Adams, Alberto Quaglia, Charalambos G Antoniades Background: HLH

Adams, Alberto Quaglia, Charalambos G. Antoniades Background: HLH is frequently fatal (overall mortality

>50%) and is often underdiagnosed. It involves a final common pathway of hypercytokinemia. A timely diagnosis is imperative to facilitate immunosuppressive therapy and decrease mortality. HLH presenting as severe acute hepatitis or ACLF is extremely rare and is not well recognized. We present our experience of HLH in patients presenting with severe acute hepatic insult/ liver failure. Patients and Methods: Retrospective analysis of admitted patients Cilomilast concentration with systemic inflammatory response fulfilling diagnostic HLH criteria (> 5/8).[Henter et al, 2004] Results Seventeen patients [M: F -14:3; Adults: Child- 14:3; median age- 26 years (range-1 m to 66 yrs] were diagnosed with acquired HLH at our hospital from

year 2010 to 2012. Twelve (70.6%) patients presented clinically as ACLF (n=7) and severe acute hepatitis ( n=5) at admission. Viral associated HLH (8 patients; 47.1%) was most common (HAV-3, HEV-2, EBV-1, Dengue-1, Parvovirus-1). Although, etiology remained undiag-nosed in 7(41.2%) patients, rare presentations included lym-phomatous infiltration of liver (1) & visceral leishmaniasis (1). While fever [16 patients (94.2%); median duration- 30days (4-90 days)] and jaundice [14 patients; mean bilirubin-20.34 ± 8.6mg/dl] were most common presentations, clinical signs such as presence of enlarged liver (76.4%), spleen (76.4%) and ascites (58.8%) were most frequent. Five ACP-196 concentration patients also had AKI (serum creatinine >1.5 mg/dl) at admission. Important biochemical parameters included hyperferritinemia [all patients; mean- 16,064.7 ±7,652 ng/ml], hypertriglyceridemia (10 patients; mean-355 ± 145 mg/dl), raised LDH(mean- 2,953 ± 726 IU/L) and low fibrinogen (12 patients; mean-146.1 ± 32.4 mcg/L) levels. The mean plasma haemoglobin was 8.08 ± 1.33 g/L and total leucocyte count was 2.1

x 103 /cu mm. Bone marrow aspiration was done in 12 patients; 11 of which showed the presence of hemophagocytosed histiocytes. Ten (58.8%) patients had in-hospital mortality and the main cause was eventual sepsis and multiorgan failure. 12 patients (70.6%) received specific immunosuppressive therapy (steroids-4, IV immunoglobulin -4, plasmaphersis-3, cyclosporine-1) but these therapies made no difference in clinical outcome compared to those who did selleck kinase inhibitor not receive these therapies (in-hospital mortality- 66.67% vs. 62.25%, respectively). Conclusions: HLH may masquerade as acute hepatic insult, in patients presenting with severe and rapidly progressive liver failure. It is important to suspect and recognise this generally fatal entity early enough in patients with unexplained acute hepatitis or ACLF, especially in presence of severe anemia. Disclosures: The following people have nothing to disclose: Ankur Jindal, Ashok Choudhary, Shiv K. Sarin Background/Aim The prognostic assessment of cirrhotic patients in the ICU provides short-term and controversial results.

51 Not surprisingly, patients with occult infection appear to be

51 Not surprisingly, patients with occult infection appear to be at higher risk for HBV reactivation than HBcAb positive/HBV DNA negative patients.37 The true incidence of chemotherapy-induced reactivation ACP-196 nmr of hepatitis B in these patients is uncertain. Lok and colleagues performed

a prospective study of HBV reactivation in 100 Chinese patients who received chemotherapy for lymphoma. Fifty-one of these patients had evidence of previous hepatitis B exposure (HBcAb positive with or without HBsAb). Following chemotherapy, reactivation hepatitis occurred in 4%, none of whom died, compared to 48% in patients who were HBsAg positive at the time of chemotherapy, in whom the mortality reached 8%.17 More recently, in a retrospective analysis of 319 HBcAb positive/HBsAg negative patients receiving chemotherapy for lymphoma, reactivation of hepatitis B occurred in just over 1%. However in the 74 patients in this study who received chemotherapy in combination with rituximab, the reactivation rate was 2.7%.56 There are now a number of case reports of fatal reactive hepatitis in HBcAb-positive patients who received rituximab-containing chemotherapy for lymphoma.42,46,57–59 In the setting of allogenic hematopoietic stem cell transplantation seroreversion is far X-396 more common than following standard chemotherapy; it occurs in 40% at 2 years and 70% of patients at 5 years post-transplantation.60

