We next explored whether dual-vector therapy could restore CTL responses by detecting the percentages and activation status of liver-resident NK, CD4+ T, and CD8+ T cells in HBV+ mice. While no significant changes were detected in hepatic CD4+ T, NK and NKT cells (Supporting Fig. 6), the percentage and absolute number of hepatic CD8+ T cells and activating CD8+ T cells were markedly up-regulated by dual-vector administration (Fig. 5A,B). Furthermore, dual-vector treatment markedly augmented CTL function (e.g., CD107a+ and IFN-γ+ CD8+ T-cell percentages increased) in liver compared to ssRNA vector Selleck Ibrutinib (Fig.

5C), along with down-regulation of PD-1 and up-regulation of CD28 (Fig. 5D), suggesting that dual therapy reverses CD8+ T-cell anergy by regulating the PD-1/CD28 axis. Moreover, the percentages of HBV-specific hepatic CD8+ T cells as well as HBV-specific CD107a+ and IFN-γ+ CD8+ T cells were also significantly enhanced by dual-vector treatment (Fig. 5E). In addition, we also observed the T-cell responses in spleen and peripheral blood and found similar results in line with the microenvironment. As shown in Supporting Fig. 7, the percentages and absolute numbers of CD8+ T cells

as well as activated CD8+ T cells in both spleen and peripheral blood increased after dual vector therapy, suggesting Alpelisib that the restoring of CD8+ T-cell response exerted by dual vector is systemic. To further explore the role of CD8+ T cells, we depleted them from HBV+ mice with an anti-CD8β mAb. CD8+ T cells, but not CD4+ T, are critical for dual-vector-mediated inhibition of HBV replication, as HBV DNA copies, HBx expression, and HBsAg levels

in serum became significantly higher, while serum IFN-γ levels declined, MCE after CD8+ T-cell depletion (Fig. 6A,B). NK cell-depletion also partly attenuated dual-vector-mediated inhibition of HBV, suggesting that NK cells might also participate in dual-vector-mediated HBV inhibition. But the role of CD8+ T cells was the most prominent. To determine the role of CD8+ T cells, we adoptively transferred splenic CD8+ T cells or CD8+ T-cell-depleted splenic lymphocytes from wild-type (WT) mice into HBV+ Rag-1−/− mice. Adoptively transferring CD8+ T cells but not non-CD8+ T cells or IFN-γ−/− CD8+ T-cells (e.g., CD8+ T cells from IFN-γ−/− mice) inhibited HBV replication (serum HBsAg) in HBV-persistent Rag-1−/− mice when dual vector treatment was used (Fig. 6C). Although dual vector promoted CD8+ T cell activation, HBsAg inhibition was markedly impaired in HBV-persistent IFN-γ−/− mice (the inhibitory rate is 85.16 ± 4.75% and 55.24 ± 10.43% in WT HBV+ and IFN-γ−/− HBV+ mice, respectively) (Fig. 6D). These results suggest that recovering anti-HBV adaptive immunity by reversing hepatocyte-intrinsic tolerance is at least partially dependent on functional rescue by IFN-γ-producing CD8+ T cells.

We next explored whether dual-vector therapy could restore CTL responses by detecting the percentages and activation status of liver-resident NK, CD4+ T, and CD8+ T cells in HBV+ mice. While no significant changes were detected in hepatic CD4+ T, NK and NKT cells (Supporting Fig. 6), the percentage and absolute number of hepatic CD8+ T cells and activating CD8+ T cells were markedly up-regulated by dual-vector administration (Fig. 5A,B). Furthermore, dual-vector treatment markedly augmented CTL function (e.g., CD107a+ and IFN-γ+ CD8+ T-cell percentages increased) in liver compared to ssRNA vector Ibrutinib nmr (Fig.

