013). Similarly, among participants with rs12979860 genotyping (n = 202), clearance was higher in those with the favorable IL28B CC genotype (20%) as compared to those with unfavorable IL28B CT/TT genotypes (8%; P = 0.016). There was an association with HCV RNA level at acute HCV detection and clearance. Individuals with HCV RNA levels <4 log IU/mL were more likely to achieve spontaneous clearance (24%) as compared to those with HCV Erismodegib RNA of 4-6 log IU/mL (9%; P = 0.012) and those with HCV RNA >6 log IU/mL (7%, P = 0.060). There was no difference in HCV RNA level by IL28B genotype. Although

patients with unfavorable IL28B genotypes tended to have higher IP-10 levels at acute HCV detection, there was no association between IL28B genotype and IP-10 above 380 pg/mL (47% with IP-10 >380 pg/mL were TT at rs8099917). The combination of IL28B genotype and plasma IP-10 levels demonstrated spontaneous clearance as follows: low IP-10 (<380 pg/mL) and favorable rs8099917 TT IL28B genotype (22%), high IP-10 and favorable rs8099917 TT IL28B genotype (0%), low IP-10 and unfavorable rs8099917 GT/GG IL28B genotype (9%), and high IP-10 and unfavorable Gefitinib supplier rs8099917 GT/GG IL28B genotype (0%, Supporting Fig. 3). In adjusted logistic regression analyses, IL28B genotype (rs8099917TT

versus GG/GT genotype, AOR 4.22, 95% CI: 1.34, 13.28; P = 0.014) was associated with higher odds of spontaneous clearance, while higher HCV RNA level Dynein was independently associated with lower odds of spontaneous clearance (<4 versus 4-6 log IU/mL, AOR 0.28, 95% CI: 0.11, 0.75 and <4 versus >6 log IU/mL, AOR 0.19, 95% CI: 0.04, 0.93). Given that plasma IP-10 levels ≥380 pg/mL were 100% predictive of not achieving spontaneous clearance, plasma IP-10 levels could not be incorporated into adjusted models of factors associated with spontaneous clearance. As a continuous variable, IP-10 levels at acute HCV detection were not associated with spontaneous

clearance (OR 0.54, 95% CI: 0.16, 1.87). Identification of factors associated with spontaneous clearance after acute HCV infection has potentially important clinical and pathophysiological significance. This study of a large sample with acute HCV showed that IP-10 levels at detection of acute infection were associated with spontaneous clearance and no patients with very high IP-10 levels (≥380 pg/mL) achieved clearance. IP-10 levels correlated with HCV RNA levels at acute HCV detection and higher HCV RNA levels (≥4 log IU/mL) predicted subsequent HCV persistence, independent of IL28B genotype. Based on these data, early therapy may be considered in individuals with high IP-10 (≥380 pg/mL) and higher HCV RNA levels, given the low likelihood of spontaneous clearance, regardless of IL28B genotype. Patients with spontaneous clearance had lower mean, but similar median, IP-10 levels at the time of acute HCV detection than those with persistence.

Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method. Results:  Fourteen-day therapy led to a significant increase of H. pylori eradication success when compared to 7-day therapy in the intention-to-treat analysis (93.7 vs 80.0%; p = .01), and the per-protocol analysis (97.4 vs 82.0%;

p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin selleck kinase inhibitor and amoxicillin were 42.1, 18.0 and 0%. Fourteen-day therapy was significantly more effective in patients with clarithromycin-resistant strains. Incidences of adverse events were comparable. Conclusions:  Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen-day triple therapy-based, bismuth-containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen. “
“Background: 

