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127 Liver transplantation for HCV-alcohol aetiology: Is the outcome similar to those to HCV or alcohol alone?
POSTERS
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CORTICOSTEROIDS (DEXAMETHASONE, DEX) INHIBIT INTERFERON A L P H A (IFN) P R O D U C T I O N A N D SIGNALING VIA THE JAK-STAT PATHWAY
S. Khatkar, E.L. Renner. Section of Hepatology, Department of Medicine,
University of Manitoba, Winnipeg, MB, Canada Background and Aim: IFN signaling via the J a ~ S t a t pathway plays a pivotal role in eliciting an antiviral state in HCV infected hepatocytes (Blindenbacher A, Gastroenterology 2003). Chronic hepatitis C virus (HCV) related end-stage liver disease is the single most common indication for liver transplantation (OLT) worldwide. After OLT, HCV re-infection of the graft is universal, associated with a 10 100-fold increase in HCV viremia, responds poorly to IFN-based therapy and follows an aggressive course leading to graft cirrhosis in ~25% of patients within a few years. Use of (high dose bolus) corticosteroids has been repeatedly found to be associated with accelerated progression (Beringuer M, J Hepatol 2005). We hypothesized that corticosteroids interfere with IFN production and/or signaling. Methods: 1Mio peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers (Ficoll-Hypaque gradient centrifugation) were cultured (48h) in the presence/absence of l u M DEX and stimulated (last 24h) with 100ug/ml of the viral mimetic poly(inosinic acid) poly(cytidylic acid) (PolyIC); IFN content of supernatant was analyzed by ELISA. C57BL/6 mice were treated for 5 days with 10mg/kg i.p. DEX/vehicle daily and injected (tail vein) with 1000 U/gb.w. IFN/vehicle 20 min prior to harvesting the livers. Liver nuclear extracts were analyzed for Stat binding by electromobility shift assay (EMSA) using a consensus sequence IFN sensitive response element. The specificity of the signal was confirmed by supershift using a monoclonal Stat 1 antibody. Results: In the absence of DEX, IFN production by PBMCs of 4 volunteers was stimulated by PolyIC from median 17 (range 9 20) to 30 (26 37) pg/ml (p <0.01); in the presence of DEX, it remained below detection limit with and without PolyIC stimulation (both p vs. absence of DEX <0.01). DEX pretreatment virtually abolished the IFN-induced EMSA signal in nuclear extracts of mouse liver (n 4 per group). Conclusion: The corticosteroid DEX inhibits (a) IFN production by PBMCs of healthy volunteers and (b) IFN-induced Jak Stat signaling in mouse liver. While the underlying mechanisms remain to be elucidated, this is consistent with corticosteroids blunting the IFN-induced antiviral state and may pertain to the increased HCV viremia/accelerated course and the poor response to IFN-based therapy of recurrent hepatitis C after OLT.
I•
ENDOTHELIN ANTAGONIST TREATMENT IN LIVER TRANSPLANTATION: D O N O R OR GRAFT?
X.-Y. Zhang, A.M. Wheatley. 1Department of Physiology, University of
Otago, Dunedin, New Zealand Background and Objective: Here we tested the hypothesis that donor pre-treatment with endothelin receptor antagonists in vivo is as effective as graft pre-treatment in vitro in the protection of the transplanted graft from hypothermic ischaemi~reperfusion (I R) injury. Methods: OLT with graft rearterialisation was performed in male Lewis under ether anaesthesia. The graft was stored in U W solution at 4~ for 17 hr prior to implantation. Donors were injected with an endothelin A receptor (ETAR) (ABT-627, 5 mg/kg), an ETBR antagonist (A192621.1, 6 mg/kg), both ETAR/ETBR antagonists or saline, 30 min prior to graft retrieval. In separate groups, donor livers were treated with the same ET receptor antagonists in vitro at the beginning of hypothermic preservation. A minimum of 6 animals was included in each group. Two hours after OLT, the hepatic microcirculation was investigated by intravital fluorescence microscopy. FITC-labelled erythrocytes were administered to measure functional sinusoidal density (FSD) and Ho33342 to visualise viable and
apoptotic cells in the liver. Blood was taken to measure plasma AST and ALT. Results: Untreated OLT recipients had a 50% reduction in FSD, a 20-fold increase in liver apoptotic cells and a 20-fold increase in plasma AST and ALT levels. Graft treatment in vitro with ETAR and ETAR/ETBR antagonists significantly improved FSD, reduced the number of apoptotic cells in the newly implanted liver and reduced plasma AST and ALT levels. Donor pre-treatment with ETAR, ETBR and ETAR/ETBR antagonists all significantly reduced plasma AST and ALT levels and apoptosis and improved microcirculatory flow in the liver. Conclusions: Donor pre-treatment with endothelin receptor A and B antagonists alone or in combination ameliorated post-OLT microcirculatory derangement and reduced liver injury following prolonged hypothermic preservation as effectively as graft treatment. Donor pre-treatment with endothelin antagonists may well have therapeutic potential in liver transplantation. Acknowledgements: The financial support from the Stanley Thomas Johnson Foundation and the New Zealand Lotteries Board is gratefully acknowledged.