With selleck chemicals llc prolonged follow-up, the rate of seroreversion in one case series approached 100%.61 Patients with graft-versus

host disease appear more likely to undergo seroreversion and represent a particularly high-risk group.62 It has been proposed that a drop in HBsAb titer can identify patients at risk of seroreversion and who are likely to benefit from antiviral prophylaxis.60,63 However, this approach is not applicable to HBsAb-negative and HBcAb positive patients and remains untested in other patient populations. Reactivation has also been described in HBcAb positive/HBsAg negative patients following organ transplantation,64 although the relative risk of reactivation is low and routine anti-viral therapy is generally not used in this patient group.65 The most important first step in avoiding the serious morbidity associated with HBV reactivation is to identify patients at risk before they undergo chemotherapy. Clearly, in areas of high HBV endemicity all patients should be screened for HBsAg and HBcAb prior to immunosuppressive chemotherapy. There are many immunosuppressive therapies that carry a low risk of HBV reactivation, and are so widely used to make routine HBV screening in low risk populations impractical. These include short courses of corticosteroids alone, and widely used immunosuppressant medications such as methotrexate and azathioprine when used as monotherapy.

51 Not surprisingly, patients with occult infection appear to be

51 Not surprisingly, patients with occult infection appear to be at higher risk for HBV reactivation than HBcAb positive/HBV DNA negative patients.37 The true incidence of chemotherapy-induced reactivation selleck compound of hepatitis B in these patients is uncertain. Lok and colleagues performed

a prospective study of HBV reactivation in 100 Chinese patients who received chemotherapy for lymphoma. Fifty-one of these patients had evidence of previous hepatitis B exposure (HBcAb positive with or without HBsAb). Following chemotherapy, reactivation hepatitis occurred in 4%, none of whom died, compared to 48% in patients who were HBsAg positive at the time of chemotherapy, in whom the mortality reached 8%.17 More recently, in a retrospective analysis of 319 HBcAb positive/HBsAg negative patients receiving chemotherapy for lymphoma, reactivation of hepatitis B occurred in just over 1%. However in the 74 patients in this study who received chemotherapy in combination with rituximab, the reactivation rate was 2.7%.56 There are now a number of case reports of fatal reactive hepatitis in HBcAb-positive patients who received rituximab-containing chemotherapy for lymphoma.42,46,57–59 In the setting of allogenic hematopoietic stem cell transplantation seroreversion is far check details more common than following standard chemotherapy; it occurs in 40% at 2 years and 70% of patients at 5 years post-transplantation.60

With find more prolonged follow-up, the rate of seroreversion in one case series approached 100%.61 Patients with graft-versus

host disease appear more likely to undergo seroreversion and represent a particularly high-risk group.62 It has been proposed that a drop in HBsAb titer can identify patients at risk of seroreversion and who are likely to benefit from antiviral prophylaxis.60,63 However, this approach is not applicable to HBsAb-negative and HBcAb positive patients and remains untested in other patient populations. Reactivation has also been described in HBcAb positive/HBsAg negative patients following organ transplantation,64 although the relative risk of reactivation is low and routine anti-viral therapy is generally not used in this patient group.65 The most important first step in avoiding the serious morbidity associated with HBV reactivation is to identify patients at risk before they undergo chemotherapy. Clearly, in areas of high HBV endemicity all patients should be screened for HBsAg and HBcAb prior to immunosuppressive chemotherapy. There are many immunosuppressive therapies that carry a low risk of HBV reactivation, and are so widely used to make routine HBV screening in low risk populations impractical. These include short courses of corticosteroids alone, and widely used immunosuppressant medications such as methotrexate and azathioprine when used as monotherapy.

2C) The hepatocyte marker, CYP3A4, was down-regulated in EpCAM+

2C). The hepatocyte marker, CYP3A4, was down-regulated in EpCAM+ cells and not detected in CD90+ cells, compared with EpCAM− CD90− cells. POU5F1 and BMI1 were equally up-regulated in both EpCAM+ and CD90+ cells, compared with EpCAM− CD90− cells. EpCAM and CD90 were independently and distinctively expressed in different cellular lineages, so we evaluated the staining of EpCAM and CD90 separately and analyzed the clinicopathological characteristics of surgically resected

