02 mg dexametha-sone/kg) or vehicle (PBS). At termination of the study, the liver condition was evaluated by liver weight, NAFLD Activity Score (NAS), fibrosis, and paraclinical liver parameters. Result: The fructose-rich GDC-0068 research buy diet induced marked signs of NASH (increased liver weight, hepatocyte

balloning, inflammation, pericellular and perivenular fibrosis and glycogen deposition). The NAFLD Activity Score (NAS) was strongly reduced in the group of rats treated with anti-CD163-dexamethasone conjugate compared to the vehicle group and the dexamethasone group, respectively (Table 1). Further, aspartate aminotransferase levels were significantly lower in rats treated with anti-CD163-dexametha-sone compared to the vehicle group. Conclusion: Targeting of macrophages by the anti-CD163-dexamethasone conjugate significantly reduced NASH changes compared to free dexa-methasone. Thus, low-dose targeting of dexamethasone to CD163-positive macrophages is a potential future macrophage specific NASH therapy without the serious and problematic side effects seen in conventional systemic glucocorticoid therapy. Disclosures: Jonas H. Graversen – Management Position: Affinicon; Stock Shareholder: Affin-icon Henning Gronbaek – Grant/Research Support: Novartis, Ipsen Holger J. Møller – Grant/Research Support:

Danish Council selleckchem for Strategic Research; Independent Contractor: IQ-Products, NL; Patent Held/Filed: Aarhus University; Stock Shareholder: Affinicon Aps Søren K. Moestrup – Stock Shareholder: Affinicon The following people have nothing to disclose: Pia Svendsen, Hendrik V. Vilstrup Background: Emerging evidence implicates the molecular circadian clock as a critical regulator of alcoholic liver injury. Melatonin, an endogenously produced neurohormone secreted by the pineal gland, has a variety of protective effects during organ injury including promotion of cellular proliferation and differentiation. However, its effect and mechanism on the circa-dian clock learn more during alcoholic liver injury remains

to be explored. The objective of this study was to evaluate the role of mela-tonin regulated microRNA-clock gene network in alcohol-induced hepatic steatosis. Methods: The miRNA expression of melatonin upstream enzymes, serotonin N-acetyltransferase (AANAT) and N-acetylserotonin O-methyltransferase (ASMT), were assessed in ethanol and LPS treated human hepatocytes (N-Heps) and cholangiocytes (H69), as well as in 5-week chronic alcohol fed mouse liver specimens with anti-miRNA vivo-morpholino treatment and control liver tissue by real-time PCR assay. The secretion of melatonin was verified by ELISA assay. Cell proliferation and survival was measured by MTS assay. The hepatic expressions of the clock circadian genes including PER1, Clock and CRY1 were also determined by real-time PCR assay.

Disclosures: The following people have nothing to disclose: Bonnie A. Ewald, Alysse G. Wurcel, Sonali Paul, Kathleen Viveiros BACKGROUND: Subsaharan Africa (SSA) has one of the highest global rates of HCV infection, accounting for nearly 20% of all global cases. However, little is known about the population level epidemiology, including the predominant risk factors for transmission. Such information is necessary to help guide screening and management guidelines, especially with the increasing availability of effective anti-virals. METHODS: We conducted

a case-control study of prior blood donors at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana to identify risk factors and potential transmission mechanisms of HCV. KATH is a tertiary referral selleck chemicals llc hospital, receiving patients from across Ghana. A series of 180 consecutive cases that tested positive with the HCV rapid screen assay (RSA) were matched to 183 negative donors. New blood samples were taken to confirm HCV infection, assess for co-infections and an extensive survey administered to identify risk factors for infection. HCV testing including HCV Antibody confirmation, HCV quantitative viral load testing, as well as HBV and HIV serologic assessment. RESULTS: 87 individuals were identified as true infections after repeat serologic evaluation. There was no difference AZD1208 clinical trial in age and gender between infected