5C), along with down-regulation of PD-1 and up-regulation of CD28 (Fig. 5D), suggesting that dual therapy reverses CD8+ T-cell anergy by regulating the PD-1/CD28 axis. Moreover, the percentages of HBV-specific hepatic CD8+ T cells as well as HBV-specific CD107a+ and IFN-γ+ CD8+ T cells were also significantly enhanced by dual-vector treatment (Fig. 5E). In addition, we also observed the T-cell responses in spleen and peripheral blood and found similar results in line with the microenvironment. As shown in Supporting Fig. 7, the percentages and absolute numbers of CD8+ T cells

as well as activated CD8+ T cells in both spleen and peripheral blood increased after dual vector therapy, suggesting Small molecule library ic50 that the restoring of CD8+ T-cell response exerted by dual vector is systemic. To further explore the role of CD8+ T cells, we depleted them from HBV+ mice with an anti-CD8β mAb. CD8+ T cells, but not CD4+ T, are critical for dual-vector-mediated inhibition of HBV replication, as HBV DNA copies, HBx expression, and HBsAg levels

in serum became significantly higher, while serum IFN-γ levels declined, 上海皓元 after CD8+ T-cell depletion (Fig. 6A,B). NK cell-depletion also partly attenuated dual-vector-mediated inhibition of HBV, suggesting that NK cells might also participate in dual-vector-mediated HBV inhibition. But the role of CD8+ T cells was the most prominent. To determine the role of CD8+ T cells, we adoptively transferred splenic CD8+ T cells or CD8+ T-cell-depleted splenic lymphocytes from wild-type (WT) mice into HBV+ Rag-1−/− mice. Adoptively transferring CD8+ T cells but not non-CD8+ T cells or IFN-γ−/− CD8+ T-cells (e.g., CD8+ T cells from IFN-γ−/− mice) inhibited HBV replication (serum HBsAg) in HBV-persistent Rag-1−/− mice when dual vector treatment was used (Fig. 6C). Although dual vector promoted CD8+ T cell activation, HBsAg inhibition was markedly impaired in HBV-persistent IFN-γ−/− mice (the inhibitory rate is 85.16 ± 4.75% and 55.24 ± 10.43% in WT HBV+ and IFN-γ−/− HBV+ mice, respectively) (Fig. 6D). These results suggest that recovering anti-HBV adaptive immunity by reversing hepatocyte-intrinsic tolerance is at least partially dependent on functional rescue by IFN-γ-producing CD8+ T cells.

Joyce – Independent Contractor: Venebio Group, LLC; Management Position: Venebio Group, LLC Hidekazu īsukamoto – Consulting: Shionogi & Co., S. P. Pharmaceutics; Grant/Research Support: The Toray Co. Arun J. Sanyal – Advisory Committees or Review Panels: Gore, Gilead, Abbott, Ikaria; Consulting: Salix, Immuron, Exhalenz, Bayer-Onyx, Genentech, Norgine, GalMed, Novartis, Echosens, Takeda; Grant/Research

Support: Salix, Genentech, Genfit, Intercept, Ikaria, Takeda, Gilead; Independent Contractor: UpToDate The following people have nothing to disclose: Jun Xu, Faridoddin Mirshahi, Hae K Min, Tommy Pacana, Vaishali Patel, Kalyani Daita, Kim Ekroos Background: Galectin-9 (Gal-9), predominantly expressed by activated Kupffer cells, has recently been demonstrated to be important for pro-inflammatory cytokine responses OSI-906 mouse as well as regulatory T cell (Treg) expansion within the liver. Recent data (Almeida J, 2013, PMID: 23550693) demonstrate that Tregs are significantly decreased in patients with alcoholic hepatitis. Moreover, as ample evidence indicates that inflammation is

Alisertib supplier central to the pathogenesis of ALD, we explored whether genetic polymorphisms of Gal-9 would associate with development of ALD. Methods: Genomic DNA samples from 375 patients with ALD were studied; 179 subjects with excessive alcohol intake who did not develop ALD served as controls (Acon). Based on Hapmap, we performed genotyping for 5 Gal-9 SNPs tagging the most common haplotypes. As shown in the Table below, Rs732222, Rs3751093, Rs4239242, Rs4239242 were all associated with protection against development of ALD. The H3 haplotype was less common in ALD (〇R 0.68, p = 0.016). Next, PBMCs from normal subjects with no significant medchemexpress history of alcohol consumption were stimulated with IFN-y 25 ng/ml and Et〇H 25 nM for 24 hrs and subject to RT-PCR. Compared to media, this stimulation yielded significant upregulation of Gal-9 (p = 0.0078). The SNPs

