General Session 2 & Awards' 1 $21 2. Both treatments reduced serum HBV-DNA levels during therapy, with a significantly higher mean reduction in HBV-DNA levels at EOT in the PEG-IFN ~-2b group compared with the IFN ~-2b group (2.22 logl0 cps/mL vs 1.68 logl0 cps/mL; P 0.0283). 3. 26.09% patients had genotype B and 73.91% patients had genotype C. 4. Significantly more patients with genotype B than genotype C achieved sustained response in both groups (P < 0.05). More genotype C patients achieved sustained response in the PEG-IFN ~-2b group than the IFN ~-2b group (11.90% vs 3.49%, P 0.039). 5. Adverse event incidence was similar with PEG-IFN a-2b compared to IFN ~-2b (94.78% vs 95.65%). At EOT, discontinuations were less in the PEG-IFN ~-2b group (none) compared with the IFN ~-2b group (5.22%). EOT 24 weeks'follow-up PEG-IFNc~-2b IFNc~-2b PEG-IFNc~-2b IFNc~-2b (n 115) (n 115) (n 115) (n 115) HBV-DNA <105 copies/mL 43 (37.39%) 34 (29.56%) 34 (29.56%) 31 (26.96%) HBeAglossrate 26 (22.61%) 20 (17.39%) 28 (24.35%) 16 (13.91%) HBeAgseroconversion 25 (21.74%) 19 (16.52%) 19 (16.52%) 16 (13.91%) ALTnommlisation 59 (51.30%) 50 (43.48%) 50 (43.48%) 51 (44.35%) Conclusions: In China, PEG-IFN a-2b is an effective and well tolerated treatment for HBeAg + hepatitis B. There were significantly greater decreases in serum HBV-DNA levels at EOT, higher HBeAg-negative rates after 24 weeks' follow-up and more genotype C patients with sustained response in the PEG-IFN a-2b group than the IFN a-2b group. Genotype B was associated with a significantly better sustained therapy response than genotype C in both groups. • ] A MULTI-GENE SIGNATURE ACCURATELY PREDICTS THE RISK OF BRIDGING FIBROSIS/CIRRHOSIS IN PATIENTS WITH CHRONIC HEPATITIS C H. Huang 1, T.L. Wright2, R.C. Cheung3, T.J. Layden 4, S. Friedman 5, N. Bzowej 6, C. Cooper7, A. Jacobson1, R. Venkatesh 1, O.T. Abar 1, J. Chan 1, J.J. Catanese 1 , D.U. Leong 1, L. Yee2, T.J. White 1, J.J. Sninsky1, M. Shiffman8. 1Celera Diagnostics, Alameda, CA, USA," 2University of California, San Francisco, CA, USA," 3Stanford University, Stanford, CA, USA," 4University of Illinois, Chicago, IL, USA," 5Mount Sinai School of Medicine, New York, NY, USA," 6California Pacific Medical Cente~ San Francisco, CA, USA," 7The Ottawa Hospital General Campus, Ottawa, Canada," 8Virginia Commonwealth University, Richmond, VA, USA Background: Clinical risk factors such as gender, age at infection, alcohol consumption and obesity are poor predictors for fibrosis risk in HCV patients. Objective: To identify a panel of genetic markers, alone or in combination with clinical factors, which can accurately predict the risk of bridging fibrosis/cirrhosis in HCV patients. Methods: 1468 patients with chronic hepatitis C were enrolled from 5 Centers in the USA. A genomic scan of 20,573 gene-centric single nucleotide polymorphisms (SNPs) was performed in 537 samples from Center 1. 155 SNPs were selected for model building, including 119 'Replicated SNPs' associated with fibrosis risk in both Center-1 and Center-2 samples (N 487), and another 36 SNPs in the neighboring regions of several replicated SNPs. A multi-SNP signature was constructed in samples from Center 1 (Training set), using a correlation-based heuris- tics combined with Naive Bayes classifier. The signature was then validated in a Validation set independently enrolled from Centers 3, 4 and 5 (Total N 448). Results: A 39-SNP signature had a significant predictive value for the risk of bridging