and non-infected individuals. HCV infected individuals were more often born at home, have tribal scarring, and circumcision selleck outside of a clinic or hospital setting. There was also a significant association with HBV co-infection, but not HIV infection. Of importance, the most highly significant association was with region of tribal origin; individuals from the upper and northern regions of Ghana were 18.9 (8.4-42.6;p<0.001) and 6.6 (2.4-18.2;p<0.001) more likely to be infected with HCV, compared to individuals from other regions

in Ghana. CONCLUSIONS: These data suggest that several transmission modes, particularly those associated with cultural skin-piercing practices, are likely to be contributing to the current HCV epidemic in Ghana, West Africa, and the distribution of these cultural practices may have led to substantial regional variation in HCV prevalence. Disclosures: The following people have nothing to disclose: Jennifer E. Layden, Richard O. Phillips, Fred S. Sarfo, Dorcas O. Owusu, Nallely Mora, Joseph Forbi, Stephanie Kliethermes, Shirley P. Owusu-Ofori, Ohene Opare-Sem, Kenrad Nelson, Richard Cooper Background HIV/HCV co-infection is very common in the South China mainly caused by intravenous drug using, and poor sustained virological response (SVR) had also been found in HIV/HCV co-infection with the therapy of Interferon plus Rib-avirin in South China.

Although it is possible that these aspects are specifically deranged in the liver, we observed the morphological characteristics of VPA hepatotoxicity in human myoblasts,3 implicating the same mechanism in our in vitro model. Moreover, an elevated serum creatine kinase in patients with VPA toxicity points

to a similar direct toxic effect on skeletal muscle.11 Unlike mature skeletal muscle and brain, the liver can proliferate in response to damage, and there is clear evidence of hepatocyte proliferation in patients with AHS. We have shown that treatment with 2 and 10 mM VPA impairs cellular proliferation in vitro, and that p.Q1236H increases mtDNA mutability in yeast and may decrease mtDNA copy number in myotubes. The yeast system is a proven method to study the effects on mtDNA Gamma-secretase inhibitor of both strong and weak POLG mutations, such as p.E1143G, whose effects are very mild and cannot easily be observed in higher eukaryotes.14 After a limited number of cell divisions most yeast mitochondria are homoplasmic, as the heteroplasmic state is always transient in S. cerevisiae.14 Therefore, conditions that cause increased mtDNA mutability, even at a low extent, lead to an increase of respiratory

deficient cells (i.e., petite mutants) after only a few generations. For the p.Q1236H mutation we observed a small but significant increase ABT-888 in extended mtDNA mutability determined as an increase in petite frequency. Observation of this effect in a yeast model predicts that a similar effect would occur in human cells, resulting in mtDNA copy number reduction, as observed in myotubes harboring this mutation. This raises the possibility that both mechanisms independently compromise the regenerative capacity of the liver, thus inhibiting the endogenous capacity for liver repair in response to an external insult. this website For VPA, this could be through the inhibition of histone deacetylases, which regulate gene expression by relaxing chromatin structure and facilitating access to DNA by the transcriptional

machinery.19 In this study, over 50% (8/14) of patients with probable VPA hepatotoxicity had heterozygous POLG substitutions associated with >20-fold increased risk of VPA-induced liver injury, seven of whom harbored previously described single nucleotide polymorphisms; p.Q1236H and p.E1143G . Here we show that p.Q1236H is not phenotypically neutral, with histidine at position 1236 increasing both mtDNA deletion frequency and point mutability frequency in yeast. However, the phenotype of both substitutions is mild, explaining why these alleles are common throughout the world (p.Q1236H ≤8.6%, and p.E1143G ≤4%). This suggests p.Q1236H and p.E1143G are only disadvantageous in specific contexts, such as exposure to VPA. Screening for functional POLG substitutions will minimize the risk of fulminant liver failure in patients exposed to VPA. Global and Hispanic control data for p.Q1236H was kindly supplied by Dr. Andy Singleton, NIH, Bethesda, MD.

