Hopefully, the initiation

Hopefully, the initiation Epacadostat cost of the World Health Organization International Clinical Trials Registry Platform will facilitate such

assessments for future trials.41, 42 Another limitation in this review was insufficient reporting. Investigators of future trials are therefore well advised to adhere to the Consolidated Standards for Reporting of Trials in order to improve the quality of trial reports.43 These potential limitations and concerns may lower our confidence in the estimates of intervention effect. However, in our meta-analysis for SVR there is no apparent heterogeneity (I2 = 0%), and the direction of the treatment effect is the same across all included trials. Further research is unlikely to change our confidence in the estimate of the effect. It is a common misconception that large RCTs are generally more reliable than meta-analyses. The reason this misconception has prevailed is due to a number of highly

cited papers that compared high-quality large trials with collections of low-quality small trials (an unfair comparison). In empirical studies where high-quality large trials are compared with a collection of high-quality small trials, the results from the two are typically nondiscrepant. In the case of the IDEAL trial,3 the results still show an effect—albeit small—in favor of peginterferon alpha-2a. There are many examples of large trials that underestimate the treatment effect simply by chance. Current evidence suggests that peginterferon alpha-2a is significantly superior to beta-catenin mutation peginterferon alfa-2b regarding benefits (SVR, which is clearance of the virus from the blood). However, there is insufficient evidence to detect any differences regarding harms (mortality and adverse events). Future trials must further the correlation between achieving SVR and clinically relevant outcomes such as risk of cirrhosis, hepatocellular carcinoma, and mortality. Glycogen branching enzyme We thank the patients and investigators who participated

in the included trials, with special thanks to the investigators who responded to our inquiries. We also thank our colleagues Dimitrinka Nikolova and Sarah Louise Klingenberg. “
“Dorrell C, Erker L, Schug J, Kopp JL, Canaday PS, Fox AJ, et al. Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes Dev 2011;25:1193-1203. (Reprinted with permission.) The molecular identification of adult hepatic stem/progenitor cells has been hampered by the lack of truly specific markers. To isolate putative adult liver progenitor cells, we used cell surface-marking antibodies, including MIC1-1C3, to isolate subpopulations of liver cells from normal adult mice or those undergoing an oval cell response and tested their capacity to form bilineage colonies in vitro.

Hopefully, the initiation

Hopefully, the initiation selleck kinase inhibitor of the World Health Organization International Clinical Trials Registry Platform will facilitate such

assessments for future trials.41, 42 Another limitation in this review was insufficient reporting. Investigators of future trials are therefore well advised to adhere to the Consolidated Standards for Reporting of Trials in order to improve the quality of trial reports.43 These potential limitations and concerns may lower our confidence in the estimates of intervention effect. However, in our meta-analysis for SVR there is no apparent heterogeneity (I2 = 0%), and the direction of the treatment effect is the same across all included trials. Further research is unlikely to change our confidence in the estimate of the effect. It is a common misconception that large RCTs are generally more reliable than meta-analyses. The reason this misconception has prevailed is due to a number of highly

cited papers that compared high-quality large trials with collections of low-quality small trials (an unfair comparison). In empirical studies where high-quality large trials are compared with a collection of high-quality small trials, the results from the two are typically nondiscrepant. In the case of the IDEAL trial,3 the results still show an effect—albeit small—in favor of peginterferon alpha-2a. There are many examples of large trials that underestimate the treatment effect simply by chance. Current evidence suggests that peginterferon alpha-2a is significantly superior to Sotrastaurin peginterferon alfa-2b regarding benefits (SVR, which is clearance of the virus from the blood). However, there is insufficient evidence to detect any differences regarding harms (mortality and adverse events). Future trials must further the correlation between achieving SVR and clinically relevant outcomes such as risk of cirrhosis, hepatocellular carcinoma, and mortality. Prostatic acid phosphatase We thank the patients and investigators who participated

in the included trials, with special thanks to the investigators who responded to our inquiries. We also thank our colleagues Dimitrinka Nikolova and Sarah Louise Klingenberg. “
“Dorrell C, Erker L, Schug J, Kopp JL, Canaday PS, Fox AJ, et al. Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes Dev 2011;25:1193-1203. (Reprinted with permission.) The molecular identification of adult hepatic stem/progenitor cells has been hampered by the lack of truly specific markers. To isolate putative adult liver progenitor cells, we used cell surface-marking antibodies, including MIC1-1C3, to isolate subpopulations of liver cells from normal adult mice or those undergoing an oval cell response and tested their capacity to form bilineage colonies in vitro.

