POSTERS DNA level at week 24 during Pegasys therapy may be used to predict response of Pegasys therapy. 551 RELATIONSHIP BETWEEN PRECORE/CORE PROMOTER MUTANTS, HBEAG LEVELS AND SEROLOGICAL RESPONSE IN HBEAG-POSITIVE CHRONIC HEPATITIS B TREATED WITH NUCLEOS(T)IDE ANALOGUES R. Zoutendijk 1 , M. Sonneveld 2 , J. Reijnders 2 , A. van Vuuren 2 , S. Pas 1 , B. Hansen 1 , A. Boonstra 2 , H. Janssen 2 . 1 Erasmus MC, 2 Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: r.zoutendijk@erasmusmc.nl Background: Precore (PC) and core promoter (BCP) mutations are the most prevalent naturally occurring variations of hepatitis B virus (HBV) and are thought to reduce the production of HBeAg. Moreover, patients with these mutations remain viraemic despite HBeAg seroconversion and are at risk for developing liver related complications. Methods: We investigated the influence PC/BCP mutants and their relation with HBeAg levels and HBeAg seroconversion in 138 HBeAg-positive patients treated with different nucleos(t)ide analogues. The presence of mutants was assessed at baseline by line probe assay (Innogenetics, Ghent, Belgium), HBeAg levels were measured by Elecsys (Roche). Median duration of therapy was 29 (IQR 18–56) months. Results: Patients were predominantly male (78%) and harbored genotypes A (33%), B (18%), C (16%), D (27%) or other (5%). Patients were treated with lamivudine (LAM, 38%), adefovir (ADV, 22%), entecavir (30%), tenofovir (TDF, 6%) and TDF/ADV-LAM (4%). Fifty- three (38%) patients had wildtype (WT) virus at baseline, 25 (18%) PC, 33 (24%) BCP and 27 (20%) had both PC and BCP mutants. Baseline HBeAg levels were different within these 4 groups: 2.68 (WT), 1.77 (PC), 1.81 (BCP) and 1.48 (both mutants) log U/mL respectively (p < 0.001) and HBeAg levels correlated with HBV DNA (r = 0.55; p < 0.001). HBeAg-seroconversion was achieved in 45 (33%) patients and HBsAg-seroconversion in 6 (4%) patients. In multivariate analysis, the presence of PC and/or BCP mutants (HR 2.30, p = 0.045), baseline HBV DNA (HR 0.82, p = 0.08) and ALT (HR 1.04, p = 0.02), but not HBeAg levels (p = 0.36) were independently associated with HBeAg seroconversion. Patients with PC mutants had a much lower probability of achieving HBV DNA <2000 IU despite HBeAg-seroconversion compared to patients without PC mutants (68% versus 100%, p = 0.003). Confirmed HBeAg relapse was more frequently noted in patients with BCP mutations (46% versus 19%, p = 0.06). Conclusions: Presence of PC/BCP mutants before NUC therapy was associated with lower levels of HBeAg and a higher probability of HBeAg seroconversion. However, presence of PC/BCP mutants also predisposed to persistent replication or HBeAg relapse after HBeAg seroconversion. 552 FINITE PEGINTERFERON RESULTS IN HIGHER SEROLOGICAL, BUT NOT VIROLOGICAL, RESPONSE RATES WHEN COMPARED TO CONTINUOUS ENTECAVIR IN HBEAG-POSITIVE CHRONIC HEPATITIS B R. Zoutendijk 1 , M. Sonneveld 1 , B. Hansen 2 , H. Janssen 2 . 