This is the first report of infection in mulberry trees

by HSVd. “
“Commercial parsley plants in Safranbolu were found with symptoms of decline, stunting, yellowing and many galls in the roots, symptoms typical of infestation by root knot nematodes. Morphological, biochemical and molecular methods were used Selleckchem Sirolimus to identify the causal root knot nematode species. Morphological characteristic and perineal patterns of the females and isoenzyme phenotypes matched the description of Meloidogyne arenaria. Polymerase chain reaction with the M. arenaria species-specific Far/Rar primer set also produced a 420-bp fragment, the same as obtained with a positive control population of M. arenaria. Results, therefore, confirm that the root knot nematodes isolated from parsley roots were M. arenaria. This is the first report of M. arenaria infecting parsley in Turkey. “
“Although the tobacco N gene, which confers resistance to Tobacco mosaic virus (TMV), is transcriptionally induced by infection with TMV, the regulatory mechanism has not previously been elucidated. We found that a 5′-flanking region of the N gene

exhibits TMV-inducible promoter activity and that the region from −290 to −271 includes a cis-acting JQ1 solubility dmso element in response to infection. The activity required N protein and signal components of N-mediated resistance. These results suggest that transcription of the N gene is positively regulated by N-mediated resistance signalling. “
“Mallotus japonicus with witches’ broom disease were observed in Jeollabuk-do, Korea. A phytoplasma from the infected leaves was identified, based on the 16S rDNA, 16S-23S intergenic spacer region, and fragment of rp operon and tuf gene sequences. The 16S rDNA sequences exhibited maximum (99.7%) similarity with Iranian lettuce phytoplasma, the rp operon sequences exhibited 100% similarity with Goldenrain stunt phytoplasma, and the tuf gene sequences exhibited 99.8% similarity with Japanese selleck compound spurge yellows phytoplasma. Results of the sequence analysis and phylogenetic studies confirmed that the phytoplasma

associated with M. japonicus in Korea was an isolate of Aster Yellows group (subgroup16SrI-B). “
“Plant viruses can cause serious crop losses. Calcium homoeostasis is involved in the movement of animal viruses. We have examined whether intracellular calcium flux can interfere with spread of virus in plants. The calcium channel blocker verapamil, applied to Nicotiana tabacum cv. Xanthi-nc plant leaves, interfered with Tobacco mosaic virus infection in treated and untreated leaves, reducing TMV lesion number by 68 and 71%, respectively. Verapamil interfered with calcium homoeostasis of leaf cells, evident by increased calcium efflux from leaf segments. This is a first effort to use calcium channel blockers as an inducer of systemic virus resistance in plants.

white) race (OR=1.34, 95% CI: 1.09–1.66), pre-LT diabetes (OR 1.23, 95% CI: 1.08–1.48) or HF (OR 2.21, 95% CI: 1.58–3.09) and discharge to a skilled nursing facility (vs. home) (OR 2.99, 95% CI: 2.63–3.40) after index LT. Findings were consistent for 90d readmissions. Mean length of stay for a CVD-related rehospitalization was 7.0 ± 10.0 days. Thirty-day in-hospital mortality was 0.57% and comorbid CVD conditions were present in 91.7% of these deaths. CONCLUSIONS: Cardiovascular disease is a leading contributor to both 30- and 90-day readmission after LT and is primarily due to non-ischemic

etiologies. This study identifies patients at high risk for readmission after LT with CVD comorbidity that may benefit from medical optimization through a tailored multidisciplinary care SAHA HDAC datasheet pathway prior to discharge. Disclosures: Josh Levitsky – Grant/Research Support: Salix, Novartis; Speaking and Teaching: Gilead, Salix, H 89 Novartis The following people have nothing to disclose: Lisa B. VanWagner, Marina Serper, Raymond Kang, Brittany Lapin, Donald M. Lloyd-Jones, Anton I. Skaro, Samuel Hohmann Background: Whilst non-invasive biomarkers have been shown to accurately predict significant liver fibrosis their ability to provide information on clinical prognosis is less well developed. Aim: To investigate whether non-invasive biomarkers are prognostic factors for clinical outcomes (e.g. all-cause & liver mortality and the development of liver cancer) in patients with chronic

liver disease.