2% (F2, p=007); suggesting NK killing & anti fibrotic responses

2% (F2, p=0.07); suggesting NK killing & anti fibrotic responses in early stages. CD56dim CD107a was unchanged (19.6±2.1%) within advanced fibrosis (F3-F4 cases, p=ns); suggesting NK impairment in advanced disease. Compared

to 68.6±8% in healthy volunteers, insulin receptors expressions found reduced to 48.4±3.3 – 52.5±2.5% in all stages of NAFLD CD56dim population (P<0.05); suggesting NK cell insulin resistance mediates impairment in advanced NVP-AUY922 in vitro stages. NAFLD CD56dim population showed lower F-Ac-tin (from 34±7.1 in healthy donors to 15.4±1.9% in NAFLD cases, p=0.03) and mTOR expressions (from 96.9±2.3 to 24.9±6.4%, respectively, p=0.001); suggesting F-Actin and mTOR to mediate NK killing. In vitro NK cultures with insulin incubations significantly unleashed the CD107a to increase NK killing in low fibrosis. This response attenuated in the insulin resistance NK cells of advanced

disease. Insulin activation of NK cells blocked by Rapamune administration; Ulixertinib solubility dmso suggesting insulin to increase NK activity via IR receptor in an mTOR mediated pathway that is prevented in insulin resistance. Conclusions: NAFLD NK cells exert insulin resistance and impairment, mainly the CD56Dim cytolytic population. Insulin resistance a result of metabolic modifications blocks insulin induced NK activity, via an mTOR dependent F-Actin scaffolding proteins. This pathway is indicating a new cellular pathway through which NK cells contribute to the NAFLD progression. Disclosures: The following people have nothing to disclose: Thymidine kinase Johnny Amer, Sarit Doron, Ahmad Salhab, Rifaat Safadi C-Myc has pleiotropic effects on proliferation, cell cycle control, differentiation and metabolism. Previous studies have specifically shown that c-Myc expression promotes transition from G0/G1 to S phase by regulating several networks of genes in mice after 2/3partial hepatectomy(PH). Contrary however, several studies have also shown that c-Myc appears to be dispensable for normal liver growth during the postnatal period, restoration of liver mass following PH and recovery from fasting. Aim of

this study was to clarify the role of c-Myc in liver regeneration during chronic liver injury. Mdr2-/— mice were crossed with c-Mycfl/flAlbCre+-mice to specifically delete c-Myc in hepatocytes. To induce liver regeneration, PH and hepatocyte transplantations were performed. Livers were harvested for immunhistochemical and biochemical analysis at several time points following PH. Hepatocyte transplantations were performed with immune-suppressed Fah-/—mice. Livers were harvested 8 weeks after transplantation. Mdr2-/-c-MycΔ/Δ mice developed significantly more severe liver injury compared to c-Myc WT littermates. Despite increased liver injury, baseline liver regeneration was however similar between Mdr2-/-c-MycA/A and Mdr2-/-c-Mycfl/fl mice. Following PH, liver regeneration proceeds in Mdr2-/-c-Mycfl/ fl mice similar to WT mice.