Sequential regimens have been recently reported to be superior to the standard triple therapies in Helicobacter pylori eradication, but Palbociclib solubility dmso most of these studies were performed in Europe and data from developing countries are lacking. So we designed a study to compare a sequential regimen with a bismuth-based quadruple therapy that contains a short course of furazolidone, in Iran. Methods:  Two hundred and ninety-six patients with duodenal ulcer and naïve H. pylori infection were randomized into two groups: 148 patients received (PAB-F) pantoprazole (40 mg-bid), amoxicillin (1 g-bid), and bismuth subcitrate (240 mg-bid) for 2 weeks and furazolidone (200 mg-bid) just during the first week. And 148 patients received (PA-CT) pantoprazole (40 mg-bid) Baricitinib for 10 days, amoxicillin (1 g-bid) for the first 5 days, and clarithromycin (500 mg-bid) plus tinidazole (500 mg-bid) just during the second 5 days. C14-urea breath test was performed 8 weeks after the treatment. Results:  Two hundred and sixty-one patients completed the study (137 patients in the PA-CT and 124 in the PAB-F group). The results were not statistically different between the two

groups in the eradication rates and the severity of side effects. The intention to treat eradication rate was 80.4% in the PAB-F group and 83.7% in the PA-CT group. Per-protocol eradication rates were 88.7% and 89.1%, respectively. Conclusion:  Because the two regimens showed acceptable and similar abilities in H. pylori eradication and because of much higher cost of clarithromycin in Iran, the furazolidone containing regimen seems to be superior. Further modifications of sequential therapies are needed to make them ideal regimens in developing countries. “
“Background and Aim:  Eradication rate for Helicobacter pylori infection with standard triple therapy has globally declined including in Thailand, and new regimens are required that provide reliable high eradication rates.

(HEPATOLOGY 2012;56:1622–1630) Boceprevir (800 mg three times a day), in combination with pegylated interferon-α (PEG-IFNα) and ribavirin, was approved in the United States and Europe for the treatment of genotype 1 chronic hepatitis C infection in adult patients with compensated liver disease. As a structurally novel ketoamide serine protease inhibitor of the hepatitis C virus (HCV) nonstructural 3 (NS3/4A) active site, boceprevir has been shown to significantly increase rates XL765 of sustained virologic response (SVR) when added to PEG-IFNα plus ribavirin as compared with treatment with PEG-IFNα plus ribavirin alone.1, 2 In treatment-naive

patients, SVR rates increased from 38% among patients treated with PEG-IFNα plus ribavirin to 63%-66% in those receiving boceprevir plus PEG-IFNα and ribavirin.2 Similarly, in treatment-experienced

patients, SVR rates were 21% with PEG-IFNα plus ribavirin and 59%-66% in those receiving boceprevir plus PEG-IFNα and ribavirin.1 Boceprevir (800 mg Sunitinib three times a day) in combination with PEG-IFNα and ribavirin, was approved for the treatment of genotype 1 chronic hepatitis C infection in adult patients with compensated liver disease in the United States and Europe in 2011. Metabolism of boceprevir occurs by aldo-ketoreductase to form inactive keto-reduced metabolites and by cytochrome P450 3A4 and 3A5 (CYP3A4/5).3 Boceprevir is also a substrate for the efflux pump P-glycoprotein (P-gp) and is an inhibitor

of OATP1B1.4 Hepatitis C–related liver cirrhosis is a frequent cause of liver transplantation, and because recurrent viremia is common among patients who are viremic at the time of transplantation, treatment http://www.selleck.co.jp/products/CHIR-99021.html of HCV infection is frequently required after transplantation.5 Cyclosporine and tacrolimus are calcineurin inhibitors widely used to prevent solid organ transplant rejection. Both agents are substrates for CYP3A6, 7 and P-gp.8 Cyclosporine is also an inhibitor of several other transporter proteins, including OATP1B1 and OATP1B3.9 Both agents have a narrow therapeutic index, with therapeutic monitoring being required to avoid either underexposure, which can result in organ rejection, or excess exposure, which may cause nephrotoxicity, neurotoxicity, hypertension, or gastrointestinal toxicity. Boceprevir is a strong inhibitor of CYP3A4/5 and would be anticipated to increase exposure to cyclosporine and tacrolimus upon coadministration, as was previously observed for another recently approved HCV NS3/4A protease inhibitor (telaprevir, Incivek, Vertex Pharmaceuticals, Inc.).10 In this study, the pharmacokinetic (PK) interactions between boceprevir and tacrolimus/cyclosporine were separately evaluated.