Rs4239242 and Rs4794976 correlated with higher transcription of Gal-9 and no difference between TNF- α(as a control). The H3 haplotype (GGGTT, ALD 133, Acon 86; p=0.016, 〇R 0.68) was also associated with higher Gal-9 transcription compared to H1(GAGTT)/H1 and H1/H3. Conclusions: In a targeted SNP approach, we found that genetic variation within the galectin-9 gene is associated with the risk of developing liver disease in patients with alcoholism as compared to alcoholics who do not develop liver disease. These data suggest functional correlates of Gal-9 SNPs, perhaps by expansion of Tregs as a protective mechanism. ALD Acon Odds ratio RS732222 GG 198 112 GA 159 57 1. 49 (1. 04-2. 15) P=0.035 AA 18 10 RS3751093 GG 217 123 GA 155 53 1. 52 (1. 06-2. 20) P=0.028 AA 12 9 RS4239242 TT 138 92 TC 194 74 1. 72 (1. 21-2. 46) P=0.0034 CC 46 19 RS4794976 TT 153 97 TG 196 67 1. 66 (1. 17-2. 34) P=0.0065 GG 29 19 Disclosures: Christopher P.

Joyce – Independent Contractor: Venebio Group, LLC; Management Position: Venebio Group, LLC Hidekazu īsukamoto – Consulting: Shionogi & Co., S. P. Pharmaceutics; Grant/Research Support: The Toray Co. Arun J. Sanyal – Advisory Committees or Review Panels: Gore, Gilead, Abbott, Ikaria; Consulting: Salix, Immuron, Exhalenz, Bayer-Onyx, Genentech, Norgine, GalMed, Novartis, Echosens, Takeda; Grant/Research

Support: Salix, Genentech, Genfit, Intercept, Ikaria, Takeda, Gilead; Independent Contractor: UpToDate The following people have nothing to disclose: Jun Xu, Faridoddin Mirshahi, Hae K Min, Tommy Pacana, Vaishali Patel, Kalyani Daita, Kim Ekroos Background: Galectin-9 (Gal-9), predominantly expressed by activated Kupffer cells, has recently been demonstrated to be important for pro-inflammatory cytokine responses KU-57788 chemical structure as well as regulatory T cell (Treg) expansion within the liver. Recent data (Almeida J, 2013, PMID: 23550693) demonstrate that Tregs are significantly decreased in patients with alcoholic hepatitis. Moreover, as ample evidence indicates that inflammation is

XL184 central to the pathogenesis of ALD, we explored whether genetic polymorphisms of Gal-9 would associate with development of ALD. Methods: Genomic DNA samples from 375 patients with ALD were studied; 179 subjects with excessive alcohol intake who did not develop ALD served as controls (Acon). Based on Hapmap, we performed genotyping for 5 Gal-9 SNPs tagging the most common haplotypes. As shown in the Table below, Rs732222, Rs3751093, Rs4239242, Rs4239242 were all associated with protection against development of ALD. The H3 haplotype was less common in ALD (〇R 0.68, p = 0.016). Next, PBMCs from normal subjects with no significant MCE公司 history of alcohol consumption were stimulated with IFN-y 25 ng/ml and Et〇H 25 nM for 24 hrs and subject to RT-PCR. Compared to media, this stimulation yielded significant upregulation of Gal-9 (p = 0.0078). The SNPs