4%, respectively) (P > 005) The serum PG I, PG II and PGR in th

4%, respectively) (P > 0.05). The serum PG I, PG II and PGR in the same disease patients was no statistical difference between anti-Hp IgG positive and anti-Hp IgG negative (P > 0.05). Conclusion: 1) The PGR is a downward trend in the healthy controls, superficial gastritis group, peptic ulcer group, atrophic gastritis group, dysplasia group and gastric cancer group. 2) The changes in serum PG were significantly related with gastric cancer and gastric precancerous lesions. When PG I ≤ 73.14 ng/ml

or PGR ≤ 4.79, that MI-503 research buy has better specificity and sensitivity to gastric carcinoma, and has important clinical value to the diagnosis for the gastric cancer and precancerous lesions. 3) The HP infection has little effects on the changes of serum pepsinogen levels in patients with gastric cancer, gastric precancerous lesions, and its definite mechanism remains to be further studied. Key Word(s): 1. Gastric cancer; 2. Precancerous lesion; 3. Pepsinogen; 4. H. pylori; Presenting Author: YANG

XIAOJUN Additional Authors: ZHAO XIAOYAN Corresponding Author: ZHAO XIAOYAN Affiliations: Department of Gastroenterology, XinQiao Hospital Objective: Conventional catheter pH monitoring for diagnosing gastroesophageal reflux disease (GERD) produces discomfort, inconvenience and interferes with daily activity. This study assessed the feasibility STA-9090 manufacturer and safety of using a newly developed wireless JSPH-1 pH capsule system to monitor pH in patients with GERD. Methods: Ninety-one patients with symptoms suggestive of GERD entered the study. All patients underwent esophageal pH monitoring using the JSPH-1 pH capsule. Forty-five patients used conventional catheter pH measurement (MMS) as self-paired controls. The electrodes were positioned at the same level under chest X-ray. The pH data were recorded and capsule detachment was assessed by chest X-ray. Results: The capsule was successfully this website attached, and evaluable 24 h pH recordings were obtained in all patients. There were no significant differences of 24 h esophageal acid exposure

recorded by the JSPH-1 pH capsule and MMS catheter in terms of total number of reflux episodes, the number of episodes longer than 5 min, the longest reflux time and percentage of total time with pH < 4.0. Esophageal acid exposure over 24 h measured by the two devices showed a significant correlation (r2 = 0.996, P < 0.001). Concordance of the diagnosis of GERD was 100% (κ = 1.000). Capsule detachment occurred spontaneously in 89 patients; two capsules required endoscopic removal due to chest pain. No severe adverse events were reported. The capsule system was associated with less interference with daily activity and diet. Conclusion: The JSPH-1 pH capsule provided a feasible and safe method for monitoring reflux in patients with GERD. Key Word(s): 1. JSPH-1 pH capsule; 2. GERD; Presenting Author: CHENWEI CHANG Additional Authors: YE NI, QIANYI TING, ZHANGGUANG BO Corresponding Author: CHENWEI CHANG Affiliations: Department of Gastroenterology.

4%, respectively) (P > 005) The serum PG I, PG II and PGR in th

4%, respectively) (P > 0.05). The serum PG I, PG II and PGR in the same disease patients was no statistical difference between anti-Hp IgG positive and anti-Hp IgG negative (P > 0.05). Conclusion: 1) The PGR is a downward trend in the healthy controls, superficial gastritis group, peptic ulcer group, atrophic gastritis group, dysplasia group and gastric cancer group. 2) The changes in serum PG were significantly related with gastric cancer and gastric precancerous lesions. When PG I ≤ 73.14 ng/ml

or PGR ≤ 4.79, that ABT-199 datasheet has better specificity and sensitivity to gastric carcinoma, and has important clinical value to the diagnosis for the gastric cancer and precancerous lesions. 3) The HP infection has little effects on the changes of serum pepsinogen levels in patients with gastric cancer, gastric precancerous lesions, and its definite mechanism remains to be further studied. Key Word(s): 1. Gastric cancer; 2. Precancerous lesion; 3. Pepsinogen; 4. H. pylori; Presenting Author: YANG

