3% for sensitivity and 7.7% for the positive predictive value). For the total steatosis grade between preoperative Sotrastaurin right biopsy versus intraoperative right and left biopsies, moderate agreement was seen as reflected by weighted kappa values of 0.44 and 0.40. The weighted kappa value between intraoperative right and left biopsies was 0.77, and thus indicating substantial agreement. Similar results were noted in macrovesicular and microvesicular steatosis subtypes. Multivariate analysis indicated that independent factors affecting the sampling variability of the total steatosis in preoperative and intraoperative biopsies, included greater systolic blood pressure (odds

ratio [OR], 1.01), body mass index (OR, 1.08) and serum alanine aminotransferase (OR,

1.02), and less high-density lipoprotein this website cholesterol (OR, 0.98; P <0.05 for all). Conclusions: Our data suggest that radiological studies were considerably limited for detecting donor hepatic steatosis in LDLT and that further substantial sampling variability exists between preoperative and intraoperative liver biopsies, according to the clinical and metabolic parameters. Therefore, preoperative and selective intraoperative liver biopsies should be performed to assess donor steatosis in LDLT. Disclosures: Han Chu Lee - Grant/Research Support: Medigen Biotechnology Co., Novartis, Roche, Bayer HealthCare, Bristol-Myers Squibb, INC research, Boehringer Ingelheim, Taiho Pharmaceutical Co., Yuhan Co. The following people have nothing to disclose: Mi-Jung Jun, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Dong Jin Suh Several noninvasive scoring systems had been developed in patients with NAFLD aimed at distinguishing between those with and without advanced liver fibrosis. They are the NAFLD fibrosis score (NFS), the aspartate aminotransferase (AST)/platelet ratio

index (APRI), the FIB-4 score, the NIKEI score, and the BARD score. Validation studies, however, had included small number of patients and most came from single centers. The AIM of our study was to perform a large, independent validation of those scoring systems. METHODS: A total of 672 patients with those NAFLD were included. Patients came from several institutions around the world and none of these patients had been included in the original prior studies that created the scoring systems. Fibrosis was staged on the scale 0 to 4 proposed by Kleiner et al. with stage 3 and 4 meaning adavnced fibrosis. The five scores mentioned above were calculated using the original published formulas. The same two cut-points described in the original publications were used to group patients; they were −1.455 and 0.676 for the NAFLD-FS; 0.5 and 1.5 for the APRI; 1.30 and 2.67 for the FIB-4; and 0. 。535 and 0.2294 for the NIKEI score. For the BARD score, a value >2 was used.

A new glucocorticosteroids, with the same efficacy as traditional ones, but with more favourable safety profile was developed. Aim of this study has been to define the efficacy and safety

of oral beclomethasone dipropionate (BDP) compared to 5-ASA enema in left-sided active UC. Methods: In an eight-week, investigator blind comparative study, patients with left-sided mild-moderately active UC were randomized to receive oral 5-ASA (2.4 g/day) plus oral BDP (10 mg/day) or 5-ASA enema (4 g/day). Efficacy was evaluated by the Disease Activity click here Index (DAI). Safety was evaluated by monitoring adverse events, haematochemical parameters and adrenal function. Results: Sixty-two outpatients were enrolled and randomly treated with BDP (n = 30) or 5-ASA enema (n = 32). Complete remission was achieved in 42.9% of BDP patients Ensartinib vs 63.6% of 5-ASA, a difference not statistically significant. Reduction of mean plasma cortisol was observed in BDP group. Mild signs of hypothalamic-pituitary-adrenal

axis suppression were observed in four patients of BDP group. Conclusion: Oral BDP gave an overall treatment result in patients with left-sided active UC with few signs of systemic side-effects, so it can be considered, a useful therapeutic regimen in patients non compliant to 5-ASA enema. Key Word(s): 1. ULCERATIVE COLITIS; 2. BECLOMETHASONE; 3.5-ASA; Presenting Author: JA YOUNG JUNG Additional Authors: JI WON KIM, BYEONG GWAN KIM, KOOK LAE LEE Corresponding Author: JA YOUNG JUNG Affiliations: Seoul National University Boramae Medical Center Objective: There is evidence that inflammatory bowel disease (IBD) correlates with human metabolism and chronic inflammation. This study was focused on the correlation of disease activity between enzyme-linked immnosorbent assays (ELISA) values and quantitative

reverse transcription polymerase chain reaction (qRT-PCR) values of Palmatine ghrelin, obestatin, obestatin/Ghrelin ratio and C-reactive protein in patients with ulcerative colitis (UC). Methods: Level of ghrelin, obestatin and obestatin/Ghrelin ratio were measured in all UC patients. UC patients of 21 using ELISA classified as 12 with active disease and 9 with remission of disease. UC patients of 35 using qRT-PCR classified as 18 with active disease and 17 with remission of disease. Disease activity in all UC patients was evaluated with the Mayo score and active UC was defined as a Mayo score of more than 2. C-reative protein was measured as marker of inflammation.