Rs4239242 and Rs4794976 correlated with higher transcription of Gal-9 and no difference between TNF- α(as a control). The H3 haplotype (GGGTT, ALD 133, Acon 86; p=0.016, 〇R 0.68) was also associated with higher Gal-9 transcription compared to H1(GAGTT)/H1 and H1/H3. Conclusions: In a targeted SNP approach, we found that genetic variation within the galectin-9 gene is associated with the risk of developing liver disease in patients with alcoholism as compared to alcoholics who do not develop liver disease. These data suggest functional correlates of Gal-9 SNPs, perhaps by expansion of Tregs as a protective mechanism. ALD Acon Odds ratio RS732222 GG 198 112 GA 159 57 1. 49 (1. 04-2. 15) P=0.035 AA 18 10 RS3751093 GG 217 123 GA 155 53 1. 52 (1. 06-2. 20) P=0.028 AA 12 9 RS4239242 TT 138 92 TC 194 74 1. 72 (1. 21-2. 46) P=0.0034 CC 46 19 RS4794976 TT 153 97 TG 196 67 1. 66 (1. 17-2. 34) P=0.0065 GG 29 19 Disclosures: Christopher P.

IL-23 induces γδ T cells to secrete IL-17A in vitro, and blocking IL-23 or IL-23 deficiency decreases the IL-17A levels in vivo (Figs. 5C, 6). Although acetaminophen increased IL-1β production, blocking IL-1β with IL-1RA had no significant effect on neutrophil infiltration (data not shown). IL-1β alone did not induce γδ T cell production of IL-17A in vitro; however, IL-1β synergized

with IL-23 to further increase IL-17A production, implying that IL-1β also plays a role in IL-17A production by γδ T cells. Because other studies have shown that IL-17A can stimulate Selleck KPT 330 macrophages to produce the inflammatory cytokines and chemokines,42, 43 further research on the interaction between macrophages and γδ T cells is required. Although γδ T cells dominantly produce IL-17A in this study, other immune cells, such as CD8+T cells, neutrophils, and lymphoid tissue inducer-like cells, also can produce IL-17A.18 Their roles in pathogenesis need to be further Ipilimumab concentration investigated. Meanwhile, whether

other cell types are involved in liver injury in other ways also needs to be studied. In summary, our study provides evidence that the macrophage-γδ T-neutrophil cascading response is involved in acetaminophen-induced liver inflammation by way of an HMGB1-TLR4-IL-23-IL-17A axis. Whether this mechanism extends to sterile inflammation other than drug-induced liver injury requires further study. The development of new therapeutic approaches that control DAMP-induced liver injury is important. The authors thank professors Zhexiong Lian, Zhinan Yin, and Shaobo Su for providing gene-deficient mice. Additional Supporting Information may be found in the online version of this article. “
“Gastrointestinal (GI) foreign bodies include food impactions, non-food foreign body ingestions and insertions per rectum, and iatrogenic foreign bodies. Although the majority of GI foreign bodies result in a relatively benign course, it has been estimated

that 上海皓元医药股份有限公司 approximately 1500–2500 deaths occur each year due to GI foreign bodies. Flexible endoscopy has become the primary diagnostic and therapeutic tool for foreign bodies of the GI tract, and knowledge of which patients need intervention and the correct timing of intervention is crucial. “
“Aim:  Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct-ligated rats, which develop HPS by 5 weeks after surgery. Methods:  A total of 96 Sprague–Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham-operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions.

It has been a major change in policy the last 6 years to publish more editorials, and we have averaged over 3 each issue during my tenure as Editor-in-Chief. While not many are highly cited

(Table 1), informal MLN8237 nmr feedback indicates JGH Editorials are well read and often appreciated for the incisive insights provide by an expert into a rapidly changing field. Editorials also provide an important learning opportunity for new writers, often fellows or junior faculty who can develop their skills in biomedical publishing in these 1100 word pieces, as well as usefully extending their personal bibliography. Reviews also contribute importantly to the growth of a journal, as they tend to be cited more often than original articles. In JGH, median citations for invited reviews are in the range of 5–6, while Consensus Guidelines are over-represented amongst the annual list of most-cited articles (typically cited > 25 times in the first 12 months after they are published). Among the numerous postgraduate