Results indicated that stable overexpression of miR-216a/217 in the PLC/PRF/5-miR-216a/217 cells significantly promoted tumor growth in an orthotopic xenograft tumor model (Fig. 3E). More significantly, when lung tissues of mice were harvested at the end point of the experiments, all of the mice inoculated with PLC/PRF/5-miR-216a/217 cells gave good bioluminescent signals, Peptide 17 indicating the presence of lung metastases (Fig. 3F). In contrast, no lung bioluminescent signals

were detected in mice inoculated with PLC/PRF/5-P-miR-control cells (Fig. 3F). These data indicate that overexpression of miR-216a/217 increases stem-like properties and promotes tumor growth and metastases of epithelial HCC cells. To elucidate the molecular mechanisms by which the miR-216a/217 cluster induces EMT in HCC, we employed several computational algorithms to identify the potential functional targets for the miR-216a/217 cluster. Using miRecords, an integrated resource for microRNA-target interactions,[16]

a panel of molecules were predicted to be potential targets of the miR-216a/217 cluster with six miRNA target prediction programs (Supporting Table 2). Previously, we established an expression database for HCC using Obeticholic Acid cost Affymetrix Human Genome U133 plus 2.0 Arrays (Affymetrix).[9, 11] Expression of the predicted potential targets identified for the miR-216a/217 cluster was analyzed in our HCC expression database. It was identified that SMAD7 and Janus kinase 2 (JAK2) were significantly down-regulated in HCC, compared to adjacent histologically normal liver tissues (Supporting Fig. 5A,C). In comparison, expression of SMAD7, but not JAK2, in PLC/PRF/5-miR-216a/217 cells was significantly reduced (Fig. 4A). Previous reports demonstrated that PTEN is also a target of miR-216a/217.[17] PTEN was also significantly down-regulated in HCC, compared to adjacent histologically normal, liver tissue in our expression database for HCC (Supporting Ponatinib price Fig. 5B).

This prompted us to study the expression of PTEN in PLC/PRF/5-miR-216a/217 cells, revealing a significant down-regulation (Fig. 4A). The increased expression of SMAD7 and PTEN was also observed in mesenchymal phenotype HLE cells transfected with antagomir-miR-216a/217 (Supporting Fig. 3C). To further demonstrate that SMAD7 and PTEN are directly targeted by miR-216a/217 in HCC cells, we investigated whether the miR-216a/217 cluster directly interacted with the 3′-UTR of SMAD7 and PTEN mRNA by a dual-luciferase reporter assay. The predicted 3′-UTR sequence of SMAD7 and PTEN that interacted with miR-216a/217, together with a corresponding mutated sequence within the predicted target sites, were synthesized and inserted into the XbaI and FseI sites of the pGL3 control vector (Promega) (Supporting Fig. 6A-D). These constructs were referred to as pGL3-SMAD7-3′UTR-wt and pGL3-SMAD7-3′UTR-mut, pGL3-PTEN-3′UTR-wt, and pGL3-PTEN-3′UTR-mut.

Forty-six of 75 patients (61%) receiving HBsAg/HBcAg vaccine reduced the HBV DNA below 250 copies/ml Alpelisib cell line (unde-tectable HBV DNA) at EOT and a similar proportion remain below 250 copies/mL at the end of 24 weeks of treatment-free follow up. Fifty-one of 76 patients (67%) receiving Peg-IFN reduced the HBV DNA level below 250 copies/mL at EOT, however, only 39% remain under the same level at 24 weeks after EOT during treatment-free follow up. ALT increases were not clinically symptomatic in patients receiving HBsAg/HBcAg vaccine and a generalized normalization of ALT values in the majority