XIAOJUN Additional Authors: ZHAO XIAOYAN Corresponding Author: ZHAO XIAOYAN Affiliations: Department of Gastroenterology, XinQiao Hospital Objective: Conventional catheter pH monitoring for diagnosing gastroesophageal reflux disease (GERD) produces discomfort, inconvenience and interferes with daily activity. This study assessed the feasibility Hedgehog antagonist and safety of using a newly developed wireless JSPH-1 pH capsule system to monitor pH in patients with GERD. Methods: Ninety-one patients with symptoms suggestive of GERD entered the study. All patients underwent esophageal pH monitoring using the JSPH-1 pH capsule. Forty-five patients used conventional catheter pH measurement (MMS) as self-paired controls. The electrodes were positioned at the same level under chest X-ray. The pH data were recorded and capsule detachment was assessed by chest X-ray. Results: The capsule was successfully O-methylated flavonoid attached, and evaluable 24 h pH recordings were obtained in all patients. There were no significant differences of 24 h esophageal acid exposure

recorded by the JSPH-1 pH capsule and MMS catheter in terms of total number of reflux episodes, the number of episodes longer than 5 min, the longest reflux time and percentage of total time with pH < 4.0. Esophageal acid exposure over 24 h measured by the two devices showed a significant correlation (r2 = 0.996, P < 0.001). Concordance of the diagnosis of GERD was 100% (κ = 1.000). Capsule detachment occurred spontaneously in 89 patients; two capsules required endoscopic removal due to chest pain. No severe adverse events were reported. The capsule system was associated with less interference with daily activity and diet. Conclusion: The JSPH-1 pH capsule provided a feasible and safe method for monitoring reflux in patients with GERD. Key Word(s): 1. JSPH-1 pH capsule; 2. GERD; Presenting Author: CHENWEI CHANG Additional Authors: YE NI, QIANYI TING, ZHANGGUANG BO Corresponding Author: CHENWEI CHANG Affiliations: Department of Gastroenterology.

Hepatoprotective effects of IL-22 were found in a primary Plasmod

Hepatoprotective effects of IL-22 were found in a primary Plasmodium chabaudi infection model,[13] but IL-22

did not show any protective effects against liver lesions Navitoclax datasheet infected by the parasite Toxoplasma gondii and Mycobacterium avium.[24] In addition, in a model of hepatitis B virus (HBV) replication in HBV transgenic mice, blocking IL-22 with a neutralizing antibody ameliorated liver damage by reducing chemokine expression on hepatocytes, and subsequently preventing hepatic recruitment of inflammatory cells, suggesting that IL-22 may contribute to the pathogenesis of HBV-mediated liver inflammation and injury.[25] The liver has great regenerative ability after injury induced by hepatotoxins, infections, or loss of tissues. Under most conditions, the liver can regain its original mass through the proliferation of mature healthy hepatocytes. However, when mature hepatocytes are unable to properly proliferate to restore damaged liver during severe or chronic liver injury, LPC-mediated liver repair

will be utilized to compensate liver functions.[26-31] The beneficial effects of IL-22 on mature hepatocyte survival and proliferation have been well documented.[10-20] Recent studies from our lab suggest that IL-22 also promotes LPC growth in patients with chronic this website viral hepatitis and in mice challenged by feeding a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet or a choline-deficient, ethionine-supplemented diet.[21] Increased IL-22 expression was observed in patients with chronic HBV or HCV infection.[19, 24, 32] IL-22 expression correlated with LPC proliferation in HBV patients, which implies that IL-22 may promote LPC growth in those patients.[21] IL-22TG mice with IL-22

overexpression in the liver were not associated with increased LPC number under a normal chow, but showed significant higher LPC proliferation rate and total LPC number compared with wild-type (WT) mice after being fed a DDC diet.[21] This suggests that IL-22 alone does not initiate LPC activation, but it can promote existing LPC proliferation in vivo in the DDC model. The LPCs that were isolated from the DDC-fed mice expressed Glycogen branching enzyme high levels of IL-22R1 and IL-10R2. This is not surprising because IL-22R1 is known to be expressed on epithelial cells, and LPCs are the progenitor cells for liver epithelial cells, including hepatocytes and biliary epithelial cells. In vitro treatment with IL-22 promotes proliferation of primary LPCs from the DDC-fed mice or proliferation of the LPC cell line, BMOL (bipotential mouse oval liver) cells,[21] suggesting that IL-22 directly stimulates LPC proliferation. It has previously been well documented that STAT3 activation mediates many functions of IL-22 in hepatocytes. Recently, we have provided several lines of evidence that suggest that STAT3 also plays an important role in IL-22-mediated stimulation of LPC proliferation.