students, overseas and Australian Clinical Fellows I have had the privilege to supervise and act as mentor, GS-1101 I have often encouraged authorship of reviews for JGH, usually acting as the senior author to provide balance on content, ensure quality and a good standard of writing. Several of these reviews have been important articles for JGH, such as those included in Table 1. As Editor-in-Chief, I have also encouraged a policy of running series of high-quality reviews solicited from authors who are experts in their field. These are most often drafted (as first author) by their younger associates and trainees. The original series were developed to cover specific topics: epidemiology, hepatitis combined infections and treatment advances, complications of cirrhosis, advances in endoscopy, basic

science. During the last 2 years, solicited reviews have been consolidated in two regular MCE series: Advances in Clinical Practice, and Mechanisms of Disease. All Editors are encouraged to suggest topics and authors for these articles, and we also welcome ideas from interested potential authors. One tip for graduate students who are reading this column, if you have written an excellent introduction to your thesis on the recent advances in a particular field, discuss with your supervisor whether it is worth considering publication of this as a review article, and then let one of the Editors know of your intention. One of the articles in Table 1 cited > 200 times and many more arose from such an enquiry. In the early years, many authors (including my own team) could have been guilty of regarding JGH as a place to publish interesting clinical series or minor advances in experimental research that are unlikely to be accepted by a more established, higher impact journal.

Among

the 337 isolates collected, the overall gene diversity was moderate ( = 0.216). The level of multilocus genotypic diversity was higher within populations than among them. All individuals had unique multilocus genotypes. Genetic differentiation was significant among populations in localities, but at a moderate level (θ = 0.12; P < 0.001), suggesting that gene flow is occurring among populations. The isolates from all twelve clusters produced by Structure were found in all local populations, although at different frequencies. Therefore, the inferred clusters did not represent geographical populations. Although the null hypothesis of random mating in Rcc populations was rejected, the high level of genotypic diversity suggests that the Rcc population structure appears to be generated by a

mixed reproductive system including both asexual and sexual reproduction, along with a rather high migration rate. “
“Sensitivity monitoring studies Tamoxifen using detached leaf tests with isolates of Podosphaera leucotricha showed no adaptation to pyraclostrobin in the last years. Sequence analysis of the target AZD4547 cost gene of QoIs, cytochrome b, of different isolates of P. leucotricha showed the presence of an intron directly after codon 143. This makes the occurrence of the G143A mutation unlikely. On the other hand, intron sequences have not been detected in immediate vicinity to the codons 129 and 137; therefore, the occurrence of those two mutations cannot be excluded. As the effects of these mutations on field performance MCE on QoI fungicides are rather low, the overall resistance risk of P. leucotricha to this

fungicide class is estimated to be low. The amplified cytochrome b gene fragments (exons and introns) for samples from different European countries and Australia were highly conserved. “
“Groundnut is commonly consumed in its roasted form by many Nigerians. This study was therefore conducted to determine the levels of aflatoxin in roasted groundnut retailed in south-western Nigeria with a view to assessing the fitness of the processed nut for human consumption. The effects of roasting and de-coating as alternative methods for reducing the ‘aflatoxin scare’ in the nut were further assessed on aflatoxigenic fungal load and aflatoxin content of the nuts. Forty-eight samples of retailed raw and roasted groundnut were collected and assessed by mycological and thin-layer chromatographic analysis for changes in aflatoxigenic fungal population and aflatoxin concentration, respectively. Consequently, 480 isolates of the Aspergillus section Flavi group, A. flavus L strain (n = 410), A. tamarii (n = 56), A. parasiticus (n = 7) and A. parvisclerotigenus (n = 7), were recovered from all samples. Aflatoxigenic isolates of A. flavus L strain (58.8%) had a significantly (P < 0.05) higher incidence than the non-aflatoxigenic isolates (41.2%). Aflatoxins were detected in 43 (89.