O1B. Liver transplantation/surgery/acute liver failure- (b) Clinical
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LIVER TRANSPLANTATION FOR H C V - A L C O H O L AETIOLOGY: IS THE O U T C O M E SIMILAR TO THOSE TO HCV OR A L C O H O L A L O N E ?
V. Aguilerm M. Berenguer, S. Benlloch, M. Prieto, J. Berenguer.
Hepatology Department/Hospital La Fe, Valencia, Spain While recent data have shown a worse post-transplantation outcome in HCV-infected patients compared to uninfected recipients, there are no data regarding differences in those with mixed etiology (HCV+alcohol). Aims: to analyse whether post-transplantation outcome (survival, metabolic complications, histology) is different in patients transplanted for HCV+alcohol cirrhosis (n 39) vs HCV cirrhosis (n 193) or alcohol cirrhosis (n 65). Methods: comparison of survival, rate of metabolic complications (diabetes, hypertension, hyperlipidemia), significant alcohol intake, and one-year histologic disease (relevant disease: F~> 1) between HCV vs HCV+alcohol or alcohol vs alcohol-HCV patients transplanted between 1997 and 2001. Results: Baseline characteristics: Alcohol vs HCV+alcohol: hepatocellular carcinoma: 9% vs 26% (p 0.02), cyclosporine induction: 92% vs 60% (p 0.001); donor age: 43 (16 76) vs 51 (19 75) (p 0.04); prednisone duration: 393 (0 846) vs 310 (0 649) (p 0.02). HCV vs HCV+alcohol: age: 58 (28 68) vs 50 (32 65) (p 0.001), Child@ugh: 8 (5 13) vs 9 (6 14) (p 0.002), male gender: 57% vs 92% (p 0.0001); cyclosporine induction: 43% vs 60% (p 0.0001). The remaining variables at baseline were similar between HCV+alcohol vs HCV or alcohol alone. Survival (lst and 5th year): Alcohol: 96% and 84%, HCV: 75% and 55%, mixed aetiology: 84% and 76%. (Alcohol vs mixed aetiology, p ns; HCV vs mixed aetiology, p 0.01.) Hypertension: Alcohol 61%, HCV 40%, mixed aetiology 56% (Alcohol and HCV vs mixed aetiology respectively, p ns). Diabetes mellitus: Alcohol 28%, HCV 25%, mixed aetiology 36% (Alcohol and HCV vs mixed aetiology respectively, p ns). Hyperlipidemia: Alcohol 38%, HCV 16%, mixed aetiology 28% (Alcohol and HCV vs mixed aetiology respectively, p ns). Significant alcohol intake: Alcohol 10%, HCV 2%, mixed aetiology 3% (Alcohol and HCV vs mixed aetiology respectively; p ns). Relevant histologic disease (lst year): Alcohol 28%, HCV 61%, mixed aetiology 67% (Alcohol vs mixed aetiology p 0.005,
O1B. Liver transplantation~surgery~acute liver failure HCV vs mixed aetiology p ns). Rejection: Alcohol 11%, HCV 22%, mixed aetiology 13% (Alcohol and HCV vs mixed aetiology respectively, p ns). Conclusions: Relevant histologic disease was similar between HCV vs mixed aetiology. However, survival was lower. This fact suggests a more agresive disease in patients with HCV cirrhosis alone. Probably, in patients with mixed aetiology, pre-transplant alcohol was the determinant factor for hepatic progression. Metabolic complications and rejection were similar between groups.