Methods: A systematic review of evidence published between 1st January 2002 and 1st October 2012 identified from Embase, MEDLINE and Pubmed Central was performed using the following terms: ‘encephalopathy,’ ‘death,’ ‘liver transplant,’ ‘mortality,’ selleck chemical ‘ascites,’ ‘cancer,’ ‘variceal’ OR ‘varices’ between 1st January 2002 and 1st October 2012. Studies were included if >1 non-invasive biomarkers (APRI (AST:platelet ratio index), Fib-4, AST:ALT ratio, BARD, NFS, ELF, Hepascore, Fibrotest, Fibrometer, Forns, Fibroscan or transient elastography) were examined in relation to >1 clinical outcomes in the search criteria. Where possible Hazard Ratios (HRs) for each biomarker were extracted and if appropriate, pooled across studies using a random effects model. Results: The search identified 1456 results. After removal of 298 duplicates, 31 unique studies met selection criteria. There was significant study heterogeneity regarding choice of biomarker (and cut-off), disease aetiology, choice of clinical outcome, analysis method and reporting standards. The commonest markers assessed were APRI (13 studies, 7842 patients), Fib-4 (6 studies, 4385 patients) and AST:ALT ratio (6 studies, 1716 patients). Three studies from which HR information for overall survival could be extracted (either directly or from log-rank information) were analyzed. For an APRI cut-off of >1.5–2.0 in patients with viral hepatitis C (HCV) a summary HR for overall mortality of 2.51 (1.37–4.60) and 4.43 (1.64–11.

Importantly, Axl knock-down severely impaired resistance to TGF-β-mediated growth inhibition. Selumetinib molecular weight Analysis of the Axl interactome revealed binding of Axl to 14-3-3ζ, which is essentially required for Axl-mediated cell invasion, transendothelial

migration and resistance against TGF-β. Axl/14-3-3ζ signaling caused phosphorylation of Smad3 linker region (Smad3L) at Ser213, resulting in the upregulation of tumor-progressive TGF-β target genes such as PAI1, MMP9 and Snail as well as augmented TGF-β1 secretion in mesenchymal HCC cells. Accordingly, high Axl expression in HCC patient samples correlated with elevated vessel invasion of HCC cells, higher risk of tumor recurrence after liver transplantation, strong phosphorylation of Smad3L and lower survival. In addition, elevated expression

of both Axl and 14-3-3ζ showed strongly reduced survival of HCC patients. Conclusion: Our data suggest that Axl/14-3-3ζ signaling is central for TGF-β-mediated HCC progression and a promising target for HCC therapy. (Hepatology 2014) “
“Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated Ferrostatin-1 interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, selleckchem and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half

were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ≤3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups. Conclusion: This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response.

Importantly, Axl knock-down severely impaired resistance to TGF-β-mediated growth inhibition. Erlotinib Analysis of the Axl interactome revealed binding of Axl to 14-3-3ζ, which is essentially required for Axl-mediated cell invasion, transendothelial

migration and resistance against TGF-β. Axl/14-3-3ζ signaling caused phosphorylation of Smad3 linker region (Smad3L) at Ser213, resulting in the upregulation of tumor-progressive TGF-β target genes such as PAI1, MMP9 and Snail as well as augmented TGF-β1 secretion in mesenchymal HCC cells. Accordingly, high Axl expression in HCC patient samples correlated with elevated vessel invasion of HCC cells, higher risk of tumor recurrence after liver transplantation, strong phosphorylation of Smad3L and lower survival. In addition, elevated expression

of both Axl and 14-3-3ζ showed strongly reduced survival of HCC patients. Conclusion: Our data suggest that Axl/14-3-3ζ signaling is central for TGF-β-mediated HCC progression and a promising target for HCC therapy. (Hepatology 2014) “
“Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated www.selleckchem.com/products/Vorinostat-saha.html interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, click here and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half

were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ≤3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups. Conclusion: This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response.

