MINUS HBIG WITHDRAWAL IN POST-ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS FOR CHRONIC HEPATITIS B

POSTERS 574 INTERIM 48 WEEK RESULTS OF A RANDOMIZED TRIAL OF EMTRICITABINE/TENOFOVIR DF PLUS/MINUS HBIG WITHDRAWAL IN POST-ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS FOR CHRONIC HEPATITIS B L. Teperman1 , J. Spivey2 , F. Poordad3 , T. Schiano4 , N. Bzowej5 , P. Martin6 , D. Coombs7 , K.R. Hirsch7 , J. Anderson7 . 1 New York University Medical Center, New York, NY, 2 Emory Healthcare, Atlanta, GA, 3 Cedars-Sinai Medical Center, Los Angeles, CA, 4 Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY, 5 California Pacific Medical Center, San Francisco, CA, 6 Schiff Liver Institute, University of Miami Miller School of Medicine, Miami, FL, 7 Gilead Sciences, Inc., Durham, NC, USA E-mail: [email protected] Objective: To evaluate the safety and efficacy of emtricitabine/ tenofovir DF (FTC/TDF) in preventing chronic hepatitis B (CHB) recurrence post-OLT withdrawal of HBIG. Methods: Stable patients ≥12 weeks post-OLT with a creatinine clearance ≥40 mL/min, no CHB recurrence post-OLT, and <1 year TDF treatment prior to OLT were eligible. Patients were treated for 24 weeks with FTC/TDF plus HBIG and at week (W) 24 randomized (1:1) to continue HBIG and FTC/TDF or discontinue HBIG continuing FTC/TDF. Primary analysis conducted after 48 weeks of randomized treatment (W72); all available data reported through W96. Results: 40 patients were enrolled, 3 discontinued before W24 and 37 were randomized (18 FTC/TDF & 19 FTC/TDF+HBIG). 35 patients (88%) completed W72 and 28 have thus far completed the study (W96). Baseline characteristics: median age 59 years, 80% male, 37.5% Asian/32.5% Caucasian/25% Black. 40% had hepatocellular carcinoma and 47% had detectable HBV DNA at time of transplant. Median time (range) since OLT was 3.4 years (0.3, 17.7). 33 patients entered the study with mild (≥50 to 80 ml/min; N = 24) to moderate (<50 ml/min; N = 9) renal impairment. One patient (FTC/TDF group) experienced a transient unconfirmed increase in HBV DNA to 314 copies/mL (W84 visit only), coincident with documented medication non-compliance, and returned to undetectable HBV DNA upon repeat testing and was HBV DNA and HBsAg negative at their final study visit (W96). Overall, renal function remained stable over time; W72 median change from baseline in creatinine for the three renal groups was 0 (−0.2, 0.1), 0 (−0.3, 0.6), and −0.20 (−0.4, 0), respectively. Six patients with mild renal impairment at baseline had confirmed creatinine clearance <50 mL/min (one also had a confirmed ≥0.5 mg/dL increase in creatinine); 3 patients remain on treatment and 2 completed the study. One patient died (considered unrelated) and two discontinued study due to adverse events. Conclusion: FTC/TDF was well tolerated in post-OLT patients with normal to moderately impaired renal function with appropriate monitoring and dose adjustment. This interim analysis suggests that FTC/TDF is effective in preventing CHB recurrence after discontinuing HBIG. 575 A REVIEW OF LATE ACUTE REJECTION IN THE ERA OF TACROLIMUS THERAPY; A STUDY OF ITS NATURAL HISTORY, INCIDENCE, RISK FACTORS AND GRAFT SURVIVAL P.H. Thurairajah, M. Carbone, H. Bridgestock, P. Thomas, S. Hebbar, B. Gunson, T. Shah, J. Neuberger. Liver Unit, Queen Elizabeth Hospital, Birmingham, UK E-mail: [email protected] Background: Late acute rejection (LAR) is a serious complication following liver transplantation characterised histologically by mononuclear portal hepatitis, endothelialitis and bile duct injury. It is associated with poor clinical outcomes. We reviewed our experience of managing LAR over a decade and describe its natural S234