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ACUTE LIVER FAILURE IN SCOTLAND - THIRTEEN Y E A R OBSERVATIONAL STUDY
C.M. Bates, J.S. Davidson, K.J. Simpson. Seottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinbu@, Scotland, UK Acute or fulminant hepatic failure (FHF) is a rare, life-threatening condition with no specific treatment except liver transplant. Paracetamol is the commonest cause of FHF in the UK. Legislative changes to paracetamol packaging were introduced in 1998 in order to reduce the number of overdoses and the prevalence of FHE The incidence, causes or outcomes of FHF in Scotland are unknown. A prospectively collected database was analysed to obtain information on patients admitted to the Scottish Liver Transplant Unit (SLTU) with FHE Between November 1992 and November 1st 2005 there have been 783 admissions to SLTU with FHE 351 males (45%) and 432 (55%) females. 563 (71.9%) patients had taken a paracetamol overdose (POD). Other causes included Non A E hepatitis 59 (7.5%), idiosyncratic drug reactions 36 (4.6%), Budd Chiari syndrome 15 (2.0%) and ischaemic hepatitis 14 (1.8%). 157 PODS (27.9%) met poor prognostic criteria, 84 (53.5%) were considered transplant candidates and 41 (49%) died prior to transplant. In patients with non-POD FHF more patients met poor prognostic criteria (85 patients, 38.6%), more were candidates (76 patients, 89%) and 57 patients (75%) survived to transplant. Paracetamol was taken as a staggered overdose in 140 (24.9%) cases associated with increased morbidity and greater percentage of patients being too sick for transplant [22 patients (56%) were candidates, 64% became too sick]. Mortality was increased with staggered mortality 34.3% vs non-staggered mortality 21.8%. The legislative changes have not significantly decreased admissions to SLTU (275 admissions Nov 1992 Sept 1998 compared with 285 admissions Oct 1998 Nov 2005). Increased numbers of patients met KCH criteria for poor prognosis (25% Nov 1992 Sept 1998 vs 30.5% Oct 1998 Nov 2005). There is a significant increase in patients with staggered overdose following legislation changes (43 patients Nov 1992 Sept 1998 vs 97 patients Oct 1998 Nov 2005). Paracetamol overdose remains the commonest reason for admission to SLTU. Legislative changes have not significantly reduced the number of admissions or deaths. Staggered overdoses have increased since the legislative change and are associated with poorer prognosis.
(b) Clinical
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~THE FIVE Y E A R FOLLOW-UP OF A RANDOMIZED STUDY COMPARING LAMIVUDINE WITH LAMIVUDINE+HBIg INVESTIGATING THE PREVENTION OF HBV R E C U R R E N C E AFTER LIVER TRANSPLANTATION M. Butil, A. Mas 2, M. Prieto 3, F. Casafont4, A. Gonzalez 5, M. Miras 6, J.I. Herreo 7, R. Jardi 1, A. Valdes 1, R. Esteban 1. 1Hospital General
Universitari ValM'Hebron, Barcelona, Spain," 2Institut de Malaties Digestives, Barcelona, Spain," 3Hospital General Universitario La Fd Valencia, Spain," 4Hospital Universitario Marquds de VaMecilla, Santander, Spain," 5Hospital Ntra. Sra de la Candelaria, Tenerife, Spain," 6Hospital Universitario Virgen de la Arrixaca, Murcia, Spain," 7Cl{nica Universitaria de Navarra, Spain Lamivudine monotherapy after a short course of HBIg and lamivudine has been proved useful in the prevention of HBV recurrence after LTx. Aim: To compare the long-term efficacy of two strategies (LAM vs LAM +HBIg) in preventing HBV recurrence after LTx. Patients and Methods: 29 LTx patients with HBV DNA levels <105 copies/mL at the time of LTx were randomized to receive prophylaxis with either Lam 100mg/daily or Lam+HBIg (2000UI/im/monthly) for 17 months after 1 month of LAM+HBIg. At month 18, the study was opened allowing patients to be treated with either lamivudine or combination therapy indefinitely. The primary efficacy end-point was the absence of HBsAg. Results: Fifteen patients were randomized to receive HBIg+LAM and 14 LAM until month 18 and then 20 continued with LAM alone and 9 with HBIg and LAM. After a follow-up of 5 years, the survival rate was 90%. Three patients died (2 from causes unrelated to HBV at month 36 and 60 and 1 from acute rejection and HBV recurrence at month 24). HBV recurrence was observed in 4 (18%) patients under long-term lamivudine therapy, including the patient who died. HBsAg positive at months 23, 24, 44 and 48. Two had been treated until month 18 with LAM and 2 with HBIg+LAM. HBV recurrence was observed as an acute hepatitis in two cases and as a mild asymptomatic disease in 2 cases. Recurrence was associated with bad therapy compliance in 3 cases and LAM resistance in another. Adefovir therapy was added to lamivudine in 3 cases and HBV DNA became undetectable. Besides, low levels of HBV DNA by PCR were detected in 22% of cases with HBsAg negative in the follow-up period. Conclusions: (1) The 5-year survival rate after LTx for HBV patients under prophylaxis with HBIg and LAM or LAM alone was 90%. (2) In spite of a short course of HBIg and LAM and long-term LAM prophylaxis 13% of patients had late HBV recurrence due to bad therapy compliance or lamivudine resistance. (3) Continuous monitoring permits early diagnosis of HBV recurrence and hence successful rescue therapy with adefovir.