To define reasons for the characteristic observation of active DNA synthesis but not cell division in residual hepatocytes in liver explants after ALF, we studied the effects of APAP on HuH-7 cells, mouse hepatocytes and intact mice. C57BL/6 mice were given LD50 dose of APAP i.p to induce ALF. Liver injury was characterized by encephalopathy,

liver test abnormalities, hepatic inflammation and perivenous necrosis, and mortality. Culture of HuH-7 cells or mouse hepatocytes with APAP in IC50 concentrations caused cytotoxicity as confirmed by MTT assays. Gene expression arrays from APAP-treated cells or mice showed disturbances in ATM signaling pathway and western blot of tissue and cell lysates confirmed ATM-related DNA damage responses (DDR), including pATM, pATR, pH2AX, pChek1 and pChek2 expression. ACP-196 order This DDR in the setting of ATM dysregulation was verified by Comet

assays with extensive double-strand DNA breaks. To evaluate greatest susceptibility of cell subpopulations to APAP, we analyzed HuH-7 cells by FACS, and found cells in S or G2/M were lost within 4 h, whereas cells in G0/G1 survived over long-term. This was confirmed when HuH-7 cells synchronized by hydroxyurea in late S were rapidly destroyed by APAP. By contrast, G0/G1 cells exposed to APAP stopped proliferating and failed to enter cell cycle, CYC202 despite removal of APAP from culture medium. These cells in G0/G1 displayed significant DNA damage, as indicated by gene expression arrays, pH2AX staining and Comet assays. Next, to determine whether APAP-induced arrest 上海皓元医药股份有限公司 of cell cycle could be reversed by G-CSF, which was previously found to improve outcomes in ALF, we performed further studies. Remarkably, after G-CSF treatment, HuH-7 cells exposed to APAP regained the ability to overcome

G0/G1 arrest and entered the cell cycle. Similarly, mice treated with G-CSF after induction of APAP toxicity showed improved survival and superior liver regeneration, with greater Ki67 expression compared with mice receiving APAP alone. This improvement correlated with less pH2AX staining and comet formation, indicating decreased DNA damage in G-CSFtreated animals. Conclusions: Actively cycling cells in S or G2/M were highly susceptible to APAP toxicity. By contrast, G0/G1 cells survived APAP-induced DNA damage but were prevented from cycling. The inability to reenter cell cycle will help explain failure of residual hepatocytes to regenerate liver in APAP-induced ALF. This molecular process should offer further new directions for therapeutic development in ALF. Disclosures: The following people have nothing to disclose: Preeti Viswanathan, Sriram Bandi, Sanjeev Gupta Background: Liver enlargement, due to accumulation of lipids and proteins in hepatocytes is common in heavy drinkers.

Cholesterol homeostasis in humans is the consequence of the fine regulatory mechanisms involving intestinal absorption and hepatic de novo synthesis,

as well as biliary secretion and fecal excretion of cholesterol. In enterocytes, sterol uptake and secretion is mediated by two brush border transport proteins. The Niemann-Pick C1-like 1 protein (NPC1L1) acts as an intestinal sterol influx transporter that actively facilitates the uptake of cholesterol.9-11 Two ATP-binding cassette (ABC) transporters, ABCG5 and ABCG8, work as CB-839 a heterodimeric efflux pump, for mediating cholesterol transport back to the intestinal lumen. Because in humans both NPC1L1 and ABCG5/G8 are also expressed in the hepatocyte at the canalicular membrane, both transporters contribute to the overall balance of cholesterol

absorption/secretion at two different sites: intestine and liver.12, 13 Where exactly excess biliary cholesterol comes from (i.e., intestinal absorption, hepatic de novo synthesis, reverse cholesterol transport by high-density lipoprotein [HDL]) is still an open issue and should be interpreted together with the function of these cholesterol transporters at different levels. Krawczyk et al. suggested that, at least in their particular setting, reduced cholesterol absorption, which is associated with increased cholesterol synthesis, may drive impaired cholesterol homeostasis in gallstone disease, with higher cholesterol clearance. The authors also speculated that the early events might be the biliary/intestinal cholesterol Neratinib cell line efflux (sterol clearance) followed by increased synthesis of cholesterol, since they did not occur simultaneously. MCE Overall, however, such events should result in “sustained” rather than “fluctuating” supersaturation of bile with cholesterol. Genetic factors and LITH genes play a role in the pathogenesis of cholesterol gallstones.10 In principle, a gain-of-function of ABCG5/G8 in humans might recapitulate

both steps, leading to decreased intestinal absorption versus increased biliary output of cholesterol. The ABCG8 p.D19H and p.T400K coding variants might play a role as putative susceptibility variants for gallstone formation in humans.14-16 Despite much evidence in this respect, the authors could not confirm such an interesting hypothesis, possibly due to the small cohort size. The issue becomes even more intriguing when considering that high cholesterol content is typical of Westernized diets and that the small intestine is a unique organ providing dietary and reabsorbed biliary cholesterol to the body.9 Furthermore, high efficiency of intestinal cholesterol absorption may occur, as shown in several inbred strains of mice.