0001) A

0001). A BAY 80-6946 mouse higher proportion of patients with HBsAg level >4.3 logIU/mL (p=0.009) and HBV DNA level ≤4.3 log IU/mL (p=0.0001) was observed in F0-1 patients. Presence of BCP variant was significantly associated with a more severe liver disease (p<0.0001). Conversely, PC variant proportion was higher in F0-1 patients. IL28B CC genotype was more frequent in patients with HBsAg level <3.3 log IU/mL (p=0.004). In mul-tivariate analysis, fibrosis stage was independently associated with age (p=0.0002), HBeAg

status (p=0.01), activity (p<0.0001) and BCP variant presence (p=0.008). The ROC analysis showed an AUC of 0.82 for the predictive model (age + HBeAg status + activity + HBeAg mutations) to identify F2-4 patients. Conclusion: Our study shows that patients with BCP variants were more at risk of cirrhosis. A strong correlation between age, activity grade, HBeAg status, HBV variants and fibrosis stage allows an accurate identification of subjects with moderate to severe liver disease who need to be treated. Our results suggest that detection of HBV variants is clinically relevant

for the assessment of the severity Wnt antagonist of HBV related liver disease. Disclosures: Olivier Lada – Grant/Research Support: Gilead Nathalie Boyer – Board Membership: MSD, JANSSEN; Speaking and Teaching: BMS Tarik Asselah – Consulting: BMS, Boehringer-Ingelheim, Roche, Merck-Schering Plough, Gilead, Janssen Patrick Marcellin – Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen-Tibotec, MSD, Boehringer, Pfizer, Abbott, Alios BioPharma; Grant/Research Support: Roche, Gilead, BMS, Novartis, Janssen-Tibotec, MSD, Alios BioPharma; Speaking and Teaching: Roche, Gilead, BMS, Vertex, Novartis, Janssen-Tibotec, Ribonucleotide reductase MSD, Abbott The following people have nothing to disclose: Martine Lapalus, Michelle

Mar-tinot-Peignoux, Ana Carolina Cardoso, Roberto J. Carvalho-Filho, Cédric Laoué-nan, Simon Gosset, Zhang Qian, Emilie Estrabaud, Feryel Mouri Aim: The study aimed to investigate HBV rtA181T mutation profile in clinical practice and its clinical implications. Methods: Serum samples from 1 8,41 9 patients collected from July 2007 to June 2012 in Beijing 302 Hospital were investigated. Around 92% patients experienced nucleos(t)ide analogs. The rtA181T mutation and HBV genotype were determined by direct sequence analysis. Viral replication capacity, drug susceptibility and HBsAg secretion were determined in HepG2 cells that had been transfected with replication-competent HBV vectors containing reverse-transcriptase/S genes. Results: rtA181T was detected from 750 patients. The incidence escalated in the past five years (1.97%, 2.47%, 3.84%, 5.21%, and 6.35%); rtA181T emerged either alone or with other drug-resistant mutations (37.3% alone, 48.6% with adefovir-resistant mutation rtA181V/N236T, 12.1% with lamivudine-resistant mutation rtM204V/rtM204I, and 2.0% with entecavir- or multidrug-resistant mutations, respectively). In patients harboring rtA181T, 96.

Key Word(s): 1 miR-155; 2 EMT; 3 ERK1

pathway; 4 HSC;

