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154 Immunogenicity and safety of a novel adjuvanted hepatitis B candidate vaccine in liver transplant patients
52
Poster Sessions
had rapid weight gain after interruption of treatment; 13/19 pts had a sustained response: evolution of BMI in this group: t0 33.5 + 4.4, t12m 29.8 + 3.8 (p<0.01) and waist circumference(cm): t0 111.7 + 11.1, t12m 96.3 + 9.5 (p<0.01). Conclusion: Orlistat is safe after LT. Minor dosis adjustments of immunosuppression are required. In 68% a sustained weight loss was observed with a follow up of 6 months.
153 THE PREDICTIVE VALUE OF NON-INVASIVE DIAGNOSTIC TOOLS TO DETECT HCC OR PRE-MALIGNANT DYSPLASTIC NODULES IN PATIENTS WITH ADVANCED CIRRHOSIS AND A HEPATIC MASS
M. Sorour 1 , F. Nevens 1 , C. Verslype 1 , L. Libbrecht 2 , D. Vanbeckevoort 3 , D. Billen 3 , R. Aerts 4 , J. Fevery 1 , T. Roskams 2 , J. Pirenne 4 . 1 Hepatology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 2 Histopathology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 3 Radiology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 4 Abdominal Transplant Surgery, KU Leuven/UZ Gasthuisberg, Leuven, Belgium Background: Patients with suspicion of HCC (without histological proof) are given priority on the liver transplant (LT) waiting list. To avoid erroneous allocation of the scarce liver grafts, it is crucial that the positive predictive value (PPV) of the non-invasive diagnostic techniques be high. Dysplastic nodules (Dyspl) are considered as pre-malignant. Methods: In a prospective cohort study, the value of NMR and α fetoprotein (AFP) to detect HCC and/or Dyspl was explored in all consecutive LT for cirrhosis between 1999 and 2003 (n=200). On histology 51 had HCC and 23 isolated Dyspl. Results: HCC was suspected on NMR in 59 pts; this was confirmed in 45 pts and 4 pts had only Dyspl (PPV for HCC or Dyspl: 76%). Elevated AFP (> 20 µg/ml) was found in 37 pts: 24 had HCC and 7 Dyspl (PPV: 84%); in postalcoholic/cryptogenic cirrhosis (n=85) with AFP↑ (=9), 8 had HCC and 1 Dyspl; in viral C and B cirrhosis (n=77) 12 had isolated Dyspl: 6 had AFF↑. Pts with suspicion of HCC on NMR and AFP↑ (n=25): 23 had HCC and 1 Dyspl (PPV: 92%). Conclusion: Elevated AFP is highly predictive for HCC in case of postalcoholic/cryptogenic cirrhosis and a hepatic mass. ‘So called’ false positive elevated AFP can partially be explained by the presence of dysplastic nodules. Only the combination of NMR and AFP↑ has an excellent PPV for the presence of HCC or dysplastic nodules.
154 IMMUNOGENICITY AND SAFETY OF A NOVEL ADJUVANTED HEPATITIS B CANDIDATE VACCINE IN LIVER TRANSPLANT PATIENTS
F. Nevens 1 , J.N. Zuckerman 2 , A. Burroughs 2 , M.C. Jung 3 , J.M. Bayas 4 , B. Kallinowski 5 , M. de la Mata 6 , C. Duvoux 7 , P. Neuhaus 8 , F. Saliba 9 , M. Buti 10 , J.P. Zarski 11 , F. Pons 12 , C. Vanlemmens 13 , V. Hamtiaux 14 , M. Stoffel 14 . 1 Department of Medicine, Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium; 2 Academic Unit of Travel Medicine and Vaccines, The Royal Free and University College School of Medicine, London, UK; 3 Medizinische Klinik II, Klinikum Grosshadern, Muenchen, Germany; 4 Servicio De Medicina Preventiva, Hospital Clinic, Barcelona, Spain; 5 I. Medizin Klinik, Universitaetsklinik Heidelberg, Heidelberg, Germany; 6 Unidad De Transplantes, Hospital Reina Sofia, Cordoba, Spain; 7 Hepato Gastro Enterologie, Hopital Henri Modor, Creteil, France; 8 Landesinstitut Fuer Tropenmedizin, Berlin, Germany; 9 Departement Des Maladies Du Foie, Hopital P. Brousse, Villejuif, France; 10 Servicio De Medicina Interna-Hepatologia, Hospital Vall D’Hebron, Barcelona, Spain Patients with advanced chronic liver disease are at increased risk of hepatitis B (HB) infection prior to and when undergoing liver transplantation and they have a suboptimal immune response to HB vaccines. We compared the immunogenicity of a new adjuvanted HB vaccine to a licensed HB vac-
