P.J. Thuluvath, H.Y. Yoo, Department Of Medicine, The Johns Hopkins University School Of Medicine, Baltimore, MD, USA

Anecdotal experience also shows that LDLT recipients with HCV may have a poor outcome. Objective: To analyze the outcomes of LDLT and compare the results to a matched population who received cadaver liver transplant (CLT) using UNOS data. Patients & Methods: For each LDLT recipients (n=764), two CLT recipients (case-controls, n=1470), matched for age, sex and diagnosis, were selected from the UNOS data. Results: As per study design, both groups had similar age, sex and etiology. 2.5% (n=19) of the recipients had previous liver transplantation, and there was no multi-organ transplantation along with LDLT. Recipients of LDLT had more stable liver disease as shown by fewer patients with UNOS status 1, in ICU or with life support. Creatinine and cold ischemia time were higher in the CLT groups. Incidence of primary graft non-function and 2-year Kaplan-Meier survival was similar in both groups (79.0% in LDLT vs. 80.7% in case-controls, p=0.56). 2-yr graft survival was lower in LDLT (64.4% vs. 73.3%, p <0.001). Cox regression (after adjusting for confounding variables) showed a significantly lower graft (HR 1.6) survival in LDLT. HCV positive LDLT recipients showed lowest graft survival when compared to non-HCV LDLT recipients or HCV patients who received CLT. Conclusion: LDLT recipients are less sick than CLT recipients. Although 2-year patient survival in LDLT is similar to a matched population who received CLT, 2-year graft survival was significantly lower in LDLT recipients. HCV recipients who had LDLT had a poor survival compared to either CLT recipients with HCV or non-HCV LDLT recipients.

A RANDOMISED DOUBLE-BLIND PHASE II STUDY OF LAMIVUDINE (LAM) COMPARED TO LAMIVUDINE PLUS ADEFOVIR DIPIVOXIL (ADV) FOR TREATMENT NAìVE PATIENTS WITH CHRONIC HEPATITIS B (CHB) : WEEK 52 ANALYSIS

	J.J.Y. Sung, 1 J.Y. Lai, 2 S. Zeuzem, 3 W.C. Chow, 4 E. Heathcote, 5 R. Perrillo, 6 C. Brosgart, 7 M. Woessner, 8 S.A. Scott, 9 F.M. Campbell, 9 Presenting Author 1Prince Of Wales Hosp, Hong Kong, 2Princess Margaret Hosp, Hong Kong, China 3Univ Hosp, Hamburg, Germany 4Singapore General Hosp, Singapore, 5Toronto Western Hosp, ON, Canada 6Alton L.Oschner Clinic, LA, USA 7Gilead Sciences Inc., CA, USA 8GlaxoSmithKline, NC, USA 9GlaxoSmithKline, Middlesex, UK Background: Both LAM and ADV have proven efficacy and safety in CHB patients. In vitro data suggest they have additive/synergistic activity and may be more effective in combination for treatment-na•ve CHB patients. Methods: 115 patients were randomised to LAM (100mg od) and ADV (10mg od) or LAM and ADV-placebo (PLA) for 104 weeks. Primary-endpoint was HBV-DNA time-weighted average change from baseline to W16 (DAVG16). Secondary-endpoints included: ALT-normalisation, HBV-DNA reduction, HBeAg/HBsAg loss, incidence of viral-breakthrough and YMDD mutant HBV. Results: Groups were similar at baseline. Of 112 patients, mean age 36-years, 79% male, 64% Asian, 34% Caucasian, 96% HBeAg-positive, 96% ALT>ULN, 98% HBV-DNA positive (Roche-COBAS). (insert table here) LAM monotherapy had a significantly higher incidence of ALT-normalisation at W48 and W52. However, median ALT was similar in both groups throughout Year-1. Both regimens were well tolerated with similar safety profiles. Serious AEÕs: 4/55 (7%) in LAM and 1/58 (2%) in LAM+ADV group.Conclusions: During Year-1, LAM+ADV did not enhance the antiviral, biochemical or serological outcome compared to LAM in treatment-na•ve CHB patients. An increased incidence of YMDD mutant HBV and viral-breakthrough was observed in the LAM group. Clinical benefit of LAM+ADV may not become apparent until Year-2.

SIMVASTATIN AMMELIORATES THE INCREASED HEPATIC VASCULAR TONE IN PATIENTS WITH CIRRHOSIS

	C. Zafra, J.G. Abraldes, C. Cortez, A. Berzigotti, I. Tarantino, J.C. Garcia-Pagan, J. Bosch, Presenting Author Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic. IDIBAPS. University Of Barcelona., Barcelona, Spain An insufficient intrahepatic production of NO in cirrhotic liver contributes to increase hepatic resistance and portal hypertension, and enhances the postprandial increase in portal pressure. Simvastatin increases NO production by enhancing AKT-dependent eNOS phosphorylation. Therefore, simvastatin may decrease hepatic resistance in cirrhosis. This was evaluated in a group of patients with cirrhosis and portal hypertension. Methods: Protocol 1. 13 patients had measurements of mean arterial pressure, cardiac output, systemic vascular resistance, HVPG and hepatic blood flow (HBF) before and 30 and 60 min after receiving 40 mg of simvastatin. Protocol 2. 17 patients were randomized to receive placebo or simvastatin (40mg) 12 h and 1 h before the study. After baseline measurements, a standard liquid meal was given and measurements were repeated at 15, 30 and 45 min. Results: Protocol 1. Acute simvastatin did not modify HVPG but increased HBF (+21± 13% and +14± 23% at 30 and 60 min respectively;p=0.04) and decreased estimated hepatic sinusoidal resistance by 14±11% and 11±17% (p=0.01). Systemic hemodynamics were not modified. Protocol 2. With respect to placebo, pretreatment with simvastatin significantly attenuated the postprandial increase in portal pressure (+8±8% vs +17±7% at 15 min, +6±6% vs +18±8% at 30 min, +8±9 vs +15±8% at 45 min;p=0.03). HBF increased equally in the two groups. Hepatic resistance decreased in simvastatin group but not in placebo (-17±10% vs -5±8% at 30 min;p=0, 03). Conclusions: Simvastatin effectively decreases hepatic resistance in patients with cirrhosis, without deleterious effects on systemic circulation.