of patients at the EOT and 24 weeks of treatment-free follow up was recorded. Conclusions: A therapeutic vaccine therapy containing HBsAg/HBcAg represents a safe and efficacious therapeutic approach for CHB. This study inspired optimism that ongoing protocols of immune therapy against CHB may be improved by altering nature of antigens and route of administration. Disclosures: The following people have nothing to disclose: Sheikh Mohammad Fazle Akbar, Mamun A. Mahtab, Salimur Rahman, Julio Cesar Aguilar, Yoichi Hiasa, Shunji Mishiro Background: It is yet to be firmly established whether host IL28B genotype influences the response to peginterferon alfa-2a (40KD) (PegIFN) in patients with chronic hepatitis B (CHB). Associations between markers of host IL28B genotype (rs8099917,

rs12980275, rs12979860) and response to PegIFN were assessed using data from three large randomized studies. Methods: Patients with CHB (N=642) who had received 48 weeks’ https://www.selleckchem.com/products/ly2157299.html treatment with PegIFN 1 80 μg/week (with/without lamivudine) in three randomized international clinical Selleckchem Ponatinib studies were included. Treatment responses were determined 24 weeks after end of treatment and were defined as HBeAg seroconversion in HBeAg-positive patients and as HBV DNA <2000 IU/mL in HBeAg-negative patients. Three single nucleotide polymorphisms (SNPs) in

the IL28B region were investigated (rs8099917, rs12980275, rs12979860) using stored serum. Results: The study population included a total of 419 HBeAg-positive patients (92% Oriental, 63% HBV genotype C, 29% genotype B), of whom 151 (36.0%) had a response, and 223 HBeAg-negative patients (83% Oriental, 51% HBV genotype C, 29% genotype B), of whom 108 (48.4%) had a response. The distribution of IL28B genotypes at the three SNPs in HBeAg-positive and HBeAg-negative patients was as follows: 1) rs8099917TT, 87% and 87%, respectively; 2) rs1 2980275 AA, 82% and 83%, respectively; 3) rs12979860 CC, 80% and 79%, respectively. Associations between treatment response and the number of copies of the rare allele were explored with additive models. In HBeAg-positive patients there were no associations between IL28B genotypes and response to PegIFN (p=0.393-0.

Type 1 RS: Starch granules surrounded by indigestible plant matrix Type 2 RS: Found in natural form as high amylose content starch in maize, rice etc. Type 3 RS: Crystallized starches made by unique cooking and cooling processes Type 4 RS: Starch chemically modified by esterification, crosslinking, or transglycosylation Celluloses Hemicelluloses Gums Pectins Xylans Mannans Glucans Mucilages Lactose Fructose Sorbitol Lactitol Mannitol Maltitol Xylitol Fructooligosaccharides Raffinose Stachyose Inulin Polydextrose (used in food industry) In the study[12] Selleckchem PLX3397 cited in the previous section, in which three enterotypes

of the human gut microbiota were identified, metabolic pathway analysis led to some interesting conclusions. It suggested that the microbes of enterotype 1-derived energy mainly from the fermentation of carbohydrates and proteins, as they were enriched for genes representing saccharolytic enzymes, galactosidases, hexosaminidases, proteases, and enzymes in the glycolysis and pentose phosphate pathways. Enterotypes 2 and 3 were considered to derive energy significantly from mucin degradation, although the latter probably also had potential to utilize carbohydrates by fermentation by virtue of the presence VX-809 clinical trial of significant numbers of Bacteroides species. Enterotype 1 was enriched in enzymes involved in biosynthesis

of biotin, riboflavin, pantothenate, and ascorbate while enterotype 2 was enriched in enzymes involved in biosynthesis of thiamine and folate. Starch degradation enzymes increased with age, consistent with changing dietary patterns. Two marker modules that correlated strongly with host body mass index were identified to be ATPase complexes, reinforcing a link between gut microbiota and energy nutrition state in the host. Between 10% and 20% of ingested dietary carbohydrates are resistant to small intestinal digestion. These non-digestible dietary carbohydrates (NDC) include certain forms of starch that are resistant to amylase

digestion (resistant starch [RS]) as well as non-starch polysaccharides (NSPs) (Table 1).[24, 25] The NSP include substances such as pectin that are substrates for colonic FER bacterial metabolism, and substances such as cellulose that are not fermented by the colonic bacteria. Non-digestible dietary carbohydrates enter the colon where RS and fermentable NSP are fermented by colonic bacteria to SCFA, lactate, and gases such as CO2, H2, and methane (Fig. 1).[26, 27] RS, primarily from cereals but also from raw banana and potato, is a very important substrate for colonic fermentation.[24, 27, 28] While many commonly eaten foods have a significant content of type 2 RS (i.e. naturally present in the food source), the method of cooking and eating may enhance RS content of the food.