cine in liver transplant candidates. Ninety-three pre-liver transplant patients were enrolled into the study to receive either adjuvanted HBsAg/AS04 vaccine on a 0, 21-day schedule or a double dose (2 x 20 µg HBsAg) of Engerix -B (GlaxoSmithKline Biologicals, Rixensart, Belgium) on a 0, 7, 21-day schedule. A booster dose of HBsAg/AS04 or double booster dose of Engerix -B was given 6-12 months after vaccination initiation. The percentage of subjects with seroprotective anti-HBs titers (≥ 10 mIU/ml) one month after booster was twice as high (p=0.035) in the HBsAg/AS04 group (60% or 18/30), compared to the Engerix -B group (32% or 8/25). The anti-HBs GMT also tended to be higher: 481 mIU/ml in the HBsAg/AS04 group, versus 279 mIU/ml in the Engerix -B group (p=0.641). 80% of subjects (16/20) who did not undergo liver transplantation before booster were seroprotected after HBsAg/AS04 booster, versus 60% (6/10) after Engerix -B. The HBsAg/AS04 vaccine had an acceptable safety profile despite slightly higher reactogenicity. An improved antibody response was observed in liver transplant candidates with 3 doses of HBsAg/AS04 vaccine, as compared to 4 double doses of Engerix -B. Pre-liver transplant candidates could benefit from the use of an adjuvanted HB vaccine to increase their protection against HB infection.
155 PREDICTORS OF OUTCOME OF LIVER TRANSPLANTATION IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA
G. Nicolini 1 , M. Merli 1 , F. Gentili 1 , G. Indrio 1 , M. Iappelli 2 , M. Rossi 2 , P. Berloco 2 , U. Di Tondo 3 , A. Onetti Muda 3 , S. Ginanni Corradini 1 , N. Walter 2 , A.F. Attili 1 . 1 Dipartimento Di Medicina Clinica - II Gastroenterologia - Università Di Roma La Sapienza, Rome, Italy; 2 Dipartimento Di Chirurgia Generale - Università Di Roma La Sapienza, Rome, Italy; 3 Anatomia Patologica - Università Di Roma La Sapienza, Rome, Italy Available studies to define the optimal upper limits of tumor size and number as predictors for outcome after orthotopic liver transplantation (OLT) have given conflicted results. We retrospectively analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 10-year period. Predictors and survival according to the Milan1 and UCSF2 criteria were also examined. Our cohort included 60M and 12F, mean age 54±8yrs and mean follow-up 22±26months. Diagnosis of HCC was confirmed at histology after OLT and 60% of patients underwent loco-regional therapy before OLT. Origin of cirrhosis was post-viral in 71%, Child class was B or C in 90%, HCC was multifocal in 57%, 68% had vascular involvement and 70% positive nodes. Cumulative size of lesion was 0-3cm in 38%, 0-5 in 54% and >5cm in 33%. Sixty per cent of patients met the Milan criteria and 67% met the UCSF criteria. Twenty-three patients died and 52% for tumor’s recurrence. At multivariate analysis, tumor size >8cm in maximum diameter was predictive of death due tumor’s recurrence. The 1-and 2-year survival were 87% and 64% for patients who met the Milan criteria vs 41% and 35% for patients exceeding these limits (p=0.01). Among patients who met the UCSF criteria, the 1-and 2-year survival were 86% and 67% compared with 31% and 23% for patients exceeding the criteria (p=0.0008). The Milan criteria for selection of cirrhotic patients with HCC might be too restrictive and UCSF criteria may be adopted. 1) N Engl J Med 1996. 2) Hepatology 2001.
156 DOSE OF TACROLIMUS REQUIRED TO MAINTAIN THERAPEUTIC LEVELS DECERASES POST LIVER TRANSPLANT IN HEPATITIS C (HCV) RECIPIENTS
Y.H. Oo 1 , T. Dudley 1 , P.G. Nightingale 2 , G.H. Haydon 1 , D.J. Mutimer 1 . 1 Liver & Hepatobiliary Unit, The Queen Elizabeth Hospital, Birmingham, UK; 2 Statistical Department, Wolfson Building, The Queen Elizabeth Hospital, Birmingham, UK Introduction: Following orthotopic liver transplantation (OLT) graft reinfection by HCV is universal. We have noticed that a progressively lower
Poster Sessions
had rapid weight gain after interruption of treatment; 13/19 pts had a sustained response: evolution of BMI in this group: t0 33.5 + 4.4, t12m 29.8 + 3.8 (p<0.01) and waist circumference(cm): t0 111.7 + 11.1, t12m 96.3 + 9.5 (p<0.01). Conclusion: Orlistat is safe after LT. Minor dosis adjustments of immunosuppression are required. In 68% a sustained weight loss was observed with a follow up of 6 months.