Significantly fewer Ki67- and pH3-positive hepatocytes MAPK inhibitor were detectable in Mdr2-/-c-MycΔ/Δ mice and regain of liver weight was significantly delayed. Similarly, Mdr2-/-c-MycΔ/Δ hepato-cytes transplanted into Fah-/—mice failed to repopulate the livers compared to c-Myc WT hepatocyte. Mechanistically, we provide evidence that c-Myc is required to maintain metabolic homeostasis in hepatocytes during chronic liver injury. Mechanistically, we provide evidence that loss of c-Myc significantly impaired oxidative phosphorylation in isolated hepatocytes. Accordingly, ATP levels were significantly

lower in Mdr2-/-c-MycΔ/Δ hepatocytes and the ATP/ADP ratio increased in Mdr2-/-c-MycΔ/Δ. Gene expression analysis identified several networks that were regulated by c-Myc including cellular assembly/organization, growth/proliferation GDC-0449 datasheet and inflammatory response. Together, we provide evidence that c-Myc is a central regulator of liver homeostasis in mice with chronic liver injury in contrast to the only modest phenotype of WT mice with a deletion of c-Myc in liver. C-Myc is specifically required to prevent

liver injury and induce liver regeneration in mice with pre-existing chronic liver injury. Disclosures: Michael P. Manns – Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Idenix, Achillion, GSK, Merck/MSD, Janssen, Medgenics; Grant/ Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis The following people have nothing to disclose: Stephanie Klett, Kristin Hanak, Bruno Guigas, Robert Geffers, Jessica Endig, Laura E. Buitrago, Silke Marhenke, Arndt Vogel Background: TIGAR is a bisphosphatase that has been linked to the inhibition of glycolysis and increased carbohydrate flux through the pentose-phosphate shunt (PPS). A PPS intermediate, xylulose-5-phosphate (X5P) has

been shown to suppress AKT phosphorylation by activating protein phosphatase 2A (PP2A). Increased AKT phosphorylation has been demonstrated to be an important determinant of sorafenib resistance in hepato-cellular carcinoma (HCC) cells. Hypothesis: Overexpression of TIGAR may improve chemosensitivity in sorafenib-resistant ALOX15 HCC cells by inhibiting glycolysis, and promoting the formation of X5P that subsequently leads to diminished AKT phos-phorylation via PP2A activation. Methods: HepG2, Hep3B, FOCUS and HepaRG HCC cell lines were employed in this study to assess the correlation between AKT phosphorylation and TIGAR expression/chemosensitivity. Full-length human TIGAR cDNA was overexpressed in cells with low endogenous TIGAR levels (HepaRG and FOCUS). Overexpression was confirmed by real-time PCR, Western-blotting, subcellular localization studies, and biochemical assays. Cellular X5P content was assessed by HPLC-MS/MS. AKT phosphorylation was measured by Western-blotting.

) There is a lack of data showing an effect of omega-3 fatty acids in nonalcoholic steatohepatitis. The combination of eicosapentaenoic acid and docosahexaenoic acid is an approved treatment of hypertriglyceridemia. Scorletti et al. randomized 103 patients with nonalcoholic fatty liver disease to the combination or placebo. Steatosis was assessed by magnetic resonance spectroscopy, rather than histologically. The combination failed to significantly improve steatosis, but interestingly, several patients in the placebo arm showed enrichment in erythrocyte omega-3. After correcting for this unexpected confounding

factor, the investigators detected an improvement of steatosis. This trial highlights Pirfenidone in vivo the importance of measuring exposure to intervention drug not only to evaluate compliance, but also to assess exposure in the control arm. (Hepatology 2014;60:1211-1221.) Despite its peculiar features, the

molecular pathophysiology of primary biliary cirrhosis (PBC) remains to be understood. Recent genome-wide association studies (GWASs) proposed pathways involving immunological and apoptotic genes. Lleo et al. Palbociclib in vitro also chose an unbiased, discovery approach, but with a completely different perspective. The investigators performed a detailed analysis of the proteome of apoptotic bodies from human intrahepatic biliary epithelial cells. They identified proteins specifically expressed or specifically missing in these apoptotic bodies. The data point to innate immune system and inflammatory response. It will be interesting to see how the identified proteins can be mechanistically implicated in the development of PBC. (Hepatology 2014;60:1314-1323.) Remote ischemic preconditioning consists of mechanically interrupting the blood flow to a limb repeatedly to induce cycles of local ischemia. This remote stress induces a systemic response that protects various organs against ischemia reperfusion (I/R). In a series of elegant experiments, Oberkofler et al. demonstrate that remote ischemic preconditioning activates platelets, which release serotonin, to stimulate VEGF secretion. These