The peroxisome proliferator-activating receptor γ (PPARγ) is a member of the nuclear receptor superfamily of transcription factors. The role of PPARγ in the onset and treatment of cancer has been the focus of recent attention. PPARγ agonists inhibit the proliferative activity of neoplastic cells, suppress the growth of human tumor xenografts in nude mice,2, 3 and reduce the frequency of spontaneous and carcinogen-induced preneoplastic and neoplastic lesions in animals,2-5 which is indicative of the tumor suppressor effects of PPARγ.2 These observations have prompted phase II

clinical trials using PPARγ agonists as novel therapy for patients with liposarcoma, colon, breast, and prostate cancer.5, 6 Our group and others have previously demonstrated the antitumorigenic effects of PPARγ agonists Protein Tyrosine Kinase inhibitor in several liver cancer cell lines.7, 8 PPARγ agonist stimulation induced cell cycle arrest and apoptosis and inhibited

the growth of liver cancer cells.9-12 Thus, these findings support the hypothesis that PPARγ may act as a potent tumor suppressor in hepatocarcinogenesis. Of note, the antitumor effects of PPARγ agonists may be mediated via PPARγ-dependent and PPARγ-independent pathways,2, 13 but the role of PPARγ find more itself in hepatocarcinogenesis is still unclear. To elucidate the role of PPARγ in its therapeutic efficacy against HCC, diethylnitrosamine (DEN) was used to induce primary liver cancer in PPARγ wild-type (PPARγ+/+) and PPARγ heterozygous-deficient (PPARγ+/−) mice, followed by treatment with the PPARγ agonist rosiglitazone. We also examined the functional significance of endogenous PPARγ overexpression in human HCC cells using an adenovirus-PPARγ construct. ACOX, acyl-coenzymeA oxidases; Ad-PPARγ, adenovirus-expressing PPARγ; APAF, apoptotic protease activating factor; cDNA, complementary DNA; ChIP, chromatin immunoprecipitation; DEN, diethylnitrosamine; FACS,

fluorescence-activated cell sorting; Fn, fibronectin; GDF15, growth Vildagliptin differentiation factor 15; HCC, hepatocellular carcinoma; MOI, multiplicity of infection; PARP, nuclear enzyme poly(ADP-ribose) polymerase; PCNA, proliferating cell nuclear antigen; PCR, polymerase chain reaction; PI, propidium iodide; PPARγ, peroxisome proliferator-activated receptor gamma; PTEN, phosphatase and tensin homolog; TBXA2R, thromboxane A2 receptor; TNF, tumor necrosis factor; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; WT, wild-type. All homozygous PPARγ knockout animals were embryonically lethal due to placental dysfunction. We therefore used PPARγ heterozygous-deficient mice (PPARγ+/−) in this study. PPARγ-deficient (PPARγ+/−) mice were kindly supplied by Professor Frank J. Gonzalez (Center for Cancer Research, National Cancer Institute, Bethesda, MD). The generation of the transgenic mice was described previously.