153 THE PREDICTIVE VALUE OF NON-INVASIVE DIAGNOSTIC TOOLS TO DETECT HCC OR PRE-MALIGNANT DYSPLASTIC NODULES IN PATIENTS WITH ADVANCED CIRRHOSIS AND A HEPATIC MASS
M. Sorour 1 , F. Nevens 1 , C. Verslype 1 , L. Libbrecht 2 , D. Vanbeckevoort 3 , D. Billen 3 , R. Aerts 4 , J. Fevery 1 , T. Roskams 2 , J. Pirenne 4 . 1 Hepatology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 2 Histopathology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 3 Radiology, KU Leuven/UZ Gasthuisberg, Leuven, Belgium; 4 Abdominal Transplant Surgery, KU Leuven/UZ Gasthuisberg, Leuven, Belgium Background: Patients with suspicion of HCC (without histological proof) are given priority on the liver transplant (LT) waiting list. To avoid erroneous allocation of the scarce liver grafts, it is crucial that the positive predictive value (PPV) of the non-invasive diagnostic techniques be high. Dysplastic nodules (Dyspl) are considered as pre-malignant. Methods: In a prospective cohort study, the value of NMR and α fetoprotein (AFP) to detect HCC and/or Dyspl was explored in all consecutive LT for cirrhosis between 1999 and 2003 (n=200). On histology 51 had HCC and 23 isolated Dyspl. Results: HCC was suspected on NMR in 59 pts; this was confirmed in 45 pts and 4 pts had only Dyspl (PPV for HCC or Dyspl: 76%). Elevated AFP (> 20 µg/ml) was found in 37 pts: 24 had HCC and 7 Dyspl (PPV: 84%); in postalcoholic/cryptogenic cirrhosis (n=85) with AFP↑ (=9), 8 had HCC and 1 Dyspl; in viral C and B cirrhosis (n=77) 12 had isolated Dyspl: 6 had AFF↑. Pts with suspicion of HCC on NMR and AFP↑ (n=25): 23 had HCC and 1 Dyspl (PPV: 92%). Conclusion: Elevated AFP is highly predictive for HCC in case of postalcoholic/cryptogenic cirrhosis and a hepatic mass. ‘So called’ false positive elevated AFP can partially be explained by the presence of dysplastic nodules. Only the combination of NMR and AFP↑ has an excellent PPV for the presence of HCC or dysplastic nodules.
154 IMMUNOGENICITY AND SAFETY OF A NOVEL ADJUVANTED HEPATITIS B CANDIDATE VACCINE IN LIVER TRANSPLANT PATIENTS
F. Nevens 1 , J.N. Zuckerman 2 , A. Burroughs 2 , M.C. Jung 3 , J.M. Bayas 4 , B. Kallinowski 5 , M. de la Mata 6 , C. Duvoux 7 , P. Neuhaus 8 , F. Saliba 9 , M. Buti 10 , J.P. Zarski 11 , F. Pons 12 , C. Vanlemmens 13 , V. Hamtiaux 14 , M. Stoffel 14 . 1 Department of Medicine, Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium; 2 Academic Unit of Travel Medicine and Vaccines, The Royal Free and University College School of Medicine, London, UK; 3 Medizinische Klinik II, Klinikum Grosshadern, Muenchen, Germany; 4 Servicio De Medicina Preventiva, Hospital Clinic, Barcelona, Spain; 5 I. Medizin Klinik, Universitaetsklinik Heidelberg, Heidelberg, Germany; 6 Unidad De Transplantes, Hospital Reina Sofia, Cordoba, Spain; 7 Hepato Gastro Enterologie, Hopital Henri Modor, Creteil, France; 8 Landesinstitut Fuer Tropenmedizin, Berlin, Germany; 9 Departement Des Maladies Du Foie, Hopital P. Brousse, Villejuif, France; 10 Servicio De Medicina Interna-Hepatologia, Hospital Vall D’Hebron, Barcelona, Spain Patients with advanced chronic liver disease are at increased risk of hepatitis B (HB) infection prior to and when undergoing liver transplantation and they have a suboptimal immune response to HB vaccines. We compared the immunogenicity of a new adjuvanted HB vaccine to a licensed HB vac-