factors induce expression of the protective matrix metalloproteinase-8 and interleukin-10 in the liver and protect it against I/R injury. The investigators went on to show that this Bay 11-7085 effect also applies to other organs and other insults. They conclude that platelet response to local stress primes the body against impending injury. (Hepatology 2014;60:1409-1417.) “
“We read the article by Sersté and colleagues1 with great interest. The authors carried out a single-center, observational, prospective study and evaluated the effects of nonselective beta-blockers (NSBBs) on the survival of 151 patients with cirrhosis and refractory ascites. Seventy-seven patients (51%) received propranolol (113 ± 46 mg/day) for the prevention of gastrointestinal bleeding.

[2] To confirm and extend this observation we investigated STAT3 activation in the presence of HCV replication in the context of a HCV genomic replicon and the complete HCV life cycle (JFH-1). STAT3 activation requires posttranslational modifications

through phosphorylation at tyrosine 705 (Y705) to be functionally active. Phosphorylation at this Y705 residue results in STAT3 dimerization and translocation to the nucleus. In the presence of both the genomic replicon (Fig. 1A) and JFH-1 infection (Fig. 1B), levels http://www.selleckchem.com/products/idasanutlin-rg-7388.html of STAT3-Y705 phosphorylation were significantly increased in the presence of HCV, in comparison to uninfected Huh-7 cells, as shown by specific detection of STAT3-Y705 by immunoblot and quantification by densitometry analysis. The presence of replicating HCV

did not seem to alter total STAT3 protein within Huh-7 cells, suggesting that HCV replication does not significantly impact basal STAT3 expression (Fig. 1A,B). We next sought to determine if this HCV-dependent increase in STAT3-Y705 phosphorylation corresponded to a concomitant increase in functional STAT3 transcriptional activity. Huh-7.5 cells infected with HCV JFH-1 (48 hours) and HCV genomic replicon cells were transiently transfected with a plasmid containing a STAT3-responsive DNA element driving luciferase (pSTAT3-luc). Luciferase results were expressed as a fold change relative to the control cells (no HCV Fossariinae replication). HCV genomic replicon (Fig. 1C) and JFH-1 (Fig. 1D) replication significantly enhanced STAT3 see more luciferase output. This indicates that HCV replication induces activation of STAT3 by way of increased STAT3-Y705 phosphorylation, correlating with enhanced STAT3 transcriptional activation.

Collectively, these results demonstrate that HCV replication drives activation of functional STAT3. To investigate if STAT3 activation affects the HCV life cycle, we expressed a constitutively active STAT3 molecule (PRc/CMV-STAT3-C) in Huh-7 cells harboring HCV replication. STAT3-C is a constitutively active form of STAT3 in which two cysteine residues inserted into the C-terminal loop of STAT3 allows for the formation of disulfide bonds between STAT3 monomers resulting in the formation of active STAT3 homodimers.[17] Transient expression of STAT3-C (48 hours) resulted in a significant increase in STAT3-dependent luciferase output, indicating that this construct is functional and active in our system (Supporting Fig. 1). We then sought to express STAT3-C both transiently and stably in the context of JFH-1 infection. Transient expression of STAT3-C, followed by infection with JFH-1 (MOI = 0.01) for 24 hours resulted in a significant 2-fold increase in HCV replication (Fig. 2A). These results were then substantiated using Huh-7.5 cells stably expressing STAT3-C (Fig. 2B).

13 In contrast to those studies, we did not observe a decrease in α-SMA-positive MFBs in cyclopamine-treated tumors (data not shown). Moreover, the importance of Hh signaling in cancer cells, as opposed to stromal cells, has recently been

emphasized.41 Our observations are most consistent with a direct effect of cyclopamine on tumor cells in vivo, although we cannot exclude a noncytotoxic effect of cyclopamine on MFB function. In conclusion, MFB-derived PDGF-BB protects CCA cells from TRAIL-induced apoptosis. This cytoprotection is exerted through a coactivation network involving Hh signaling. These observations support the examination of selective Hh inhibitors (currently in clinical development42, 43) in human CCA. The Affymetrix click here U133 Plus 2.0 GeneChip

analysis was performed in collaboration with the Genomics Technology Center Core and Dr. Y. Li from the Division of Biomedical Statistics and Informatics (both Mayo Clinic, Rochester, MN). The assistance of Dr. U. Yaqoob with the immunoblotting for (phospho-)PDGFR-β is also gratefully acknowledged, as well as the superb secretarial service Proteasome inhibition of C. Riddle. Additional Supporting Information may be found in the online version of this article. “
“Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall

catchment population of 700,000 people. Gender-matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long-term outcomes of all three groups, and compared selleck kinase inhibitor T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver-related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts—when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension.