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APPLICABILITY AND SAFETY OF E X T R A C O R P O R E A L LIVER S U P P O R T USING ALBUMIN DIALYSIS (MARS) IN THE SETTING OF LIVER TRANSPLANTATION
M.-V. Catalinm C. Ripoll, G. Clemente, M. Salcedo, D. Rincon, A. Matilla, O. Nufiez, I. Beceiro, O. Lo Iacono, R. Bafiares. Liver Transplantation
Unit, Hospital General Universitario Gregrorio Marathon, Madrid, Spain MARS is an extracorporeal device that supports hepatic and renal function in patients with acute (ALF) and acute on chronic liver failure (ACLF). Clinical experience in liver transplantation (LT) is still limited. Aim: To assess the applicability and safety of MARS in patients with ALF as a bridge to LT and in LT to support graft function or to treat intractable pruritus. Methods: From February 2002 to November 2005 23 patients were treated with MARS as a bridge to LT (n 7) (group I), with severe liver dysfunction during the first month after LT (n 9) (group II) or with intractable pruritus in LT (n 7) (group III). Mean age 52.5 years (range
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CORTICOSTEROIDS (DEXAMETHASONE, DEX) INHIBIT INTERFERON A L P H A (IFN) P R O D U C T I O N A N D SIGNALING VIA THE JAK-STAT PATHWAY
S. Khatkar, E.L. Renner. Section of Hepatology, Department of Medicine,
University of Manitoba, Winnipeg, MB, Canada Background and Aim: IFN signaling via the J a ~ S t a t pathway plays a pivotal role in eliciting an antiviral state in HCV infected hepatocytes (Blindenbacher A, Gastroenterology 2003). Chronic hepatitis C virus (HCV) related end-stage liver disease is the single most common indication for liver transplantation (OLT) worldwide. After OLT, HCV re-infection of the graft is universal, associated with a 10 100-fold increase in HCV viremia, responds poorly to IFN-based therapy and follows an aggressive course leading to graft cirrhosis in ~25% of patients within a few years. Use of (high dose bolus) corticosteroids has been repeatedly found to be associated with accelerated progression (Beringuer M, J Hepatol 2005). We hypothesized that corticosteroids interfere with IFN production and/or signaling. Methods: 1Mio peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers (Ficoll-Hypaque gradient centrifugation) were cultured (48h) in the presence/absence of l u M DEX and stimulated (last 24h) with 100ug/ml of the viral mimetic poly(inosinic acid) poly(cytidylic acid) (PolyIC); IFN content of supernatant was analyzed by ELISA. C57BL/6 mice were treated for 5 days with 10mg/kg i.p. DEX/vehicle daily and injected (tail vein) with 1000 U/gb.w. IFN/vehicle 20 min prior to harvesting the livers. Liver nuclear extracts were analyzed for Stat binding by electromobility shift assay (EMSA) using a consensus sequence IFN sensitive response element. The specificity of the signal was confirmed by supershift using a monoclonal Stat 1 antibody. Results: In the absence of DEX, IFN production by PBMCs of 4 volunteers was stimulated by PolyIC from median 17 (range 9 20) to 30 (26 37) pg/ml (p <0.01); in the presence of DEX, it remained below detection limit with and without PolyIC stimulation (both p vs. absence of DEX <0.01). DEX pretreatment virtually abolished the IFN-induced EMSA signal in nuclear extracts of mouse liver (n 4 per group). Conclusion: The corticosteroid DEX inhibits (a) IFN production by PBMCs of healthy volunteers and (b) IFN-induced Jak Stat signaling in mouse liver. While the underlying mechanisms remain to be elucidated, this is consistent with corticosteroids blunting the IFN-induced antiviral state and may pertain to the increased HCV viremia/accelerated course and the poor response to IFN-based therapy of recurrent hepatitis C after OLT.