fibrosis/cirrhosis in Caucasian HCV patients. For predicting the risk of predisposition to bridging fibrosis/cirrhosis, the area under the ROC curves (AUC) was 0.95 in the Training set. In the Validation set, AUC was 0.71 (p 0.0005) using 39-SNP signature, 0.55 (p 0.48) using clinical risk factors (age, gender and daily alcohol), and 0.72 (p 0.0006) when combining 39-SNP and clinical risk factors. The results indicated that genetic markers are better predictors than clinical risk factors, and genetics alone can provide accurate prediction. In the Validation set, a cut-off of genetic risk index at 0.25 (range, 0.00 1.00), had a 70% sensitivity and 79% specificity for the prognosis of the risk of bridging fibrosis/cirrhosis. Of the 39 SNPs, 13 were located in genes involved in the oxidative stress, inflammation, lipid metabolism, and matrix degradation in the fibrogenesis pathway. Conclusions: A panel of 39 SNPs can accurately predict the risk of bridging fibrosis/cirrhosis in Caucasian HCV patients. Such a test may improve the management of hepatitis C and the conduct of antifibrotic trials by identifying patients at high genetic risk for rapid fibrosis progression. [• CONTINUED VIROLOGIC AND BIOCHEMICAL IMPROVEMENT THROUGH 96 WEEKS OF ENTECAVIR TREATMENT IN HBeAg(-) CHRONIC HEPATITIS B PATIENTS (STUDY ETV-027) D. Shouvall~ U.S. Akarca 2, G. Hatzis 3, G. Kitis4, C.L. Lai 5, H. Cheinquer6, T.T. Chang 7, R. Zink 8, J. Zhu8, H. Brett-Smith8. 1Hadassah Medical Organization, Hadassah University Hospital, Jerusalem, Israel," 2Division of Gastroenterology, Ege University Faculty of Medicine, Izmir, Turkey," 3Department of Pathophysiology, Laikon General Hospital, Athens, Greece," 4Department of Gastroenterology, George Papanikolaou General Hospital of Thessaloniki, Greece," 5Department of Medicine, University of Hong Kong, Hong Kong SAR, China," 6 Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil," 7Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan," 8Bristol-Myers Squibb Company, Wallingford, CT, USA Background: Entecavir (ETV) demonstrated superior virologic, biochem- ical and histologic benefit compared to lamivudine (LVD) at week 48 in HBeAg( ) chronic hepatitis B (CHB) patients. HBV DNA suppression to <300 copies/mL occurred in 90% of ETV patients and 72% of LVD patients. Efficacy and safety through 96 weeks of treatment is reported here. Methods: 638 HBeAg( ) CHB patients were randomized 1:1 and treated with ETV 0.5mg (n 325) or LVD 100mg (n 313) for 1 year. At week 52, patient management decisions were made based on week 48 laboratory results: 85% (275/325) of ETV patients and 78% (245/313) of LVD patients achieved Response (HBV DNA <0.7 MEq/mL by bDNA assay and ALT < 1.25 • and discontinued therapy. Non-responders (HBV DNA />0.7MEq/mL) also discontinued therapy (3 ETV and 18 LVD patients). Eleven percent in both treatment groups (ETV 34/325, LVD 34/313) achieved Virologic Response (HBV DNA <0.7 MEq/mL but ALT/> 1.25 • and could continue blinded therapy through week 96. A cumulative response was confirmed when two sequential measurements or last on-treatment measurement for the endpoint occurred. Cumulative confirmed virologic and biochemical endpoints for all treated patients through week 96 ETV 0.5 mg LVD 100 mg p-value (n 325) (n 313) HBV DNA < 300 copies/mLby PCR (%) 94 77 <0.0001 ALT ~< 1• 89 84 >0.05 Results: 26 ETV and 28 LVD patients with Virologic Response continued to a second year of therapy. Of these, 96% of ETV-treated and 64% of