history, risk factors and poor prognostic indicators of graft survival in the era of Tacrolimus therapy. Methods: Data on 970 consecutive adult liver transplants who survived for at least 3 months between 1st January 2000 to 31st August 2009 were reviewed. LAR was defined as histologically proven acute cellular rejection occurring after 90 days and cases were compared against non rejecting OLT recipients. Results: 103 patients had LAR during this period with a total of 134 patient episodes. The incidence of LAR was 11%, mean time to LAR was 565 days (median – 311 days, range 90–2922 days). Recurrent LAR was infrequent (17%). The highest rates for LAR were in seronegative hepatitis (17%), PBC (16%), and PSC (13%) with an odds ratio of 2.3, 2.1 and 1.8 respectively compared to drug induced liver injury. Logistic regression showed that younger recipients and PBC were independent predictors of LAR (p < 0.001). Mean Tacrolimus levels were at their lowest levels 1 week prior to rejection (5.5, SD 2.6). Diarrhoea (n = 5) and non compliance (n = 4) were reported in a minority. Patient and graft survival were both worse in LAR patients (p < 0.01) with the best prognosis amongst early acute rejection cases. Poor response to treatment correlated with the development of early chronic rejection (r = 0.3, p < 0.01). 29 patients (28%) developed chronic rejection from which half died (n = 15). Conclusions: Autoimmune liver diseases are associated with an increased risk of LAR and in particular PBC is an independent risk factor along with younger recipients. There is a strong temporal relationship between low immunosuppression levels and LAR. Patients who have a poor biochemical response to treatment are at risk of developing chronic rejection. Graph survival is poorer with LAR. The histological appearance of early chronic rejection is a poor prognostic marker and should be considered for re-grafting. 576 POST-TRANSPLANT ENCEPHALOPATHY A.B. Tryc1,2 , A. Goldbecker1,2 , K. Afshar1,2 , G. Hamidi Shahrezaei1,2 , 1,2 S. Rumke ¨ , H. Barg-Hock3 , C. Strassburg4 , K. Weissenborn1,2 . 1 Integrated Research and Treatment Center (IFB) Transplantation, 2 Neurology and Clinical Neurophysiology, 3 Visceral and Transplantation Surgery, 4 Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany E-mail: [email protected] Background and Aims: Neurological complications occur in up to 40% of patients after orthotopic liver transplantation (OLT). Most frequent is the so-called post-transplant encephalopathy which is characterized especially by disturbance of consciousness. Data about risk factors, pathophysiology and clinical course are sparse and contradictory. Representative prospective studies are missing. The aim of our ongoing prospective study is to evaluate the prevalence of post-transplant encephalopathy after OLT, to identify risk factors and to assess the relationship between this complication and outcome. Methods: So far 103 patients (mean age 49 years; range 19–69 years) have been included into the study, and were regularly visited after OLT by a neurologist during their hospital stay. Patients with and without post-transplant encephalopathy were compared with regard to the presence of preoperative hepatic encephalopathy (HE), age, MELD score and biochemical parameters of liver and kidney function. In addition, the influence of posttransplant encephalopathy, HE before OLT, age and MELD score upon mortality after OLT was analyzed. Results: 17 patients had focal neurological deficits due to one ore more reasons: pontine myelinolyses (n = 4), posterior leucencephalopathy (n = 3), intracranial bleeding (n = 4), cerebral mycosis (n = 2), hypoxic brain damage (n = 1) and others. 20 showed transient confusion, hallucinations, disturbance of consciousness or convulsion without focal deficits or pathological brain imaging. 60

Journal of Hepatology 2011 vol. 54 | S209–S361