I•
ENDOTHELIN ANTAGONIST TREATMENT IN LIVER TRANSPLANTATION: D O N O R OR GRAFT?
X.-Y. Zhang, A.M. Wheatley. 1Department of Physiology, University of
Otago, Dunedin, New Zealand Background and Objective: Here we tested the hypothesis that donor pre-treatment with endothelin receptor antagonists in vivo is as effective as graft pre-treatment in vitro in the protection of the transplanted graft from hypothermic ischaemi~reperfusion (I R) injury. Methods: OLT with graft rearterialisation was performed in male Lewis under ether anaesthesia. The graft was stored in U W solution at 4~ for 17 hr prior to implantation. Donors were injected with an endothelin A receptor (ETAR) (ABT-627, 5 mg/kg), an ETBR antagonist (A192621.1, 6 mg/kg), both ETAR/ETBR antagonists or saline, 30 min prior to graft retrieval. In separate groups, donor livers were treated with the same ET receptor antagonists in vitro at the beginning of hypothermic preservation. A minimum of 6 animals was included in each group. Two hours after OLT, the hepatic microcirculation was investigated by intravital fluorescence microscopy. FITC-labelled erythrocytes were administered to measure functional sinusoidal density (FSD) and Ho33342 to visualise viable and
apoptotic cells in the liver. Blood was taken to measure plasma AST and ALT. Results: Untreated OLT recipients had a 50% reduction in FSD, a 20-fold increase in liver apoptotic cells and a 20-fold increase in plasma AST and ALT levels. Graft treatment in vitro with ETAR and ETAR/ETBR antagonists significantly improved FSD, reduced the number of apoptotic cells in the newly implanted liver and reduced plasma AST and ALT levels. Donor pre-treatment with ETAR, ETBR and ETAR/ETBR antagonists all significantly reduced plasma AST and ALT levels and apoptosis and improved microcirculatory flow in the liver. Conclusions: Donor pre-treatment with endothelin receptor A and B antagonists alone or in combination ameliorated post-OLT microcirculatory derangement and reduced liver injury following prolonged hypothermic preservation as effectively as graft treatment. Donor pre-treatment with endothelin antagonists may well have therapeutic potential in liver transplantation. Acknowledgements: The financial support from the Stanley Thomas Johnson Foundation and the New Zealand Lotteries Board is gratefully acknowledged.
O1B. Liver transplantation/surgery/acute liver failure- (b) Clinical
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LIVER TRANSPLANTATION FOR H C V - A L C O H O L AETIOLOGY: IS THE O U T C O M E SIMILAR TO THOSE TO HCV OR A L C O H O L A L O N E ?