37, p = 0.020), and baseline ALT > 45 for males and > 30 for females (HR 2.26, p < 0.0001) were significant predictors of treatment initiation, but not practice setting. Similarly,

only older age (HR 1.02, p < 0.0001), male gender (HR 1.42, p = 0.019) and baseline ALT > 45 for males and > 30 for females (HR 2.81, p < 0.0001) were significant independent predictors of starting treatment within the first year of treatment eligibility and not practice setting. Conclusion: The majority of patients who started treatment started within one year of becoming treatment eligible; however, approximately 40% of patients still have not started treatment on longer follow-up. Further studies are needed to determine the barriers for treatment initiation in diverse practice settings. Disclosures: Huy N. Trinh - Advisory Committees or Review Panels: BMS, Gilead; Grant/ Research Support: check details BMS, Gilead; Speaking and Teaching: BMS, Gilead, vertex; Stock Shareholder: Gilead Huy A. Nguyen – Advisory Committees or Review Panels: Gilead, BMS; Speaking and Teaching: Gilead Mindie H. Nguyen – Advisory Committees or Review Panels: Bristol-Myers Squibb, Bayer AG, Gilead, Novartis, Onyx; Consulting: Gilead Sciences, Inc.; Grant/Research Support: Gilead Sciences, Inc., Bristol-Myers Squibb, Novartis Osimertinib solubility dmso Pharmaceuticals, Roche Pharma AG, Idenix, Hologic, ISIS The following people have nothing to disclose: Vinh

D. Vu, Ailinh Do, Nghia H. Nguyen, Lily H. Kim, Khanh Nguyen Background. Fibrosis-regression(FR) rate in treated CHB-patients patients was similary estimated using Fibrotest and LSM (Fibros-can),

although with possible overestimation of FR by LSM related to necroinflammatory activity(NIA).(AntivirTher2009,2010) Aims. To prospectively evaluate : 1)The histological impact of strong inhibitor of HBV-replication, entecavir-motherapy [0.5mg/day], using Fibrotest-Actitest and LSM.2) The impact of presumed steatosis(Steatotest) on the treatment response. Methods. NUC-naïve CHB preincluded [19-centers,France] fol-lowed-up (FU) medchemexpress from baseline to M6,M12 and M24-months. Viral-response(VR) defined as undetectable-HBVDNA. Results. N=177 pre-included, 15-retracted, 3-died, 5 non-applicable Fibrotest (4 flare-up ALT>600IU/L), 24 lost-of-follow-up (FU); N=137 with M6-FU included [age 45(20-83)yrs; 71%males; 84% anti-HBe(+); 43%caucasian/29%asian/28%african]. Applicable-LSM vs Fibrotest 95%vs97.2%(p<0.0001). Fibro- test presumed advanced fibrosis(AF,F2F3F4-METAVIR) in 36%(60/167) and cirrhosis 12%(N=20/167); presumed NIA (Actitest) in 74%(123/166) and baseline steatosis>1% (Steatotest) 37%(57/156). N=43 had liver biospy [size 24(5-40)] AF 56%(24/43). VR prevalences were 67% M6(N=120), 83% M12(N=105) and 86%M24(N=50). Presumed NIA [Actitest] regressed from M0 0.38(0.02) to M6 0.21(0.01), M12 0.19(0.01) and M24 0.14(0.02), all p<0.0001vsM0. 76% patients with baseline-NIA regressed at M6. Presumed AF [Fibrotest] regressed from M0 0.69(0.02) vs M6 0.59(0.03) vs M12 0.57(0.03), M24 0.