Strengthening the probable association between secondhand smoke exposure and the development of CH is the fact that double the http://www.selleckchem.com/products/MDV3100.html number of survey responders developed CH at or before 20 years of age if during their childhood they lived with a parent who smoked cigarettes. “
“Headache is one of the most common complaints presenting to primary care physicians and neurologists. Although the vast majority of headache syndromes are benign, clinicians are faced with the crucial task of differentiating benign headache disorders from potentially life-threatening conditions. Given the broad range of disorders that present with headache, a logical and orderly approach

is necessary to facilitate the prompt diagnosis and treatment of various kinds of head pain. This chapter reviews the key elements of the headache history, general physical and neurological examinations, approach to headache diagnosis, and treatment plan. “
“The Selleck MK-8669 “just world hypothesis” is the belief that a poor outcome to treatment always implies patient noncompliance. However, all disease states have a spectrum of severity, with the

most severe end representing treatment failures despite compliant patients and excellent care. Some refractory headache patients represent this group of compliant patients, who had excellent care but who have bad disease. “
“(Headache 2010;50:141-143) “
“The ideal medication for prevention and treatment of migraine would have no side effects, no risk, would be safe in pregnancy, as well as being highly effective while remaining inexpensive. Of course, no such medication exists, but magnesium comes closer selleck compound than many interventions on all these fronts. Magnesium oxide is frequently used in pill form to prevent migraine, usually at a dose of 400-500 mg per day. Acutely, it can be dosed in pill form at the same dosage, or given intravenously as magnesium sulfate at 1-2 gm. The most frequent side effect is diarrhea, which can be helpful in those prone to constipation. The diarrhea and abdominal cramping that is sometimes experienced is dose responsive, such that a lower dose or decreasing the frequency

of intake usually takes care of the problem. Magnesium oxide in doses up to 400 mg is pregnancy category A, which means it can be used safely in pregnancy. Magnesium sulfate, typically given intravenously, now carries a warning related to bone thinning seen in the developing fetus when used longer than 5-7 days in a row. This was discovered in the context of high doses being given to pregnant women to prevent preterm labor. The strongest evidence for magnesium’s effectiveness is in patients who have, or have had, aura with their migraines. It is believed magnesium may prevent the wave of brain signaling, called cortical spreading depression, which produces the visual and sensory changes that are the common forms of aura.

The sections were washed twice, after all incubation steps, in phosphate-buffered

saline for 5 minutes. Then slides were microwave-oven heated three times for 5 minutes in Tris/ethylenediaminetetra-acetic acid pH 9.0 buffer (heat-induced epitope retrieval), and washed with phosphate-buffered saline. Sections were subsequentially incubated in the presence of the primary antibody overnight at −4°C. The specimens were then incubated with the LSAB HRP detection kit (Universal DakoCytomation PLX3397 price LSAB+ System HRP) at room temperature, according to the manufacturer’s instructions. As a chromogen, 3-amino-9-ethylcarbazole was used for 5 minutes at room temperature with subsequent nuclear counterstaining with hematoxylin. Normal mouse serum was

used instead of primary antibodies as a negative control. A four-grade semiquantitative scoring selleck products system (in other words, score 0-3), performed by one pathologist (C.T.) unaware of other variables, was adopted for the evaluation of CYP2R1 and CYP27A1 immunohistochemical expression. The score was graded according to the intensity of the staining: score 0 was defined as the absence of significant reactivity, scores 1 and 2 as slight and moderate reactivity, respectively, and score 3 as intense reactivity. Because a slight degree of variation could be observed in the immunohistochemical expression of CYP2R1 and CYP27A1 among different areas of the same sample, the most intense reactivity observed in the biopsy specimen was recorded as the summary score. check details Immunohistochemical analysis of CYP450 was performed for control purposes using a specific primary monoclonal antibody (clone 1A2, Abcam, MA) and evaluated by the same four-grade semiquantitative scoring system adopted for CYP27A1 and CYP2R1 assessment. Patients were treated with pegylated interferon α-2a (Pegasys, Roche, Basel, Switzerland) 180 μg /week or pegylated interferon 2b (Peg-Intron, Schering) 1.5 μg/kg/week plus ribavirin