V. Aguilerm M. Berenguer, S. Benlloch, M. Prieto, J. Berenguer.
Hepatology Department/Hospital La Fe, Valencia, Spain While recent data have shown a worse post-transplantation outcome in HCV-infected patients compared to uninfected recipients, there are no data regarding differences in those with mixed etiology (HCV+alcohol). Aims: to analyse whether post-transplantation outcome (survival, metabolic complications, histology) is different in patients transplanted for HCV+alcohol cirrhosis (n 39) vs HCV cirrhosis (n 193) or alcohol cirrhosis (n 65). Methods: comparison of survival, rate of metabolic complications (diabetes, hypertension, hyperlipidemia), significant alcohol intake, and one-year histologic disease (relevant disease: F~> 1) between HCV vs HCV+alcohol or alcohol vs alcohol-HCV patients transplanted between 1997 and 2001. Results: Baseline characteristics: Alcohol vs HCV+alcohol: hepatocellular carcinoma: 9% vs 26% (p 0.02), cyclosporine induction: 92% vs 60% (p 0.001); donor age: 43 (16 76) vs 51 (19 75) (p 0.04); prednisone duration: 393 (0 846) vs 310 (0 649) (p 0.02). HCV vs HCV+alcohol: age: 58 (28 68) vs 50 (32 65) (p 0.001), Child@ugh: 8 (5 13) vs 9 (6 14) (p 0.002), male gender: 57% vs 92% (p 0.0001); cyclosporine induction: 43% vs 60% (p 0.0001). The remaining variables at baseline were similar between HCV+alcohol vs HCV or alcohol alone. Survival (lst and 5th year): Alcohol: 96% and 84%, HCV: 75% and 55%, mixed aetiology: 84% and 76%. (Alcohol vs mixed aetiology, p ns; HCV vs mixed aetiology, p 0.01.) Hypertension: Alcohol 61%, HCV 40%, mixed aetiology 56% (Alcohol and HCV vs mixed aetiology respectively, p ns). Diabetes mellitus: Alcohol 28%, HCV 25%, mixed aetiology 36% (Alcohol and HCV vs mixed aetiology respectively, p ns). Hyperlipidemia: Alcohol 38%, HCV 16%, mixed aetiology 28% (Alcohol and HCV vs mixed aetiology respectively, p ns). Significant alcohol intake: Alcohol 10%, HCV 2%, mixed aetiology 3% (Alcohol and HCV vs mixed aetiology respectively; p ns). Relevant histologic disease (lst year): Alcohol 28%, HCV 61%, mixed aetiology 67% (Alcohol vs mixed aetiology p 0.005,
O1B. Liver transplantation~surgery~acute liver failure HCV vs mixed aetiology p ns). Rejection: Alcohol 11%, HCV 22%, mixed aetiology 13% (Alcohol and HCV vs mixed aetiology respectively, p ns). Conclusions: Relevant histologic disease was similar between HCV vs mixed aetiology. However, survival was lower. This fact suggests a more agresive disease in patients with HCV cirrhosis alone. Probably, in patients with mixed aetiology, pre-transplant alcohol was the determinant factor for hepatic progression. Metabolic complications and rejection were similar between groups.
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ACUTE LIVER FAILURE IN SCOTLAND - THIRTEEN Y E A R OBSERVATIONAL STUDY
C.M. Bates, J.S. Davidson, K.J. Simpson. Seottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinbu@, Scotland, UK Acute or fulminant hepatic failure (FHF) is a rare, life-threatening condition with no specific treatment except liver transplant. Paracetamol is the commonest cause of FHF in the UK. Legislative changes to paracetamol packaging were introduced in 1998 in order to reduce the number of overdoses and the prevalence of FHE The incidence, causes or outcomes of FHF in Scotland are unknown. A prospectively collected database was analysed to obtain information on patients admitted to the Scottish Liver Transplant Unit (SLTU) with FHE Between November 1992 and November 1st 2005 there have been 783 admissions to SLTU with FHE 351 males (45%) and 432 (55%) females. 563 (71.9%) patients had taken a paracetamol overdose (POD). Other causes included Non A E hepatitis 59 (7.5%), idiosyncratic drug reactions 36 (4.6%), Budd Chiari syndrome 15 (2.0%) and ischaemic hepatitis 14 (1.8%). 157 PODS (27.9%) met poor prognostic criteria, 84 (53.5%) were considered transplant candidates and 41 (49%) died prior to transplant. In patients with non-POD FHF more patients met poor prognostic criteria (85 patients, 38.6%), more were candidates (76 patients, 89%) and 57 patients (75%) survived to transplant. Paracetamol was taken as a staggered overdose in 140 (24.9%) cases associated with increased morbidity and greater percentage of patients being too sick for transplant [22 patients (56%) were candidates, 64% became too sick]. Mortality was increased with staggered mortality 34.3% vs non-staggered mortality 21.8%. The legislative changes have not significantly decreased admissions to SLTU (275 admissions Nov 1992 Sept 1998 compared with 285 admissions Oct 1998 Nov 2005). Increased numbers of patients met KCH criteria for poor prognosis (25% Nov 1992 Sept 1998 vs 30.5% Oct 1998 Nov 2005). There is a significant increase in patients with staggered overdose following legislation changes (43 patients Nov 1992 Sept 1998 vs 97 patients Oct 1998 Nov 2005). Paracetamol overdose remains the commonest reason for admission to SLTU. Legislative changes have not significantly reduced the number of admissions or deaths. Staggered overdoses have increased since the legislative change and are associated with poorer prognosis.