Key Word(s): 1. miR-155; 2. EMT; 3. ERK1

pathway; 4. HSC; Presenting Author: SHIRAN SHETTY Additional Authors: KRISHNAVENI JANARATHANAN, LEELAVENKATAKRISHNAN VENKATAKRISHNAN Corresponding Author: SHIRAN SHETTY Affiliations: PSGIMSR Objective: Bacterial infections are the common cause of morbidity and mortality in chronic liver disease patients. Infections in patients with liver disease have a different clinical presentation and early identification is important for good outcome. Increasing prevalence and antibiotic resistance are on the rise. we aimed CP-868596 chemical structure to evaluate the recent changes in microorganisms causing clinical/ sub-clinical infections in cirrhotic patients and their antibiotic resistance pattern. Methods: In this retrospective study, 150 patients of chronic liver disease admitted in department of gastroenterology PSG medical college hospital, Coimbatore india were

included in this study over one year. Institutional Ethics Committee approval was obtained regarding inclusion and exclusion criteria, prior to commencement of study. Results: Of the 150 patients, 58 (38.7%) were found to have culture positive infection. While the most common bacteria isolated from our study was E coli, we also noticed an increasing trend of Gram positive organisms like Staphylococcus. AZD8055 nmr Our study showed nearly 50% of organism being resistant to 3rd generation Cephalosporins and fluoroquinolones, unlike previous studies. Conclusion: Appropriate usage of antibiotics and strict adherence

of hospital antibiotic policy is required to prevent emergence of resistant organism. Key Word(s): 1. cirrhosis; 2. bacteria infection; 3. resistance; 4. Ecoli; Presenting Author: JUAN ZHAO Additional Authors: NAN TANG, KAIMING WU, WEIPING DAI, CHANGHONG YE, JIAN SHI, BEIFANG NING, XIN ZENG, YONG LIN Corresponding Author: XIN ZENG, YONG LIN Affiliations: Shanghai Changzheng Hospital, Second Military Medical University; Department of Gastroenterology, Shanghai Changzheng Hospital Objective: Activation of extracellular signal-regulated kinase 1 (ERK1) signaling pathway in hepatic stellate cell (HSC) and epithelial-mesenchymal transition (EMT) process in hepatocyte are considered as the important contributors to promoting accumulation of activated fibroblasts and exacerbating hepatic fibrosis. Enhancement of microRNA-21 (miR-21) expression has been Molecular motor confirmed in activated HSC and fibrotic liver. The aim of this study was to explore the mechanism of miR-21 participating in the simultaneous regulation of ERK1 pathway and EMT process in both of HSC and hepatocyte during hepatic fibrogenesis. Methods: miR-21 levels were determined in liver tissues or serum from fibrotic models or serum from patients. Luciferase reporter assay was performed to validate whether miR-21 could directly target sprouty2 (Spry2) and hepatocyte nuclear factor 4α (HNF4α) through 3′-untranslated region (3′-UTR) interactions respectively.

The remaining 461 patients (264 men, 197 women; age range 38–93 y

The remaining 461 patients (264 men, 197 women; age range 38–93 years; mean age 68.2 ± 8.7 years) were enrolled in this study. They consisted of 107 (23.2%) elderly subjects, aged PD0325901 in vivo 75 years or over, and 354 non-elderly subjects. According to the estimate released by the National Cancer Center, Japan, the number of liver cancer mortalities in Japanese persons aged over 75 years increased, whereas that of subjects under 75 years decreased between 2004 and 2008.16 Additionally, the incidence of liver cancer continually increased in Japanese persons over 75 years

until 2005, whereas the incidence in persons under 75 years reached its peak in 2003.17 Therefore, we divided subjects into two groups (those <75 years and those ≥75 years) to analyze and discuss the strategy of treatment for elderly HCC patients. The indication for RFA treatment was that HCC consisted of five or fewer nodules, with each nodule having a maximum diameter of 30 mm, or that HCC consisted of a single tumor, regardless of size, and that hepatic function was not Child–Pugh grade C. PF-02341066 mouse Radiofrequency ablation treatment was applied to cases (n = 226) that were not considered

to be suitable for resection for the following reasons: (i) impairment of liver function, and (ii) an excessive number of tumors or cardiopulmonary dysfunction. In addition, we applied RFA in cases (n = 235) where patients chose ablation therapy