1 Erasmus MC, 2 Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands E-mail: r.zoutendijk@erasmusmc.nl Background and Aims: Hepatitis B e Antigen (HBeAg) seroconversion and Hepatitis B surface Antigen (HBsAg) seroclearance confer an improved prognosis. Both endpoints are more often achieved with one year peginterferon (PEG- IFN) compared to one year of nucleos(t)ide analogues (NA), but prolonged NA therapy may result in serological response rates similar to those achieved with PEG-IFN. Materials and Methods: A total of 266 HBeAg-positive CHB patients were treated with PEG-IFN±lamivudine for one year and 91 NA- naïve patients were treated with prolonged entecavir (ETV). Follow- up was terminated in patients retreated with NA after PEG-IFN. Results: Median follow-up was 92 weeks (IQR 78–198) for PEG- IFN patients, and 92 (IQR 50–132) for ETV patients. Groups were balanced for HBV genotype, age, sex and previous IFN therapy. Baseline HBV DNA and ALT were higher in PEG-IFN patients (9.1 vs. 8.0 log copies/mL (p < 0.001) and 4.3 vs. 3.1×ULN (p = 0.004)). One- hundred-fourteen (32%) patients achieved HBeAg seroconversion after 78 weeks (IQR 52–120). The cumulative probability of HBeAg seroconversion was higher in PEG-IFN treated patients (p = 0.007). PEG-IFN was an independent determinant of HBeAg seroconversion in a Cox model; hazard rate (HR) for PEG-IFN versus ETV was 3.16 (95%CI: 1.57–6.36, p < 0.001), adjusted for HBV genotype, age, ALT and HBV DNA. Thirty (8%) patients cleared HBsAg in 92 (78–170) weeks. The cumulative probability of HBsAg loss was higher in patients receiving PEG-IFN (p = 0.032). PEG-IFN therapy was independently associated with HBsAg clearance, with a HR of 5.66 (95% CI: 0.76–42.40, p = 0.027) after adjustment for genotype, age and previous IFN. However, HBV DNA undetectability (HBV DNA <80 IU/mL) at week 78 (6 months post-treatment in patients treated with PEG-IFN) was only achieved in 8% of patients treated with PEG-IFN versus 77% for ETV (p < 0.001). At last follow-up evaluation (≥ week 78) HBV DNA undetectability was achieved in 15% of PEG-IFN treated patients versus 92% of patients on ETV (p < 0.001). Conclusions: PEG-IFN results in higher rates of HBsAg clearance, and thus sustained remission of CHB, than prolonged ETV therapy, also after adjustment for baseline factors. However, continuous ETV results in higher rates of virological suppression compared with PEG-IFN. 09. VIRAL HEPATITIS A AND E 553 RISK FACTORS ASSOCIATED WITH HEPATITIS A VIRUS (HAV) AND ALCOHOL RELATED LIVER DISEASE SEVERITY – A MOLECULAR DIAGNOSIS BASED STUDY FROM NORTHEAST INDIA M. Bose 1 , S. Bose 1 , A.K. Saikia 2 , B. Baruah 1 , S. Medhi 1 , A. Sarma 3 , M. Deka 1 . 1 Biotechnology, Gauhati University, 2 Medicine and Gastroenterology, Central Hospital, NF Railway, Maligaon, 3 Pathology, B.Borooah Cancer Institute, Guwahati, India E-mail: moumita_bose85@yahoo.co.in HAV infection, routine alcohol consumption critically influences liver disease burden in Northeast India, who are ethnically distinct, tribal dominated and of lower socio-economic status. Viral and alcohol mediated oxidative stress inducing DNA damage; altered DNA repair mechanism (BERpathway) influences disease severity. Polymorphic hOGG1 and XRCC1 genes, important enzymes participating in BER pathway, results in susceptibility to liver diseases and cancer. Aim: Evaluate the role of HAV genotype, hOGG1 and XRCC1 polymorphism, and 8-oxo-G levels in deciding the liver disease severity. Methods: Clinically proven and serologically correlated liver disease patients with jaundice {HAV-AVH = 54, HAV-FHF = 8, ALD = 28, Alcoholic-cirrhosis = 10} were enrolled with informed consent; along with age–sex matched community controls (n = 120). Paraffin embedded liver biopsy sections of 5 mm each were collected from Journal of Hepatology 2012 vol. 56 | S71–S224 S219