huxleyi was decreased by 1.6-fold, whereas cellular volume Olaparib concentration was increased by 1.9-fold. Se limitation also decreased chl a (2.5-fold), maximum relative electron transport rate (1.9-fold), and saturating light intensity (2.8-fold), suggesting that Se plays a role in photosynthesis or

high-light acclimation. Pigment analysis for Antarctic taxa provided an interesting counterpoint to the physiology of E. huxleyi. For all Se-dependent Antarctic diatoms, Se limitation decreased growth rate and chl a content, whereas cellular volume was not affected. Pigment analysis revealed that other pigments were affected under Se deficiency. Photoprotective pigments increased by 1.4-fold, while diadinoxanthin:diatoxanthin Quizartinib molecular weight ratios decreased by 1.5- to 4.9-fold under Se limitation, supporting a role for Se in photoprotection. Our results demonstrate an Se growth requirement for polar diatoms and indicate that Se could play a role in the biogeochemical cycles of other nutrients, such as silicic acid in the Southern Ocean. Se measurements made during the austral summer in the Southern Ocean and Se biological requirement were used to discuss possible Se limitation in phytoplankton from contrasting oceanographic regions. “
“Mitochondrial DNA (mtDNA) of the isogamous brown alga Scytosiphon lomentaria (Lyngb.) Link is inherited maternally. We used molecular biological

and morphological analyses to investigate the fate of male mitochondria. Ultrastructural observations showed that the number of 25 mitochondria in a zygote coincided with

the number of mitochondria derived from male and female gametes. This number remained almost constant during the first cell division. Strain-specific PCR in single germlings suggested that mtDNA derived from the female gamete remained in the germling during development, while the male mtDNA gradually and selectively disappeared after the four-cell stage. One week after fertilization, male selleckchem mtDNA had disappeared in sporophytic cells. Using bisulfite DNA modification and methylation mapping assays, we found that the degree of methylation on three analyzed sites of mtDNA was not different between male and female gametes, suggesting that maternal inheritance of mtDNA is not defined by its methylation. This study indicates that the mechanism of selective elimination of male mtDNA is present in each cell of a four-celled sporophyte and that it does not depend on different degrees of DNA methylation between male and female mtDNA. “
“We investigated the relationship between daily growth rates and diel variation of carbon (C) metabolism and C to nitrogen (N) ratio under P- and N-limitation in the green algae Chlorella autotrophica. To do this, continuous cultures of C. autotrophica were maintained in a cyclostat culture system under 14:10 light:dark cycle over a series of P- and N-limited growth rates.

A significantly higher detection rate of H. bilis DNA (p = 0.009) was observed in patients with PBM [12/17 (70.6%)] when compared to controls [8/27 (29.6%)] suggesting that prolonged biliary colonization with H. bilis may contribute to the

development of biliary carcinoma in patients with PBM [3]. To determine the incidence of H. hepaticus in gallbladder disease associated with gallstones, Pradhan et al. conducted a study in which gallbladder tissue from 30 patients with cholelithiasis was studied by culture and histology. Of 30 samples, 23 (76.7%) showed growth of an oxidase, urease, and catalase-positive Gram-negative bacterium. On histologic analysis, 18/30 samples were positive for an H. hepaticus-like bacterium [4]. Further steps to confirm the identity of these isolates would have been advisable. Yoda et al. and Alon Selleckchem APO866 et al. [5,6] reported the isolation of Helicobacter cinaedi and H. canis from GSK-3 beta phosphorylation the blood of a febrile 58-year-old man on hemodialysis and a febrile 78-year-old man previously diagnosed with diffuse large B-cell lymphoma, respectively. Three further case reports described the detection of “Helicobacter heilmannii-like organisms” (HHLO) from gastric biopsies [7–9]. In the first of these, a spiral-shaped HHLO (SH6) was detected in a gastric biopsy from a 70-year-old

man. This was shown by 16S rDNA sequence analysis to be most similar (99.4%) to HHLO C4E, however the urease gene sequence had a lower similarity (81.7%), suggesting that SH6 was a novel species [7]. In a further study, Kivisto et al. detected a large spiral bacterium in gastric biopsies from a 45-year-old Finnish dyspeptic woman. Culture of antral and corpus biopsies resulted in the isolation of a large spiral, catalase, and urease positive, Gram-negative bacteria