Hepatic metastases have variable appearances depending on the primary tumor and are characterized Selleckchem ABT-199 as hypervascular or hypovascular, enhancing more or less than surrounding parenchyma (Fig. 7). Hypervascular metastases are seen with neuroendocrine tumors, renal cell carcinoma, thyroid carcinoma, melanoma, and sarcoma. Metastases from other primaries tend to be hypovascular. Internal hemorrhage may occur with metastases from renal cell carcinoma, melanoma, and lung cancer, often demonstrating

T1 hyperintensity (Fig. 8). Hepatobiliary imaging with Eovist and DWI can be useful for detection of small hepatic metastases, demonstrating improved sensitivity over traditional MRI and CT.17-22, 85, 86 MRI is a highly specific and accurate modality for FLL characterization. An experienced MR radiologist is essential to maintain high-quality Selumetinib mw liver MR protocols, determine appropriate indications for hepatocyte versus extracellular contrast agents, and guide management. Although many hepatic lesions have characteristic imaging features, consideration of the clinical context, in particular the presence or absence of underlying liver disease when considering

HCC or ICC, is essential to confidently diagnose and direct management in these patients. “
“During liver development and regeneration, hepatocytes undergo rapid cell division and face an increased risk of DNA damage associated with active DNA replication. The mechanism that protects proliferating hepatocytes from replication-induced DNA damage remains unclear. Nucleostemin (NS) is known to be up-regulated during liver regeneration, and loss of NS is associated with increased DNA damage in cancer cells. To determine whether NS is involved in protecting the genome integrity of proliferating hepatocytes, we created an albumin promoter-driven NS conditional-null (albNScko) mouse model. Livers of albNScko mice begin to show loss of NS in developing Liothyronine Sodium hepatocytes from the first postnatal week and increased DNA damage and hepatocellular injury at 1-2 weeks of age. At 3-4 weeks, albNScko

livers develop bile duct hyperplasia and show increased apoptotic cells, necrosis, regenerative nodules, and evidence suggestive of hepatic stem/progenitor cell activation. CCl4 treatment enhances degeneration and DNA damage in NS-deleted hepatocytes and increases biliary hyperplasia and A6+ cells in albNScko livers. After 70% partial hepatectomy, albNScko livers show increased DNA damage in parallel with a blunted and prolonged regenerative response. The DNA damage in NS-depleted hepatocytes is explained by the impaired recruitment of a core DNA repair enzyme, RAD51, to replication-induced DNA damage foci. Conclusion: This work reveals a novel genome-protective role of NS in developing and regenerating hepatocytes.

Hepatic metastases have variable appearances depending on the primary tumor and are characterized MAPK inhibitor as hypervascular or hypovascular, enhancing more or less than surrounding parenchyma (Fig. 7). Hypervascular metastases are seen with neuroendocrine tumors, renal cell carcinoma, thyroid carcinoma, melanoma, and sarcoma. Metastases from other primaries tend to be hypovascular. Internal hemorrhage may occur with metastases from renal cell carcinoma, melanoma, and lung cancer, often demonstrating

T1 hyperintensity (Fig. 8). Hepatobiliary imaging with Eovist and DWI can be useful for detection of small hepatic metastases, demonstrating improved sensitivity over traditional MRI and CT.17-22, 85, 86 MRI is a highly specific and accurate modality for FLL characterization. An experienced MR radiologist is essential to maintain high-quality find more liver MR protocols, determine appropriate indications for hepatocyte versus extracellular contrast agents, and guide management. Although many hepatic lesions have characteristic imaging features, consideration of the clinical context, in particular the presence or absence of underlying liver disease when considering

