I. Bortoluzzi

Liver transplantation for viral hepatitis in 2015

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997–2010

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post‐transplant cancers were diagnosed—including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10‐year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios ‐ SIR=4.7, 95% CI: 3.2–6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1–17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high‐risk recipients like those with ALD.

Use of Grafts From Anti-HBc–Positive Donors in Liver Transplantation: A 5-Year, Single-Center Experience

INTRODUCTION Liver transplantation (OLT) is the treatment of choice for advanced hepatic disease. The growing gap between waiting list patients and the number of donations has led to acceptance of less than optimal donors. The aim of this study was to evaluate the 5-year experience with anti hepatitis B core antigen (HBc)-positive liver donors. PATIENTS AND METHODS All recipients of anti-HBc-positive grafts from January 2005 to December 2010 were evaluated annually after OLT for liver disease etiology, Model for End-Stage Liver Disease (MELD) score, and the presence of hepatocellular carcinoma (HCC) liver biopsy histology and serology for hepatitis B virus (HBsAg, anti-HBs, HBV-DNA), hepatitis C virus, and hepatitis D virus as well as antiviral prophylaxis to prevent de novo HBV. RESULTS Among the 249 OLT performed from January 2005 to December 2010, (9.3%) cases used grafts from anti-HBc-positive donors. Etiologics of liver disease among the recipients were HBV (n = 13; 32.5%), HCV (n = 13; 32.5%) or other causes (n = 14; 35%). In 20 of the 40 patients (50%), HCC was found in the explanted organ. Of 40 recipients of anti-HBc-positive grafts 11 died, and 7 (17.5%) required retransplantation. Various regimens were employed as post-transplantation antiviral prophylaxis: (l) Immune globulin (25.8%); (2) Oral antiviral drugs (9.7%); and (3) combined prophylaxis (51.6%) or no treatment (12.9%). No difference was observed in patient or graft survival in relation to the etiology of liver disease, the MELD score, or the presence of HCC at the time of OLT, except graft survival was significantly reduced among recipient who underwent transplantation for non-HBV or non-HCV liver diseases compared with those engrafted due to viral hepatitis (P = .0062). No difference was observed in histologic features (grading and staging) compared with the antiviral prophylactic therapy; the 2 patients (5%) who developed de novo HBV had not received prophylaxis after OLT. CONCLUSIONS Matching anti-HBc-positive grafts to recipients without HBV infection before OLT, may be especially safe.

235 PREDICTORS OF RESPONSE TO ANTICOAGULANT THERAPY FOR THE TREATMENT OF PORTAL VEIN THROMBOSIS (PVT) IN CIRRHOSIS PATIENTS

234 FUNCTIONAL MAGNETIC RESONANCE IMAGING AND STROOP TEST TO STUDY FRONTAL CORTICAL FUNCTION IN PATIENTS WITH CIRRHOSIS AND MINIMAL HEPATIC ENCEPHALOPATHY E. Rodriguez, G. Pereira, G. Monica, O. Laura, L. Rami, C. Falcon, P. Gines. Hepatology, Hospital Clinic Barcelona, University of Barcelona, Centre Diagnostic per la Imatge, Hospital Cĺinic Barcelona, Institut Cĺinic de Neurociencies, Hospital Cĺinic Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain E-mail: ezrodrig@clinic.ub.es

New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation

The hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.

P930 BLEEDING-UNRELATED MORTALITY IS NOT INCREASED IN PATIENTS WITH CIRRHOSIS AND ASCITES ON TREATMENT WITH β-BLOCKERS: A META-ANALYSIS

volume per IBW (SV/IBW) correlated closely with CE in the HALT-C trial. We enlarge on this experience by assessing test deterioration (D) on prediction of CE. Data on N=223 HALT-C trial participants (Hepat;55:1019) in the Quantitative liver function test ancillary study were analyzed to assess the association between M24 QLSS tests and deterioration from baseline to the time to first CE (18 CE in 83 patients). Methods: CE = CTP score 7, variceal bleeding, ascites, encephalopathy, liver-death. Non-CE = transplantation, HCC, presumed HCC, and non-hepatic deaths. Patients were at risk from M24 (entry) to first CE or non-CE. Patients were evaluated every 3 months with maximal follow-up of 6 years (median 5.5 years). QLSS: PHM = (LSI + LBI)/2, SV/IBW (cc/kg), EPSA = {(4.342 − 2.008RR − 0.0209PHM + 18.15/R) + sqrt[313/(R + 0.5L) − logRR−9.6])/2, where RR (redistribution ratio) = [(Lp/Sp/2.5) + (Lp/BMp/17.5)]/2 and where, in planar counts, Lp, Sp, BMp, R = R lobe length, L = L lobe length} (Hep22:1113). Results: In univariate analyses, PHM, SV/IBW, and EPSA were significantly (p < 0.0001) associated with risk of CE by unadjusted analysis. Deterioration (D) from baseline was also significantly associated with CE for PHM (D-PHM) (p =0.0016) and EPSA (D-EPSA) (p = 0.051), but not SV/IBW (p=0.400). Multivariate Cox model analysis confined to PHM with D-PHM and EPSA with D-EPSA showed that both independently correlated significantly (PHM: p < 0.0001 and <0.0001, EPSA: p < 0.0001, 0.0079) with CE. Conclusions: 1. Hepatic dysfunction (PHM/EPSA) and SV/IBW predict subsequent CE. 2. Deterioration of hepatic function independently predicted CE.

