasing incidence of hepatocellular carcinoma in Western countries has led to an expanding interest in this field. A vast need of experimental models that mimic the natural pathogenesis of hepatocellular carcinoma in a short time period is present. The goal of our study was (1) to develop an efficient mouse model for hepatocellular carcinoma research, (2) to assess time-dependent angiogenic changes and (3) to investigate tumour growth and neo-vascularisation using state-of-the-art imaging techniques. Methods: 5-week-old male mice received weekly intraperitoneal injections with N-nitrosodiethylamine (DEN) (35 mg/kg bodyweight) and samples were taken at several time points. Histology, ELISA and immunohistochemical stainings were used to identify the HCC-lesions and to quantify angiogenic factors VEGF and PlGF. HCC livers (25W) were perfused with Batson’s n°17 solution to produce vascular casts (arterial and venous). A state-of-the-art multimodal microPET/CT was used for in vivo detection of HCC-lesions with [18F]-fluoromethylcholine ([18F]FMCH) and for 3D-reconstruction of the vascular casts. Results: After 16W of DEN-injections a mild fibrosis (F1-F2) and dysplastic lesions appear, resulting in a pre-malignant environment. An increase of angiogenic factors VEGF and PlGF takes place, but not explicit enough to induce an increase in endothelial cells, which were upregulated after 20W. After 25W of DEN-injections, the dysplastic lesions have progressed to vascularised exophytic tumours which are macroscopically visible and give rise to a further increase in angiogenic factors, leading to the formation of new blood vessels. HCC-lesions were characterised by an increased uptake of [18F]FMCH, allowing visualisation of these hotspots (>3mm) with microPET/CT (figure 1). The vascular casts of HCC-livers clearly revealed the chaotic pattern and hierarchically disorganisation of tumour induced blood vessels (figure 2). Arteries formed a circumferential mantle around the hepatic tumours, while the central tumour regions showed a lower arterial density (figure 3). Electron microscopy revealed several angiogenic spots, with mostly sprouting angiogenesis, yet intussusceptive angiogenesis was also seen (figure 3). Conclusion: While most DEN-induced models take at least one year to develop tumours, weekly injections with DEN give rise to tumour occurrence after 25W. The well vascularised orthotopic tumours are a representative model for HCC and can serve as an excellent platform for the development of new therapeutic targets. The CT-reconstructions of vascular casts can be used as an interesting tool to study angiogenesis in animal models, especially for testing angiogenesis-inhibiting therapies. Furthermore, [18F]FMCH PET imaging may be clinically relevant for the visualization of HCC-lesions.

782 N-GLYCOSYLATION PATTERNS OF SERUM PROTEINS TO MAKE THE DISTINCTION BETWEEN STEATOSIS OF THE LIVER AND NON-ALCOHOLIC STEATOHEPATITIS IN OBESE PATIENTS SCHEDULED FOR BARIATRIC SURGERY

781 NOR-UDCA ATTENUATES PROGRESSION OF NASH N. Beraza, L. Ofner-Ziegenfuss, H. Ehedego, M. Boekschoten, M. Mueller, M. Trauner, C. Trautwein. Internal Medicine, University Hospital Aachen, Aachen, Germany; Metabolomics 2, CICbioGUNE, Derio, Spain; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Departments of Medicine and Pathology, Medical University Graz, Graz, Austria; Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands E-mail: nberaza@cicbiogune.es