HCC or ICC, is essential to confidently diagnose and direct management in these patients. “
“During liver development and regeneration, hepatocytes undergo rapid cell division and face an increased risk of DNA damage associated with active DNA replication. The mechanism that protects proliferating hepatocytes from replication-induced DNA damage remains unclear. Nucleostemin (NS) is known to be up-regulated during liver regeneration, and loss of NS is associated with increased DNA damage in cancer cells. To determine whether NS is involved in protecting the genome integrity of proliferating hepatocytes, we created an albumin promoter-driven NS conditional-null (albNScko) mouse model. Livers of albNScko mice begin to show loss of NS in developing RG7420 mouse hepatocytes from the first postnatal week and increased DNA damage and hepatocellular injury at 1-2 weeks of age. At 3-4 weeks, albNScko

livers develop bile duct hyperplasia and show increased apoptotic cells, necrosis, regenerative nodules, and evidence suggestive of hepatic stem/progenitor cell activation. CCl4 treatment enhances degeneration and DNA damage in NS-deleted hepatocytes and increases biliary hyperplasia and A6+ cells in albNScko livers. After 70% partial hepatectomy, albNScko livers show increased DNA damage in parallel with a blunted and prolonged regenerative response. The DNA damage in NS-depleted hepatocytes is explained by the impaired recruitment of a core DNA repair enzyme, RAD51, to replication-induced DNA damage foci. Conclusion: This work reveals a novel genome-protective role of NS in developing and regenerating hepatocytes.

Culture medium virion DNA was quantified by Real-time PCR assay. Results: E77K/R, D78K/R mutations fully abolished the capsid formation, viral pregenomic RNA encapsidation and DNA replication, while E77K/A, D78K/A mutations formed large aggregates with discount function still supporting replication. In addition, E77K/R, D78K/R core protein mutants were able to interact with wild type HBV core protein monomers, induced irregular core protein aggregates formation and block the correct capsid assembly, HBV replication http://www.selleckchem.com/HSP-90.html and progeny virus production were also inhibited. Conclusions: HBV core protein acidic amimo acids E77K, D78 were critical

for HBV core protein interplay and capsid formation. Changing the charge round the region disrupts core protein assembly and function. Our work provides a new angle and framework GSK 3 inhibitor for further exploring the novel antiviral

strategy. Disclosures: Lai Wei – Advisory Committees or Review Panels: Gilead, AbbVie; Consulting: Gilead; Grant/Research Support: BMS, Roche, Novartis The following people have nothing to disclose: Kai Deng, Dong Jiang Background: Chronic hepatitis B virus (HBV) infection causes liver cirrhosis and hepatocellular carcinoma. Host autoimmune reactions against the virus and infected cells as well as direct cytotoxic effects of viral components contribute to liver injury. The accumulation of the large HBV surface protein (LHBs) in the endoplasmic reticulum (ER) of hepatocytes leads to ER stress. Severely affected cells finally undergo apoptosis or

transform into tumor cells. In this work we show that cytokeratins (CK) are responsible for the intracellular distribution of LHBs. Methods: DNA sequences of LHBs and the small surface protein of HBV (SHBs) were cloned separately into lentiviral vectors. The human hepatoma cell line Huh7 and the untransformed mouse fibroblast cell line NIH3T3 were stably transduced using these vectors. HBs expressing cells were treated with the phospha-tase inhibitor okadaic acid (Oka) and the microtubule (MT) and microfilament (MF) disrupting substances nocodazole and cytochalasin D, respectively. Furthermore immunofluorescence staining, confocal microscopy, proximity ligation assay (PLA) either and surface-plasmon resonance (SPR) were performed. We also analysed the effects of Oka on HBsAg secretion in a separate HBV infection and secretion experiment on primary hepatocytes from Tupaia belangeri (PTHs). Results: Whereas the accumulation of SHBs in both cell lines was finely distributed within the cells, the expression of LHBs in NIH3T3 led to formation of large intracellular aggregates of LHBs protein. In contrast, LHBs was finely distributed within Huh7. Treatment with Oka caused a breakdown of the LHBs together with the CK filament network followed by formation of perinuclear aggregates of CK8/18 together with LHBs.

Identification of molecular mechanisms

of the crosstalk between innate immune responses and nuclear hormone receptor-regulated metabolism can provide insight into the biological consequences of various drug treatments http://www.selleckchem.com/screening/epigenetics-compound-library.html during viral infections, allowing for safer and more accurate assessment of proper drug therapy. We thank Dr. Peter Edwards for reviewing the article. Additional Supporting Information may be found in the online version of this article. “
“The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 ± 1, body mass index = 34.1 ± 0.3 kg/m2) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IRi = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IRi quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured

as an index derived from endogenous glucose LY2835219 research buy production x FPI C59 (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[3H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic

insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). Conclusion: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. (HEPATOLOGY 2012) Insulin resistance (IR) plays a key role in the development of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). Previous studies have reported that patients with NAFLD are insulin resistant at the level of the liver and muscle.