HCC cases. HCCs were regarded marker positive if ≥5% positive staining was detected in a given area. The existence of EpCAM+ cells selleck (≥5%) was characterized by poorly differentiated morphology and high serum AFP values with a tendency for portal vein invasion, whereas the existence of CD90+ cells (≥5%) was associated with poorly differentiated morphology and a tendency for large tumor size (Supporting Tables 2 and 3). Notably, the existence of CD90+ cells was associated with a high incidence of distant organ metastasis, including lung, bone, and adrenal gland, within 2 years after surgery, whereas EpCAM+ cell abundance appeared unrelated to distant organ metastasis. We evaluated the characteristics of EpCAM+ or CD90+ cells in seven representative HCC cell lines. Morphologically, all EpCAM+ cell

lines (HuH1, Ivacaftor chemical structure HuH7, and Hep3B) showed a polygonal, epithelial cell shape, whereas three of four CD90+ cell lines (HLE, HLF, and SK-Hep-1) showed a spindle cell shape (Fig. 3A). EpCAM+ cells were detected in 11.5%, 57.7%, and 99.6% of sorted HuH1, HuH7, and Hep3B cells, respectively. A small CD90+ cell population (0.66%) was observed in PLC/PRL/5, whereas 91.3%, 10.8%, and 59.0% of CD90+ cells were detected in HLE, HLF, and SK-Hep-1, respectively. Compared with primary HCCs, only EpCAM+ or CD90+ cells were detected in liver cancer cell lines under normal culture conditions (Fig. 3B), suggesting that these cell lines contain a relatively pure cell population most likely obtained by clonal selection through the establishment process. A class-comparison analysis with univariate t tests and a global permutation test (×10,000) of microarray data

yielded two main gene clusters up-regulated in EpCAM+ cell lines (HuH1, HuH7, selleck inhibitor and Hep3B) (cluster I, 524 genes) or in CD90+ cell lines (HLE, HLF, and SK-Hep-1) (cluster II, 366 genes) (Fig. 3C). PLC/PRL/5 showed intermediate gene-expression patterns between EpCAM+ and CD90+ cell lines using this gene set. Pathway analysis indicated that the genes enriched in cluster II were mainly associated with blood-vessel morpho- and angiogenesis (Fig. 3D). By contrast, the enriched genes in cluster I were significantly associated with known hepatocyte functions (P < 0.01) (Fig. 3E). In addition, we identified that the enriched genes in cluster II were significantly associated with neurogenesis, skeletal muscle development, and EMT.

Methods: A

Methods: A Opaganib datasheet note based retrospective review of 18 patients who had early exposure to PI at Kings College Hospital, LondonPopulation: The mean age was 53.6 (43–73) years. All the patients had experienced treatment failure

with standard therapy. 88.9% of the patients were cirrhotic, with histological confirmation in 50%. There was equal numbers of A and B subtype patients (41.2%) the rest being A/B. For IL28B polymorphisms 27.8% were CC, 61.1% CT and 11.1% were TT. 61.1% were responder relapsers, 22.2% were partial responders, 16.7% null-responders. The mean platelet count was at baseline was 147.8 (58–343) ×109/L, with 33% having a platelet count less than 10 0 × 109/L. All patients were planned for 48 weeks therapy given that all had previous treatment. 44.4% received therapy with Telaprevir and 55.5% had Boceprevir based regime. Results: 61.1% of patients completed 48 weeks of therapy. Reasons for early termination included; 22.2% stopping because of viral breakthrough, 11.1% for hepatic

decompensation and 5.6% for acute pancreatitis. The 61.1% of patients that completed 48 weeks therapy all had an end of treatment Fluorouracil solubility dmso respons. SVR was achieved in 44.4% of patients, of those who achieved end of treatment response but no SVR, one patient was lost to follow up, one had late viral breakthrough and one has not yet reached the 24 week post treatment mark. Conclusion: In

