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972A AASLD ABSTRACTS HEPATOLOGY, October, 2015 is highly effective in preventing HBV recurrence. With current preferred antivirals (high barrier to resistance), more patients are likely to have such a profile and utilizing an individualized approach to HBIG prophylaxis offers a better balance between prophylaxis costs and prevention of HBV recurrence. ULN: 575.0 vs 127.9; ALT
HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 973A ily was detected by Western blot, and the DNA binding level of hepatocyte nuclear factor 4α(HNF4α) was detected by EMSA. Summary: Luteolin decreased the levels of HBsAg and HBeAg and the HBV DNA load both in the cultured medium and in serum, and it also suppressed the HBV DNA RI and the expression of HBsAg and HBcAg, which demonstrated that luteolin can effectively inhibit HBV replication both in vitro and in vivo. In addition, luteolin effectively downregulated the expression of HNF4α and decreased its binding level with HBV preC/C promoter in HepG2.2.15 cells. The extracellular signal-regulated kinase(ERK) and c-Jun N-terminal kinase(JNK) signal pathways, but not the p38 signal pathway in the MAPK family, were activated by luteolin, which can be blocked by their inhibitors, respectively. However, it was the ERK inhibitor(U0126) rather than the JNK inhibitor(SP600125) can attenuate the down-regulation of HNF4α by luteolin and restore the protein level of HNF4α. In addition, blocking the ERK pathway with inhibitor can cripple the inhibition of HBV replication by luteolin, while blocking the JNK pathway do not affect the inhibitory effect of luteolin on HBV replication. Conclusions: Luteolin inhibits HBV replication through down-regulating HNF4α expressin via activating ERK signal pathway. Keywords: luteolin; hepatitis B virus; replication; hepatocyte nuclear factor 4α; extracellular signal-regulated kinase Disclosures: The following authors have nothing to disclose: Yunhong Nong, Ying Shi, Miao Liu, Libo Yan, Yong Lin, Lang Bai, Hong Tang 1563 Redefining the Natural History of Chronic Hepatitis B: Using Viral Diversity to Classify Disease and Predict Serological Response to Nucleos(t)ide Analogue (NA) Therapy Julianne Bayliss 1 , Gillian Rosenberg 1 , Lilly Yuen 1 , Anuj Gaggar 2 , Kathryn M. Kitrinos 2 , Mani Subramanian 2 , Edward J. Gane 3 , Henry Lik-Yuen Chan 4 , Rachel Hammond 1 , Scott Bowden 1 , Peter A. Revill 1 , Stephen Locarnini 1 , Alex J. Thompson 5 ; 1 Molecular R&D, VIDRL, Melbourne, VIC, Australia; 2 Gilead Sciences, Foster City, CA; 3 New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; 4 Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong; 5 Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia Background The presence of basal core promoter (BCP) and precore (PC) mutations in immune tolerant (IT) patients with chronic hepatitis B (CHB) suggests a transition between IT and immune clearance (IC) disease. Here, next generation sequencing (NGS) was used to analyse the impact of baseline viral diversity on CHB natural history and its association with baseline serology and response to NA treatment. Methods GS-US-203-0101 and GS-US-174-0103 evaluated tenofovir DF (TDF) containing regimens in IT and IC patients, respectively. Only genotype B/C patients were included (B= 83; C= 102). Patients were classified as True IT (ALT 20-40-80IU/mL). Viral diversity, defined as non-synonymous (NS), genotype specific viral substitutions from wild type (WT) and entropy scores across the whole genome (WG), were calculated using Illumina MiSeq NGS and correlated with baseline clinical and virological data and W192 serological response. Results 185 patients were analysed (baseline: median age 32yrs, 55% male; median ALT 29 IU/mL, HBV DNA 8.38 log 10 IU/mL, HBsAg 51,590 IU/mL, HBeAg 3,358 PEIU/mL). Increased viral diversity was associated with lower HBV DNA (p= 0.001), HBeAg (p< 0.0001) and HBsAg (p< 0.0001) titres and higher ALT levels (p< 0.0001). Although HBV DNA, HBeAg and HBsAg titres did not differ significantly between True IT and Late IT patients (Table 1), a significantly higher percentage of Late IT patients had BCP and PC mutations (p= 0.001 and p< 0.0001, respectively). Late IT patients also had more NS substitutions (p= 0.001), higher entropy scores (p= 0.002), and were more likely to achieve HBeAg seroconversion by W192 compared to True IT patients (True IT= 3%, Late IT= 14%, p< 0.0001). Discussion There is a subset of IT CHB patients with a virological profile similar to IC patients. This subset of patients may be transitioning between IT and IC disease and are more likely to respond favourably to TDF therapy. Disclosures: Julianne Bayliss - Grant/Research Support: Gilead Inc. Gillian Rosenberg - Grant/Research Support: Gilead Sciences Anuj Gaggar - Employment: Gilead Sciences, Inc. Kathryn M. Kitrinos - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Mani Subramanian - Employment: Human Genome Sciences, Human Genome Sciences, Human Genome Sciences, Human Genome Sciences; Stock Shareholder: Human Genome Sciences, Human Genome Sciences, Human Genome Sciences, Human Genome Sciences Edward J. Gane - Advisory Committees or Review Panels: Novira, AbbVie, Janssen, Gilead Sciences, Janssen Cilag, Achillion, Merck, Tekmira; Speaking and Teaching: AbbVie, Gilead Sciences, Merck Henry Lik-Yuen Chan - Advisory Committees or Review Panels: Gilead, MSD, Bristol-Myers Squibb, Roche, Novartis Pharmaceutical, Abbvie; Speaking and Teaching: Echosens Peter A. Revill - Grant/Research Support: Gilead Sciences Stephen Locarnini - Consulting: Gilead, Arrowhead; Employment: Melbourne Health Alex J. Thompson - Advisory Committees or Review Panels: Gilead, Abbvie, BMS, Merck, Spring Bank Pharmaceuticals, Arrowhead, Roche; Grant/Research Support: Gilead, Abbvie, BMS, Merck; Speaking and Teaching: Roche, Gilead, Abbvie, BMS The following authors have nothing to disclose: Lilly Yuen, Rachel Hammond, Scott Bowden 1564 Angiopoetin-like protein 2 independently associated with liver inflammation and fibrosis in patients chronically infected with hepatitis B virus Hong Zhao, Yong-Qiong Deng, Gui-Qiang Wang; Department of infectious disease, Peking University First Hospital, Beijing, China Background: Guidelines recommend antiviral therapy for HBeAg(+)patients with HBV DNA >=20000IU/ml or HBeAg(-) patients with HBVDNA >=2000IU/ml, and alanine aminotransferase (ALT) levels more than 2 times of upper limit of normal (ULN). For patients who don’t meet the criteria above, therapy decision depends on hepatic histology, an invasive process. The available non-invasive assessments could only predict the stages of liver fibrosis. Therefore, a non-invasive method or biomarker predicting moderate and more inflammation or significant fibrosis is urgently needed. Angiopoetin-like protein 2 (Angptl2) is a mediator of chronic inflammation contributing to extracellular matrix remodeling. Aim: The aim of the study was to explore the predicting value of serum angptl2 for moderate
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1312A AUTHOR INDEX HEPATOLOGY, Octo
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