at a dosage of 1000 or 1200 mg/day according to body weight (1000 mg/day for a body weight of <75 kg, 1200 mg/day for a body weight of >75 kg) for 48 weeks. Patients were withdrawn from treatment if they did not achieve a virological response, defined as undetectable serum HCV RNA by polymerase chain reaction, within 24 weeks after start of treatment.24 Sustained virological response (SVR) was defined as negative serum HCV RNA at polymerase chain reaction 6 months after stopping antiviral therapy. Continuous variables were summarized as mean ± standard deviation, and categorical variables as frequency and percentage. The Student t test and analysis of variance were used when appropriate. Multiple linear regression analysis was performed to identify independent predictors of 25(OH)D serum levels as a continuous dependent variable.

Hypothyroidism was defined as having a previous diagnosis of the disease and receiving LT4 replacement,

or newly diagnosed patients with hypothyroidism according to TSH and free T4 levels during the initial screening. Results: CHIR 99021 Patients were divided according to the presence (n=209) or absence (n=44) of NAFLD by MRS. Patients with a fatty liver showed a worse metabolic profile with higher BMI, more frequent T2DM and more severe insulin resistance. They also had a higher prevalence of hypothyroidism (18 [6.7%] vs. 0 [0%], p<0.05). When patients with biopsy-proven NAFLD were divided into those with and those without NASH, no difference in the prevalence of hypothyroidism was observed (14 [10.3%] vs. 2 [4.3%], p=0.37). After excluding patients on levothyroxine replacement, plasma TSH and free T4 levels were similar between patients with and without NAFLD, and those with and without NASH. Patients were also divided into those with and without hypothyroidism to assess if it had any impact in the development of NAFLD or NASH. Patients with hypothyroidism showed a similar amount of liver

fat (21±2% vs. 20±1%, p=0.79), NAFLD activity this website score (NAS) (3.8±0.3 vs. 4.0±0.1, p=0.74) and liver fibrosis (0.8±0.3 vs. 0.8±0.1, p=0.92). Finally, TSH and free T4 plasma levels were not correlated to insulin sensitivity, liver fat by MRS or the severity of histological damage. Conclusions: We found a slight increase in the prevalence of hypothyroidism in patients with NAFLD. However, in this cohort of middle-aged predominantly obese patients we did not find any suggestion that hypothyroidism (or a TSH elevation within the normal range)

worsens liver disease (NAS or fibrosis) see more in patients with NASH. This suggests that the association of hypothyroidism with NAFLD may be more closely linked to obesity and the associated metabolic abnormalities that lead to steatosis rather than the severity of liver disease. Disclosures: Beverly Orsak – Employment: UTHSCSA Kenneth Cusi – Consulting: Merck, Daichi-Sankyo, Roche, Janssen; Grant/Research Support: Takeda, Novartis, Mannkind The following people have nothing to disclose: Fernando Bril, Romina Lomonaco, Sreevidya Subbarayan, Sushma Kadiyala, Carolina Ortiz-Lopez, Amy Webb Background and Aim: The true role of vitamin D deficiency in the development of non-alcoholic fatty liver (NAFLD) and steatohepatitis (NASH) remains poorly understood. Previous studies have been overall small, retrospective or relied on surrogate markers for the diagnosis of NAFLD and NASH. We aimed to assess the relationship between vitamin D deficiency and NAFLD. Methods: We recruited 235 patients (52±1 years, 67% male, 33.4±0.