our small monocentric cohort of complex patients reasonable SVR rates were achieved with use of protease inhibitors in an expert environment. Key Word(s): 1. Real world; 2. genotype 1 HCV; 3. protease inhibitor; 4. difficult to-treat; Presenting Author: TAUFIQUE AHMED Additional Authors: ASHLEY BARNABAS, SARAH KNIGHTON, KATHRYN OAKES, AISLING CONSIDINE, ABID SUDDLE, KOSH AGARWAL Corresponding Author: TAUFIQUE AHMED Affiliations: selleck Khoo Teck Puat Hospital; Kings College Hospital NHS Foundation Trust Objective: To delineate adverse events (AEs) in difficult to treat (DTT) HCV patients treated with protease inhibitor triple therapy. Methods: A retrospective case review of all patients completing antiviral therapy at Kings College Hospital. Results: 26 patients had complete data. 84.6% were treatment experienced with 84% cirrhotic. Equal numbers of patients were treated with each protease inhibitor. During treatment 26.9% patients had a lowest recorded haemoglobin of <8 g/dL with a mean drop from baseline of 4.7 (1.9–7.2) g/dL. 46.2% required Erythropoietin, 19.2% required blood transfusion and 50% required Ribavirin dose reduction. 42.3% of patients had a lowest recorded neutrophil count < 1 cells/ml, with a mean drop from baseline of 2.11 (0.17–5.31) cells/ml and 19.2% required G-CSF. 34.

3B) Normal tissue stained

uniformly positive for the Fah

3B). Normal tissue stained

uniformly positive for the Fah protein (Fig. 3B, I), whereas it was undetectable in nodular areas (Fig. 3B II-V) except for some displaced tissue surrounding the tumor-like structures (Fig. 3B III). The hypothesis that LV-mediated insertional mutagenesis was not associated with tumor formation was supported by the fact that tumorous tissue had low copy numbers (0.01 ± 0.02) compared to histologically normal areas expressing the Fah protein (0.40 http://www.selleckchem.com/products/Nolvadex.html ± 0.04; P < 0.05) (Fig. 3C; Supporting Fig. 5). Even in the absence of hepatic tumors, LV integration could initiate clonal imbalance by activating growth promoting genes as it was demonstrated in gene therapy of the hematopoietic system.35, 36 To test for this, LV integration sites from serially transplanted hepatocytes of the in vivo (n = 25) and the ex vivo group (n = 13) were amplified by LM-PCR and 454 pyrosequencing. In a total of 296,036 sequences we identified 4,349 independent insertion sites from 38 repopulated animals, which located to 2,483 unique gene IDs (GID). Numerous insertion sites were found in all generations of serially transplanted mice with no dominant bands in agarose gel indicating a polyclonal

regeneration of the recipient livers (Fig. 4A). All vector-genome junctions located closer than 500 kb to the TSS of annotated selleck chemicals llc see more genes were included for analysis of clonality. Using LM-PCR we aimed to identify expanded cells and clonal imbalance rather than the full repertoire of insertions. The limited input of DNA for LM-PCR (0.5%-1% of total liver cells and 10% of initial DNA for nested PCRs) and the coverage using three enzymes for genome fragmentation (76.5% as determined by capture-recapture analysis (Supporting Fig. 7) reduced the overall number of detectable insertions. Based on our calculations (Supporting Fig. 6) we expected to recover around 150-200 insertion sites per repopulated

mouse liver. Averages of 109 ± 25 and 142 ± 84 unique insertion sites per liver were allocated in the in vivo and ex vivo groups, respectively (Supporting Table 4). The mean vector copy numbers of 1.70 ± 0.24 per liver were similar in all generations of serially transplanted mice (Fig. 4B). To determine potential clonal selection after serial transplantations, we calculated the number of clones contributing to 50% of all 454-reads per liver. The contribution of top 50% (T50) clones in latest-generation livers was not significantly reduced when compared to first-generation livers, either in the in vivo group (10.6 ± 1.2% and 11.6 ± 2.2%, P = 0.686) or in the ex vivo group (13.9 ± 1.4% and 12.9 ± 2.7%, P = 0.806), respectively (Fig. 4C).

Transects were located between 620 and 3495 km from the colony

Transects were located between 6.20 and 34.95 km from the colony. To establish whether jackals were territorial we observed and tracked

individuals from 12 focal groups, three in both years of the study, during daylight hours (06:00–19:30 h) over a 6-week period from early November to mid-December in 2004 and 2005. Observations were conducted using established activity conventions (P. Moehlman pers. comm.) to identify agonistic encounters (including fighting, chasing, aggressive body postures) and self-advertisement, in the form of scent-marking GDC-0449 mw and vocalizations by the dominant pair. The locations of behavioural observations were recorded using GPS. To distinguish territorial scent-markings we considered only raised-leg urinations, scratching and rubbing performed by the dominant pair in tandem (i.e. male and female scent-marked