(b) Clinical
$57
~THE FIVE Y E A R FOLLOW-UP OF A RANDOMIZED STUDY COMPARING LAMIVUDINE WITH LAMIVUDINE+HBIg INVESTIGATING THE PREVENTION OF HBV R E C U R R E N C E AFTER LIVER TRANSPLANTATION M. Butil, A. Mas 2, M. Prieto 3, F. Casafont4, A. Gonzalez 5, M. Miras 6, J.I. Herreo 7, R. Jardi 1, A. Valdes 1, R. Esteban 1. 1Hospital General
Universitari ValM'Hebron, Barcelona, Spain," 2Institut de Malaties Digestives, Barcelona, Spain," 3Hospital General Universitario La Fd Valencia, Spain," 4Hospital Universitario Marquds de VaMecilla, Santander, Spain," 5Hospital Ntra. Sra de la Candelaria, Tenerife, Spain," 6Hospital Universitario Virgen de la Arrixaca, Murcia, Spain," 7Cl{nica Universitaria de Navarra, Spain Lamivudine monotherapy after a short course of HBIg and lamivudine has been proved useful in the prevention of HBV recurrence after LTx. Aim: To compare the long-term efficacy of two strategies (LAM vs LAM +HBIg) in preventing HBV recurrence after LTx. Patients and Methods: 29 LTx patients with HBV DNA levels <105 copies/mL at the time of LTx were randomized to receive prophylaxis with either Lam 100mg/daily or Lam+HBIg (2000UI/im/monthly) for 17 months after 1 month of LAM+HBIg. At month 18, the study was opened allowing patients to be treated with either lamivudine or combination therapy indefinitely. The primary efficacy end-point was the absence of HBsAg. Results: Fifteen patients were randomized to receive HBIg+LAM and 14 LAM until month 18 and then 20 continued with LAM alone and 9 with HBIg and LAM. After a follow-up of 5 years, the survival rate was 90%. Three patients died (2 from causes unrelated to HBV at month 36 and 60 and 1 from acute rejection and HBV recurrence at month 24). HBV recurrence was observed in 4 (18%) patients under long-term lamivudine therapy, including the patient who died. HBsAg positive at months 23, 24, 44 and 48. Two had been treated until month 18 with LAM and 2 with HBIg+LAM. HBV recurrence was observed as an acute hepatitis in two cases and as a mild asymptomatic disease in 2 cases. Recurrence was associated with bad therapy compliance in 3 cases and LAM resistance in another. Adefovir therapy was added to lamivudine in 3 cases and HBV DNA became undetectable. Besides, low levels of HBV DNA by PCR were detected in 22% of cases with HBsAg negative in the follow-up period. Conclusions: (1) The 5-year survival rate after LTx for HBV patients under prophylaxis with HBIg and LAM or LAM alone was 90%. (2) In spite of a short course of HBIg and LAM and long-term LAM prophylaxis 13% of patients had late HBV recurrence due to bad therapy compliance or lamivudine resistance. (3) Continuous monitoring permits early diagnosis of HBV recurrence and hence successful rescue therapy with adefovir.
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APPLICABILITY AND SAFETY OF E X T R A C O R P O R E A L LIVER S U P P O R T USING ALBUMIN DIALYSIS (MARS) IN THE SETTING OF LIVER TRANSPLANTATION
M.-V. Catalinm C. Ripoll, G. Clemente, M. Salcedo, D. Rincon, A. Matilla, O. Nufiez, I. Beceiro, O. Lo Iacono, R. Bafiares. Liver Transplantation
Unit, Hospital General Universitario Gregrorio Marathon, Madrid, Spain MARS is an extracorporeal device that supports hepatic and renal function in patients with acute (ALF) and acute on chronic liver failure (ACLF). Clinical experience in liver transplantation (LT) is still limited. Aim: To assess the applicability and safety of MARS in patients with ALF as a bridge to LT and in LT to support graft function or to treat intractable pruritus. Methods: From February 2002 to November 2005 23 patients were treated with MARS as a bridge to LT (n 7) (group I), with severe liver dysfunction during the first month after LT (n 9) (group II) or with intractable pruritus in LT (n 7) (group III). Mean age 52.5 years (range