resembling “H. heilmannii”. Based on sequencing of the 16S rRNA and ureAB genes as well as a Helicobacter bizzozeronii species-specific PCR, the bacterium was shown to be H. bizzozeronii [8]. Duquenoy et al. reported the histologic detection of a tightly spiral bacterium similar to “H. heilmannii” from a gastric biopsy Linifanib (ABT-869) of a 12-year-old boy with an erythematous mucosa. Endoscopy conducted on the boy’s two pet dogs found HHLOs to be present in their stomachs. 16S and 23S rDNA sequencing showed these to be identical to that in the boy, suggesting that he was infected by his dogs [9]. In a multicenter cross-sectional study, Laharie et al. examined intestinal biopsies from 73 CD patients with postoperative recurrence and 92 controls for the presence of EHH using culture, PCR, and genotyping of the Card15/NOD2 mutations, R702W, G908R, and 1007f. EHH DNA was detected in 24.7% of CD patients and 17.4% of controls. In all cases, H. pullorum or Helicobacter canadensis was identified. Multivariate analysis showed, younger age (OR = 0.89, p = 0.

Given that HCV is the main driver of

HCC in the U.S., better screening strategies and aggressive treatment see more of HCV patients with the newly developed highly effective interferon- and riba-virin-free regimens must be considered. Disclosures: Sammy Saab – Advisory Committees or Review Panels: BMS, Gilead, Merck, Genentech; Grant/Research Support: Merck, Gilead; Speaking and Teaching: BMS, Gilead, Merck, Genentech, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Salix, Johnson and Johnson, BMS, Gilead Brian P. Lam – Advisory Committees or Review Panels: BMS; Speaking and Teaching: Gilead; Stock Shareholder: Gilead The following people have nothing to disclose: Zobair Younossi, Maria Ste-panova, Sorafenib in vitro Kameron Tavakolian, Manirath Srishord, Chapy Venkatesan, James N. Cooper, Homan Wai, Linda Henry Background: Current HCC predictive risk scores in chronic hepatitis B (CHB) patients require HBV-DNA quantification which is a costly test not available in all parts of the world. Globally, the majority of CHB patients are seen in healthcare settings where only simple liver biochemistries (LBC) and ultrasound are available, thus limiting the applicability of such scores. Aim: This study aims to develop and externally validate a clinically practical

HBV-DNA-free scoring system to predict HCC in CHB patients. Methods: The development cohort comprised 673 CHB patients from our department’s outpatient clinics enrolled in a physician driven HCC surveillance program comprising 3-6 monthly LBC and AFP and 6-12 monthly imaging. They were followed up over 10 years (2003-2013). Cirrhosis was diagnosed on

histology or imaging with supportive clinical evidence. HCC was diagnosed on dynamic CT/MRI scan or histology. The validation cohorts included 2586, 449 and 318 patients from the REVEAL-HBV, Queen Mary Hospital (QMH), Hong Kong and Prince of Wales Hospital (PWH), Hong Kong respectively. Risk factors at baseline Unoprostone evaluated for HCC development included gender, age, presence of cirrhosis, HBeAg status, albumin, bilirubin, alkaline phosphatase, ALT, AST and AFP. Independent variables were gender, age, AFP level and cirrhosis. Multiple logistic regression was used to predict risk of HCC at 10 years. Results: 673 patients were enrolled with 545 (81%) still on follow-up after 10 years. Over 10 years, 43 developed HCC in the development cohort and 217 in the validation cohorts (REVEAL-134; QMH-30; PWH-53). Using a cutoff value of ≥4.5 (see table), AUROC was 0.915 (95% CI 0.880-0.949) with 88.1% sensitivity, 83% specificity and 98.8% negative predictive value (NPV) in the development cohort. AUROC were 0.767 (95% CI 0.725-0.810), 0.902 (95% CI 0.856-0.948) and 0.830 (95% CI 0.747-0.913) in the REVEAL, QMH and PWH validation cohorts respectively. Specificity and sensitivity ranged between 79.2%-95.8% and 48.5-76.7% respectively for the 3 validation cohorts and NPV varied between 93.0-97.9%.