P0074 : Prevalence and risk factors of metabolic syndrome after liver transplantation: a single centre experience

preservation procedure, the phenomenonwas significantly greater in MCD than in control livers, indicating a strong influence of fatty liver oxidative stress. Fluorescing fatty acids were not depleted, consistentlywithdynamicequilibria in liver lipidpool composition. Conclusions. The real time AF analysis allows tomonitor oxidative effects even in amodel ofmildmetabolic alterations, providing an AF support in experimental investigations on drug response and toxicity, and in the set-up of innovative organ preservation strategies.(Supported by Fondazione Cariplo, grant n◦2011-0439).

P931 EFFECTS OF NON-SELECTIVE β-BLOCKERS (NSBB) ON HEMODYNAMICS AND PARACENTESIS INDUCED CIRCULATORY DYSFUNCTION IN CIRRHOTIC PATIENTS UNDERGOING LARGE VOLUME PARACENTESIS (LVP)

volume per IBW (SV/IBW) correlated closely with CE in the HALT-C trial. We enlarge on this experience by assessing test deterioration (D) on prediction of CE. Data on N=223 HALT-C trial participants (Hepat;55:1019) in the Quantitative liver function test ancillary study were analyzed to assess the association between M24 QLSS tests and deterioration from baseline to the time to first CE (18 CE in 83 patients). Methods: CE = CTP score 7, variceal bleeding, ascites, encephalopathy, liver-death. Non-CE = transplantation, HCC, presumed HCC, and non-hepatic deaths. Patients were at risk from M24 (entry) to first CE or non-CE. Patients were evaluated every 3 months with maximal follow-up of 6 years (median 5.5 years). QLSS: PHM = (LSI + LBI)/2, SV/IBW (cc/kg), EPSA = {(4.342 − 2.008RR − 0.0209PHM + 18.15/R) + sqrt[313/(R + 0.5L) − logRR−9.6])/2, where RR (redistribution ratio) = [(Lp/Sp/2.5) + (Lp/BMp/17.5)]/2 and where, in planar counts, Lp, Sp, BMp, R = R lobe length, L = L lobe length} (Hep22:1113). Results: In univariate analyses, PHM, SV/IBW, and EPSA were significantly (p < 0.0001) associated with risk of CE by unadjusted analysis. Deterioration (D) from baseline was also significantly associated with CE for PHM (D-PHM) (p =0.0016) and EPSA (D-EPSA) (p = 0.051), but not SV/IBW (p=0.400). Multivariate Cox model analysis confined to PHM with D-PHM and EPSA with D-EPSA showed that both independently correlated significantly (PHM: p < 0.0001 and <0.0001, EPSA: p < 0.0001, 0.0079) with CE. Conclusions: 1. Hepatic dysfunction (PHM/EPSA) and SV/IBW predict subsequent CE. 2. Deterioration of hepatic function independently predicted CE.

141 USE OF ANTI-HBc POSITIVE DONORS IN LIVER TRANSPLANTATION: THE EXPERIENCE OF PADUA LIVER TRANSPLANT CENTRE

141 USE OF ANTI-HBc POSITIVE DONORS IN LIVER TRANSPLANTATION: THE EXPERIENCE OF PADUA LIVER TRANSPLANT CENTRE I. Bortoluzzi, M. Gambato, L. Albertoni, C. Mescoli, M. Pacenti, R. Cusinato, G. Germani, M. Senzolo, M. Rugge, G. Zanus, P. Boccagni, U. Cillo, P. Burra, F.P. Russo. Dept. of Surgical, Oncological and Gastroenterological Sciences, University Hospital Padova, Department of Medicine, Surgical Pathology & Cytopathology Unit, University Hospital Padova, Department of Molecular Medicine, Microbiology Unit, University Hospital Padova, Dept. of Surgical, Oncological and Gastroenterological Sciences, Hepatobiliary and Liver Transplantation Unit, University Hospital Padova, Padova, Italy E-mail: ilabortoluzzi@yahoo.it