- Email: [email protected]
179 EARLY AND LATE INDICATIONS OF EVEROLIMUS AFTER LIVER TRANSPLANTATION
POSTERS maybe due to immunosuppressive therapy. Further studies are needed to explore best time-point of iVSIL-application in the oLTXsetting. 179 EARLY AND LATE INDICATIONS OF EVEROLIMUS AFTER LIVER TRANSPLANTATION I. Bilbao1 , C. Dopazo1 , J. Lazaro1 , G. Sapisochin1 , L. Castells2 , R. Rodriguez1 , A. Guevara1 , R. Charco1 . 1 Servicio de Cirugia Hepatobiliopancreatica y Trasplantes Digestivos, 2 Hepatologia y Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain E-mail: [email protected] Aim: Everolimus (Ever) is an mTor inhibitor with immunosuppressant indication on renal and cardiac transplantation. The objetive of this study is to analyze the uses and management on liver transplantation (LT). Material and Methods: Since October 1988 to July 2011, 972 liver transplantations were performed in our center. Seventy-four (7.6%) have received Everolimus. Demographic characteristics of these patients, indication and timing of conversion, the evolution and mean follow-up after conversion, the adverse events and withdrawal rate have been analyzed. Results: Mean age at time of conversion was 58±10 years (r: 27–74). The indications of conversion were: refractory rejection 22(29.7%); HCC out of Milan criteria in explanted liver 13(16.6%); HCC recurrence post-LT 6(8.1%); “de novo” Tumor 13(17.6%); post-LT renal insufficiency 7(9.5%); neurotoxicity 9 (12.2%) and others 4(5.4%). Mean time from LT to conversion was 26±42 months (r: 0.5–160), median 6m. Mean follow-up post-conversion was 15±14 (r: 0.5–56), median12 months. At time of conversion, 19 patients suffered renal insufficiency, 25 arterial hypertension, 21 diabetes mellitus and 29 hyperlipidemia. Preconversion immunosuppressant regimen was based on: 69 Tacrolimus, 4 Cyclosporin y 1 MMF. Postconversion regimen was Tacrolimus+Ever 53; Cyclosporine+Ever 4; Ever±MMF±steroids 10; Ever±steroids 7. Mean trough levels were arround 3 ng/ml. Out of the 74 patients, 51 (69%) resolved the cause of conversion. More than half of the patients with renal insufficiency and 7 out of 21 patients with diabetes mellitus ameliorated the basal status. The main adverse event was hyperlipidemia (42%). Thirteen patients withdrew the drug due to inefficiency (7) and resolution of adverse event (6). Conclusion: Everolimus at low doses (trough levels around 3 ng/ml), in combination with Tacrolimus or Cyclosporin is a safe and efficient immunosuppressant with multiples indications in early and late post-LT period. 180 RECIPIENT’S VITAMIN D RECEPTOR GENETIC POLYMORPHISMS IDENTIFY HCV POSITIVE LIVER TRANSPLANTED PATIENTS AT LOWER RISK OF GRAFT FIBROSIS PROGRESSION DUE TO RECURRENT HEPATITIS C D. Bitetto1 , E. Falleti1 , S. Cmet1 , A. Cussigh1 , E. Fornasiere1 , C. Avellini2 , C. Fabris1 , M. Pirisi3 , P. Toniutto1 . 1 Dept. of Medical Sciences Clinical and Experimental, 2 Pathology, University of Udine, Udine, 3 Internal Medicine, University of Novara, Novara, Italy E-mail: [email protected] Background and Aim: Vitamin D receptor (VDR) genetic polymorphisms may confer susceptibility to immune-mediated liver diseases and vitamin D serum levels have been associated with poor antiviral response and worse fibrosis progression in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether recipient’s VDR genetic polymorphisms might influence liver fibrosis progression due to recurrent HCV. Methods: From 1996 to 2010 one hundred and one consecutive HCV positive liver transplanted recipients (72 males) from our Centre, with at least 6 months of follow-up, were included in the study. S78