cine in liver transplant candidates. Ninety-three pre-liver transplant patients were enrolled into the study to receive either adjuvanted HBsAg/AS04 vaccine on a 0, 21-day schedule or a double dose (2 x 20 µg HBsAg) of Engerix -B (GlaxoSmithKline Biologicals, Rixensart, Belgium) on a 0, 7, 21-day schedule. A booster dose of HBsAg/AS04 or double booster dose of Engerix -B was given 6-12 months after vaccination initiation. The percentage of subjects with seroprotective anti-HBs titers (≥ 10 mIU/ml) one month after booster was twice as high (p=0.035) in the HBsAg/AS04 group (60% or 18/30), compared to the Engerix -B group (32% or 8/25). The anti-HBs GMT also tended to be higher: 481 mIU/ml in the HBsAg/AS04 group, versus 279 mIU/ml in the Engerix -B group (p=0.641). 80% of subjects (16/20) who did not undergo liver transplantation before booster were seroprotected after HBsAg/AS04 booster, versus 60% (6/10) after Engerix -B. The HBsAg/AS04 vaccine had an acceptable safety profile despite slightly higher reactogenicity. An improved antibody response was observed in liver transplant candidates with 3 doses of HBsAg/AS04 vaccine, as compared to 4 double doses of Engerix -B. Pre-liver transplant candidates could benefit from the use of an adjuvanted HB vaccine to increase their protection against HB infection.
155 PREDICTORS OF OUTCOME OF LIVER TRANSPLANTATION IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA
G. Nicolini 1 , M. Merli 1 , F. Gentili 1 , G. Indrio 1 , M. Iappelli 2 , M. Rossi 2 , P. Berloco 2 , U. Di Tondo 3 , A. Onetti Muda 3 , S. Ginanni Corradini 1 , N. Walter 2 , A.F. Attili 1 . 1 Dipartimento Di Medicina Clinica - II Gastroenterologia - Università Di Roma La Sapienza, Rome, Italy; 2 Dipartimento Di Chirurgia Generale - Università Di Roma La Sapienza, Rome, Italy; 3 Anatomia Patologica - Università Di Roma La Sapienza, Rome, Italy Available studies to define the optimal upper limits of tumor size and number as predictors for outcome after orthotopic liver transplantation (OLT) have given conflicted results. We retrospectively analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 10-year period. Predictors and survival according to the Milan1 and UCSF2 criteria were also examined. Our cohort included 60M and 12F, mean age 54±8yrs and mean follow-up 22±26months. Diagnosis of HCC was confirmed at histology after OLT and 60% of patients underwent loco-regional therapy before OLT. Origin of cirrhosis was post-viral in 71%, Child class was B or C in 90%, HCC was multifocal in 57%, 68% had vascular involvement and 70% positive nodes. Cumulative size of lesion was 0-3cm in 38%, 0-5 in 54% and >5cm in 33%. Sixty per cent of patients met the Milan criteria and 67% met the UCSF criteria. Twenty-three patients died and 52% for tumor’s recurrence. At multivariate analysis, tumor size >8cm in maximum diameter was predictive of death due tumor’s recurrence. The 1-and 2-year survival were 87% and 64% for patients who met the Milan criteria vs 41% and 35% for patients exceeding these limits (p=0.01). Among patients who met the UCSF criteria, the 1-and 2-year survival were 86% and 67% compared with 31% and 23% for patients exceeding the criteria (p=0.0008). The Milan criteria for selection of cirrhotic patients with HCC might be too restrictive and UCSF criteria may be adopted. 1) N Engl J Med 1996. 2) Hepatology 2001.
156 DOSE OF TACROLIMUS REQUIRED TO MAINTAIN THERAPEUTIC LEVELS DECERASES POST LIVER TRANSPLANT IN HEPATITIS C (HCV) RECIPIENTS
Y.H. Oo 1 , T. Dudley 1 , P.G. Nightingale 2 , G.H. Haydon 1 , D.J. Mutimer 1 . 1 Liver & Hepatobiliary Unit, The Queen Elizabeth Hospital, Birmingham, UK; 2 Statistical Department, Wolfson Building, The Queen Elizabeth Hospital, Birmingham, UK Introduction: Following orthotopic liver transplantation (OLT) graft reinfection by HCV is universal. We have noticed that a progressively lower