the same site sequentially). In GPCR Compound Library most cases we could track pairs on foot and during border patrols, and record exact scent-marking locations. During border patrols the dominant pair would trot or walk along territory boundaries, frequently sniffing and tandem scent-marking, and occasionally emitting loud vocalizations. In contrast, when jackals commuted to the colony, territory holders typically travelled at a fast trot, did not scent-mark frequently and would not always travel together. At the fur seal colony communication selleck chemicals through advertisement or defensive/aggressive behaviour was usually associated with food and thus differentiated from territorial behaviour during border patrols and when individuals were located within their territory. Following Höner et al. (2005), geo-referenced observations of agonistic encounters (N=164) and self-advertisement behaviour (N=1447) were recorded, along with locations of active dens with offspring (N=60) and potential dens where repeated digging by the dominant pair

was observed (N=54). Territory size was calculated using the minimum convex polygon method (Harris et al. 1990) with Hawth’s analysis tools (Beyer, 2004) in ArcGIS v9.0 (ESRI). Within-territory density was calculated as group size divided by territory size. To aid interpretation of data on territorial behaviour and territory size we recorded number of different dens pairs utilized while pups were 0–12 weeks old and/or no longer den-dependent. We performed statistical analyses in spss (release 16.0). In examining the effects of distance on group size, highway density and within-territory density, linear regression analysis was used. Distance was log transformed for all statistical analyses to aid visual interpretation of data. To test the effect of group size, presence of subordinates, number of dens and distance on territory size a generalized linear model (GLM) with normal error structure was used. Group size was square route transformed to stabilize variance for analysis.

S1) The recordings are also from the population of mammal-eating

S1). The recordings are also from the population of mammal-eating

killer whales residing in British Columbia, and therefore may differ from those of the whales in the Bahamas. We cannot disregard the possibility that these two alterations may have been significant enough to change the whale’s perception of the stimulus, from that of a predation call to simply a novel signal. Additionally, while the Navy MFA sonar contains frequency and timing elements similar to that of killer whale predation calls, it is not an exact match. In the MFA playback, one 1.3 s MFA sonar sound was played every 25 s, while the killer whale stimulus was an actual recordings of natural sounds, often with more than one vocalization every 25 s. However, both the MFA Sotrastaurin purchase and killer whale sounds are below the best hearing range of those beaked whale species whose hearing has been measured (Cook et al. 2006). The lowered perception of signals in this frequency range may mean that the whales err on the side of caution and interpret the sonar signals in a natural behavioral context as similar to the sounds of a predator. The mismatch of some of the elements of the two signals may mean that the whales require either higher received levels or greater cumulative sound exposure levels in order to induce an antipredator reaction. While it is not possible to draw a direct connection between MFA sonar and an antipredator behavioral reaction in

M. densirostris due to the limited sample size and confounding factors, a definitive behavioral reaction has been quantified in selleck compound this experiment. Despite the confounding factors, our results do show that Blainville’s beaked whales respond to modified killer whale predation sounds with a prolonged

and directed avoidance reaction. The method developed here can be applied to movement data from future controlled exposure experiments. Further experiments should focus on differentiating between the reactions to the two stimuli. The authors acknowledge the support and involvement of numerous field participants in this project. In particular, we acknowledge Leigh Hickmott who provided click here tagging support, and Walter Zimmer for analysis of tag data. In addition, we acknowledge Ian Boyd, Christopher Clark, Diane Claridge, David Moretti, and Brandon Southall for their invaluable work conceiving of, planning, and executing this project. We thank Ari Daniel Shapiro for the initiation of the data analysis. We also thank Volker Deecke for providing the recordings of killer whales used as a playback stimulus. The authors acknowledge the support of the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) in the completion of this study. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. This research was conducted under permits for marine mammal research issued by the U.S.

7,8 This review focuses on the relationships between the 3 classe

7,8 This review focuses on the relationships between the 3 classes of drugs known to be involved in severe SS, and the relative degrees of toxicity they characteristically precipitate. A key point to be emphasized is the spectrum concept of SS. SS is a synaptic serotonin (5-HT) concentration-related phenomenon.9 Readers are referred to recent selected reviews of SS for a broader perspective. There have been advances in the quantification of the frequency

and severity of SS with different drugs,9-14 in the definition of SS in animals and humans,15-17 in the pathophysiology,15 in the clinical presentation,18 and in its management and treatment.19-21 Serotonin syndrome can be diagnosed with accuracy and confidence, but few reports classify it using recognized diagnostic criteria, hence diminishing their value. It is not, as far as PD0332991 concentration current human and animal evidence indicates, an idiosyncratic response, but a predictable and inevitable Selleckchem Midostaurin result of