In each patient graft fibrosis, was assessed by means of annual per protocol or on demand liver biopsies and scored by Ishak. Genotypes for VDR polymorphic sites (FokI C>T, BsmI G>A, ApaI T>G, TaqI T>C) were assessed by RFLP. Results: After a median follow-up of 81 months (range 6–198), 61 (60.4%) and 39 (38.6%) recipients reached an Ishak staging score ≥2 and ≥3 respectively; 20 (19.8%) developed cirrhosis (Ishak staging ≥5). Recipients carrying BsmI A/A and TaqI C/C genotypes reached a staging score ≥2 and ≥3 less frequently compared to those carrying the other genotypes (5/16 Vs 56/85, p = 0.013 for BsmI; 5/15 Vs 56/86, p = 0.025 for TaqI) for staging score ≥2 and (2/16 Vs 37/85, p = 0.024 for BsmI; 2/15 Vs 37/86, p = 0.042 for TaqI) for staging score ≥3. None of the recipient carrying these BsmI and TaqI genotypes developed cirrhosis (0/16 Vs 20/85, p = 0.036 for BsmI; 0/15 Vs 20/86 p = 0.037 for TaqI). No association was found between ApaI or FokI and fibrosis progression. By stepwise logistic regression analysis (donor and recipient age and gender, occurrence of rejection, biliary strictures, MELD score, cold ischemia time, type of immune-suppression, diabetes and VDR polymorphisms as covariates) the carriage of BsmI A/A genotype was confirmed as independent predictor of not reaching both Ishak staging score ≥2 (OR 0.212, p = 0.014) and ≥3 (OR 0.154, p = 0.027) while recurrent cirrhosis was independently predicted only by recipient gender. Conclusions: The evaluation of recipient VDR genetic polymorphisms may represent a useful tool to identify patients at lower risk to develop more severe graft fibrosis progression due to recurrent HCV. 181 TREATMENT WITH PEGYLATED INTERFERON AND RIBAVIRIN DURING EARLY ACUTE PHASE OF THE HEPATITIS C RECURRENCE VS LATE HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION I. Campos-Varela1,2 , J.I. Esteban1,2 , I. Bilbao2,3 , F. Rodr´ıguez-Fr´ıas2,4 , H. Allende5 , R. Charco3 , R. Esteban1,2 , L. Castells1,2 . 1 Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Aut` onoma de Barcelona, Barcelona, 2 Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 3 Liver Transplant Unit, Department of HPB-Surgery and Transplant, 4 Biochemistry Laboratory, 5 Pathology Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Aut` onoma de Barcelona, Barcelona, Spain E-mail: [email protected] Background: Optimal interval to start antiviral treatment for hepatitis-C-virus (HCV) after liver transplantation (LT) is not known. Aim: Retrospective comparison of the efficacy of early (acutelobulillar-hepatitis) vs late (chronic-active-hepatitis) treatment of the HCV-recurrence with peg-interferon and ribavirin in 107 LTrecipients. Patients and Methods: HCV-LT patients treated for HCV-recurrence between 2001–2010 were included. Patients with non-1 genotype, HIV-coinfection, or colestatic recurrence were excluded. Patients were grouped according to the timing of treatment into early (ET) and differed treatment (DT) groups. Results: Of 152 treated patients during the study period, 107 were included, of whom 53 (57%) completed treatment. Overall, 64 (60%) were assigned to group of ET, and 43 (40%) to group of DT. Median interval from LT to antiviral treatment was 3 (range 1–19) and 18 months (range 7–240), p < 0.0001, respectively. Both patients groups were similar regard to baseline characteristics, except for higher viral load 6.7 log IU/mL (range 4.9–8.2) vs 6.5 log IU/mL (range 3.8–7.5), p = 0.05, AST 242 IU/mL (range 27–297) vs 179 IU/mL (range 21–878), p = 0.03 and bilirrubin 2 mg/dL (range 0.3–26) and 1 mg/dL (range 0.3–31), p < 0.0001 and lower haemoglobin level 12.1 g/dL (range 9.2–15) and 13 g/dL (range 10–16), p = 0.01. There
Journal of Hepatology 2012 vol. 56 | S71–S224