even though surgery was also feasible. Exclusion criteria for RFA were: (i) Inositol oxygenase total bilirubin concentration over 3 mg/dL; (ii) platelet count under 30 000/mm3; (iii) prothrombin activity under 50%; (iv) ascites that could not be controlled by nutritional therapy and diuretics; and (v) patients with portal vein tumor thrombosis or extrahepatic metastasis. When four or more nodules were detected or the largest nodule was over 3 cm, RFA was preceded by transcatheter arterial chemoembolization (TACE) using epirubicin and gelatin sponge particles. Using combined examinations from ultrasonography and dynamic computed tomography (CT) scans or dynamic magnetic resonance imaging (MRI) or CT during angiography, diagnosis of HCC was confirmed in cases where the contrast pattern of the nodule in CT or MRI was hypervascular in the arterial phase and hypovascular in the portal phase. If the nodules were not consistent with typical contrast patterns for HCC, a needle biopsy of the tumor was taken for pathological diagnosis. The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) 6th edition staging system for HCC was used for Tumor–Node–Metastasis (TNM) classification.18 The following three RF systems were used. From January 2000 to March 2000, 25 patients underwent RFA treatment using an RF 2000 generator system (Radio Therapeutics, Mountain View, CA, USA).

CHB subjects with HBV DNA >2 x 1 03 IU/mL and ALT ≦10 x ULN recei

CHB subjects with HBV DNA >2 x 1 03 IU/mL and ALT ≦10 x ULN received treatment with TAF at doses of 8, 25, 40, and 120 mg, or TDF 300 mg for 28 days

with 4 weeks off-treatment follow-up. Intensive pharmacokinetics (PK) were performed on Day 1. Results: 51 subjects were enrolled and completed 28 days of dosing. Groups were well matched at baseline (table) and subjects were mostly male and either Asian or Black; 53% were HBeAg-negative. No subject experienced a serious adverse event (SAE), grade 3/4 AE, or discontinued for AE. No subject experienced a renal event (>0.5 mg/dL increase in creatinine from baseline, phosphorus <2 mg/dL, or CrCL <50 mL/min). The kinetics of reduction in serum HBV DNA were similar across all TAF dose groups and comparable to TDF. PK analysis suggested mean reductions in TFV exposures (AUCinf) of 97%, 93%, 81 %, ICG-001 concentration and 32% at TAF doses of 8, 25, 40, and 120 mg, respectively, relative to the mean TFV exposure with TDF. Conclusions: Over 28 days, TAF was safe and well tolerated. Declines in HBV DNA with TAF did not differ by dose and were similar to TDF. Additionally, TAF may have less impact on renal function (CrCL) compared to TDF. Further clinical trials with TAF are warranted in CHB patients.   TAF 8 mg (N=10) TAF 25 mg (N=10) TAF 40 ng (N=ll) TAF 120 mg (N=10) TDF 300 mg (N=10) Results are median (IQR) unless otherwise stated. Disclosures:

Kosh Agarwal – Advisory Committees or Review Panels: Gilead, Novartis, Abbott; Grant/Research Support: Roche, MSD; Speaking and Teaching: BMS, Astellas, Janssen Scott K. Fung – Advisory Committees or Review Panels:

BMS, Vertex, Gilead Sciences; Dabrafenib Grant/Research Support: Gilead Sciences, Hoffman La Roche, Merck; Speaking and Teaching: Gilead Sciences, Hoffman La Roche, Merck, BMS Tuan T. Nguyen – Grant/Research Support: Bristol Myers Squibb, Gilead Sciences, Idenix Pharmaceuticals Incorporation, Globeimmune Pharmaceuticals, Vertex Pharmaceuticals John F. Flaherty – Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Eileen Lawson – Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead Sciences, Inc. Mani Subramanian – Employment: Gilead Sciences John G. McHutchison – Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Edward J. Gane – Advisory Committees or Review Panels: Roche, AbbVie, Novartis, Tibotec, Gilead Sciences, Janssen Chlormezanone Cilag, Vertex, Achillion; Speaking and Teaching: Novartis, Gilead Sciences, Roche Graham R. Foster – Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Chughai, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS; Board Membership: Boehringer Ingelheim; Grant/Research Support: Chughai, Roche, Chughai; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen The following people have nothing to disclose: Wendy Cheng, Eric Sicard, Stephen D.