toxicity (mediated via the final common pathway of elevated intra-synaptic serotonin). If a case history were to appear reporting SS following an overdose of vitamin C, it would be parsimonious to assume that there had been a failure to ascertain or recognize the simultaneous ingestion of a potently serotonergic drug, cf. the Stanford case report.22 It would not be logical to make an initial assumption that vitamin C had previously unknown serotonergic properties, especially as we have good reasons to predict that it does not affect serotonin. That is Bayesian reasoning, ie, considering the prior probability when

estimating the likelihood of an outcome. Without such frameworks of knowledge and understanding of SS, case reports are often difficult to interpret, and the type of information they can yield reliably requires cautious consideration.23 The uncertainty and debate surrounding triptans demonstrates this problem clearly. The FDA alert was based on case reports, most of them informal, or “second-hand” and not peer-reviewed, and interpreted with an imperfect notion of selleck kinase inhibitor the symptoms and pathophysiology of SS, and without using validated criteria to establish diagnoses (eg, the Hunter Serotonin Toxicity Criteria [HSTC]17,20). The HSTC demonstrate unequivocally that clonus is the single most important sign required to diagnose SS, a fact that has now been established for many years, yet case reports of SS rarely, if ever, document the presence, or absence, of this sign. When such key information is lacking, little credence can be given to many reports. Case reports constitute a low grade of evidence, but they command undue attention and are repeatedly cited, even when they have been firmly rebutted (for just such an error that occurs in the FDA case reports, see24,25). The 3 classes of therapeutic drugs that, in certain combinations at usual doses, have been reliably documented to be capable of precipitating severe SS are: monoamine oxidase inhibitors (MAOIs), SRIs, and releasers.

DNA was isolated from 103 archival blood samples for genotyping s

DNA was isolated from 103 archival blood samples for genotyping seven polymorphisms in

genes that influence vitamin D status (NADSYN1, DHCR7, GC, CYP2R1 and VDR), together with PNPLA3 which has a known association with NAFLD. Biopsies were scored by a liver histopathologist according to the Rucaparib Kleiner/Brunt system. Vitamin D seasonality was normalised using the Sachs model. RESULTS: Cycling of 25(OH)D levels throughout the year was evident, with the majority of samples in the deficient (UK Department of Health; <25nmol/l [31.8%]) or insufficient (USA Institute of Medicine; <50nmol/l [84.1%]) ranges. Patients had significantly lower 25(OH)D levels in winter months when compared to spring, summer and autumn months (p=0.006; p=0.0001; p=0.0001 respectively). In Caucasian patients, the PNPLA3 G allele was associated with increased steatosis (p=0.01) and inflammation (p=0.026). For SNPs related to vitamin D metabolism, presence of the NADSYN1 A allele, DHCR7 G allele and VDR A allele Fulvestrant datasheet were all independently associated with increased steatosis (p=0.04; p=0.01; p=0.01 respectively), while the GC A allele was associated with increased inflammation (p=0.028) in Caucasian patients. No association between the GC rs2282679, rs7041 and CYP2R1 rs10741657 polymorphisms

and NAFLD histo-logical severity was found. CONCLUSIONS: This is the first study, to our knowledge, to investigate vitamin D status and key polymorphisms related to vitamin D metabolism in a paediatric NAFLD population. Patients had very low winter vitamin D status, and were in the insufficient

range throughout the entire click here year. Our novel finding that polymorphisms in four key genes determining vitamin D status were associated with NAFLD his-tological severity warrants further investigation. Disclosures: The following people have nothing to disclose: Philippa S. Gibson, Emer Fitzpatrick, Alberto Quaglia, Anil Dhawan, Huihai Wu, Kathryn Hart, Susan Lanham-New, J Bernadette Moore Background: The ductal plate harbors hepatic progenitors, cholangiocytes and periportal hepatocytes. Jag1+/−Rfng+/−livers have been identified with abnormal remodeling of the ductal plate including aberrant differentiation of Sox9+ progenitors. We sought to better define the Sox9 population in the one-week old Jag1+/−Rfng+/− portal tracts using laser capture technology and microarray analysis. Methods: Five control and Jag1+/−Rfng+/− livers were snap frozen and sectioned at 12 μM thickness under RNAse-free conditions and RNA prepared. Following Agilent analysis for RIN quality, RNAs were converted to cDNA and amplified using the Ovation Pico WTA System V2 kit (NuGEN Technologies, San Carlos, CA). Templates were labeled and hybridized using the GeneChip® Mouse Gene 2.0 ST Arrays (Affymetrix, Santa Clara, CA).