In each patient graft fibrosis, was assessed by means of annual per protocol or on demand liver biopsies and scored by Ishak. Genotypes for VDR polymorphic sites (FokI C>T, BsmI G>A, ApaI T>G, TaqI T>C) were assessed by RFLP. Results: After a median follow-up of 81 months (range 6–198), 61 (60.4%) and 39 (38.6%) recipients reached an Ishak staging score ≥2 and ≥3 respectively; 20 (19.8%) developed cirrhosis (Ishak staging ≥5). Recipients carrying BsmI A/A and TaqI C/C genotypes reached a staging score ≥2 and ≥3 less frequently compared to those carrying the other genotypes (5/16 Vs 56/85, p = 0.013 for BsmI; 5/15 Vs 56/86, p = 0.025 for TaqI) for staging score ≥2 and (2/16 Vs 37/85, p = 0.024 for BsmI; 2/15 Vs 37/86, p = 0.042 for TaqI) for staging score ≥3. None of the recipient carrying these BsmI and TaqI genotypes developed cirrhosis (0/16 Vs 20/85, p = 0.036 for BsmI; 0/15 Vs 20/86 p = 0.037 for TaqI). No association was found between ApaI or FokI and fibrosis progression. By stepwise logistic regression analysis (donor and recipient age and gender, occurrence of rejection, biliary strictures, MELD score, cold ischemia time, type of immune-suppression, diabetes and VDR polymorphisms as covariates) the carriage of BsmI A/A genotype was confirmed as independent predictor of not reaching both Ishak staging score ≥2 (OR 0.212, p = 0.014) and ≥3 (OR 0.154, p = 0.027) while recurrent cirrhosis was independently predicted only by recipient gender. Conclusions: The evaluation of recipient VDR genetic polymorphisms may represent a useful tool to identify patients at lower risk to develop more severe graft fibrosis progression due to recurrent HCV. 181 TREATMENT WITH PEGYLATED INTERFERON AND RIBAVIRIN DURING EARLY ACUTE PHASE OF THE HEPATITIS C RECURRENCE VS LATE HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION I. Campos-Varela1,2 , J.I. Esteban1,2 , I. Bilbao2,3 , F. Rodr´ıguez-Fr´ıas2,4 , H. Allende5 , R. Charco3 , R. Esteban1,2 , L. Castells1,2 . 1 Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Aut` onoma de Barcelona, Barcelona, 2 Centro de Investigaci´ on Biom´edica en Red de Enfermedades Hep´ aticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, 3 Liver Transplant Unit, Department of HPB-Surgery and Transplant, 4 Biochemistry Laboratory, 5 Pathology Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Aut` onoma de Barcelona, Barcelona, Spain E-mail: [email protected] Background: Optimal interval to start antiviral treatment for hepatitis-C-virus (HCV) after liver transplantation (LT) is not known. Aim: Retrospective comparison of the efficacy of early (acutelobulillar-hepatitis) vs late (chronic-active-hepatitis) treatment of the HCV-recurrence with peg-interferon and ribavirin in 107 LTrecipients. Patients and Methods: HCV-LT patients treated for HCV-recurrence between 2001–2010 were included. Patients with non-1 genotype, HIV-coinfection, or colestatic recurrence were excluded. Patients were grouped according to the timing of treatment into early (ET) and differed treatment (DT) groups. Results: Of 152 treated patients during the study period, 107 were included, of whom 53 (57%) completed treatment. Overall, 64 (60%) were assigned to group of ET, and 43 (40%) to group of DT. Median interval from LT to antiviral treatment was 3 (range 1–19) and 18 months (range 7–240), p < 0.0001, respectively. Both patients groups were similar regard to baseline characteristics, except for higher viral load 6.7 log IU/mL (range 4.9–8.2) vs 6.5 log IU/mL (range 3.8–7.5), p = 0.05, AST 242 IU/mL (range 27–297) vs 179 IU/mL (range 21–878), p = 0.03 and bilirrubin 2 mg/dL (range 0.3–26) and 1 mg/dL (range 0.3–31), p < 0.0001 and lower haemoglobin level 12.1 g/dL (range 9.2–15) and 13 g/dL (range 10–16), p = 0.01. There
Journal of Hepatology 2012 vol. 56 | S71–S224