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Nonalcoholic steatohepatitis

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https://www.readbyqxmd.com/read/29666185/hepatocyte-nuclear-receptor-shp-suppresses-inflammation-and-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#1
An Zou, Nancy Magee, Fengyan Deng, Sarah Lehn, Cuncong Zhong, Yuxia Zhang
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide, ranging from nonalcoholic fatty liver (NAFL, steatosis without hepatocellular injury) to the more aggressive nonalcoholic steatohepatitis (NASH, steatosis with ballooning, inflammation, or fibrosis). Although many studies have greatly contributed to the elucidation of NAFLD pathogenesis, the disease progression from NAFL to NASH still remains incompletely understood. Nuclear receptor small heterodimer partner (Nr0b2, SHP) is a transcriptional regulator critical for the regulation of bile acid, glucose, and lipid metabolism...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29662288/nonalcoholic-fatty-liver-disease-and-liver-transplantation-where-do-we-stand
#2
REVIEW
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT...
April 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29661561/clinically-actionable-hypercholesterolemia-and-hypertriglyceridemia-in-children-with-nonalcoholic-fatty-liver-disease
#3
Kathryn E Harlow, Jonathan A Africa, Alan Wells, Patricia H Belt, Cynthia A Behling, Ajay K Jain, Jean P Molleston, Kimberly P Newton, Philip Rosenthal, Miriam B Vos, Stavra A Xanthakos, Joel E Lavine, Jeffrey B Schwimmer
OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network...
April 13, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29661431/stratifying-mortality-in-a-model-for-end-stage-liver-disease-waiting-list-a-brazilian-single-center-study
#4
R B Martino, D R Waisberg, A P M Dias, V B S Inoue, R M Arantes, L B P Haddad, W Andraus, L D Lopes, F H F Galvão, A T W Song, L A C D'Albuquerque
BACKGROUND: The Model for End-Stage Liver Disease (MELD) system reliably predicts mortality in cirrhotic patients. However, the etiology of liver disease and presence of portal vein thrombosis are not directly taken into account in MELD score. Its impact on the outcomes of patients on the waiting list is still unclear. The aim of this study was to investigate mortality and access to transplantation regarding etiology of liver disease and portal vein thrombosis (PVT). METHODS: A total of 465 adult patients on the liver waiting list from August 2015 to August 2016 were followed up until August 2017...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29656147/liver-fibrosis-direct-antifibrotic-agents-and-targeted-therapies
#5
REVIEW
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29653253/cholesterol-and-bile-acid-mediated-regulation-of-autophagy-in-fatty-liver-diseases-and-atherosclerosis
#6
REVIEW
Yifeng Wang, Wen-Xing Ding, Tiangang Li
Liver is the major organ that regulates whole body cholesterol metabolism. Disrupted hepatic cholesterol homeostasis contributes to the pathogenesis of nonalcoholic steatohepatitis, dyslipidemia, atherosclerosis, and cardiovascular diseases. Hepatic bile acid synthesis is the major catabolic mechanism for cholesterol elimination from the body. Furthermore, bile acids are signaling molecules that regulate liver metabolism and inflammation. Autophagy is a highly-conserved lysosomal degradation mechanism, which plays an essential role in maintaining cellular integrity and energy homeostasis...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29651702/tsumura-suzuki-obese-diabetic-mice-derived-hepatic-tumors-closely-resemble-human-hepatocellular-carcinomas-in-metabolism-related-genes-expression-and-bile-acid-accumulation
#7
Tetsuyuki Takahashi, Ulrich Deuschle, Shu Taira, Takeshi Nishida, Makoto Fujimoto, Takao Hijikata, Koichi Tsuneyama
BACKGROUND AND AIMS: Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors...
April 12, 2018: Hepatology International
https://www.readbyqxmd.com/read/29643297/investigation-of-pharmacological-responses-to-anti-diabetic-drugs-in-female-spontaneously-diabetic-torii-sdt-fatty-rats-a-new-nonalcoholic-steatohepatitis-nash-model
#8
Yasufumi Toriniwa, Tomoyuki Saito, Katsuhiro Miyajima, Yukihito Ishii, Kinuko Uno, Tatsuya Maekawa, Tohru Matsui, Shinichi Kume, Takahisa Yamada, Takeshi Ohta
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks...
April 10, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29629906/low-rates-of-retention-into-hepatocellular-carcinoma-hcc-surveillance-program-after-initial-hcc-screening
#9
Ann Robinson, Hesam Tavakoli, Ramsey Cheung, Benny Liu, Taft Bhuket, Robert J Wong
GOALS: To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients. BACKGROUND: Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening. METHODS: We retrospectively evaluated all consecutive adults with cirrhosis from 2014 to 2017 at a single underserved safety net hospital system to determine rates of HCC surveillance at 6 months and at 1 year beyond initial screening...
April 6, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29624631/temporal-trends-in-disease-presentation-and-survival-of-patients-with-hepatocellular-carcinoma-a-real-world-experience-from-1998-to-2015
#10
Nathan G Kim, Pauline P Nguyen, Hansen Dang, Radhika Kumari, Gabriel Garcia, Carlos O Esquivel, Mindie H Nguyen
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015. METHODS: Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015)...
April 6, 2018: Cancer
https://www.readbyqxmd.com/read/29619419/tumor-necrosis-factor-%C3%AE-mediated-hepatocyte-apoptosis-stimulates-fibrosis-in-the-steatotic-liver-in-mice
#11
Yosuke Osawa, Ekumi Kojika, Yukiko Hayashi, Masamichi Kimura, Koji Nishikawa, Sachiyo Yoshio, Hiroyoshi Doi, Tatsuya Kanto, Kiminori Kimura
Hepatocyte apoptosis has been implicated in the progression of nonalcoholic steatohepatitis. However, it is unclear whether the induction of tumor necrosis factor (TNF)-α-mediated hepatocyte apoptosis in the simple fatty liver triggers liver fibrosis. To address this question, high-fat diet-fed mice were repeatedly administered D-galactosamine, which increases the sensitivity of hepatocytes to TNF-α-mediated apoptosis. In mice treated with a high-fat diet plus D-galactosamine, hepatocyte apoptosis and liver fibrosis were induced, whereas both apoptosis and fibrosis were inhibited in these mice following gut sterilization with antimicrobials or knockout of TNF-α...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619418/the-role-of-intestinal-c-type-regenerating-islet-derived-3-lectins-for-nonalcoholic-steatohepatitis
#12
Sena Bluemel, Lirui Wang, Cameron Martino, Suhan Lee, Yanhan Wang, Brandon Williams, Angela Horvath, Vanessa Stadlbauer, Karsten Zengler, Bernd Schnabl
C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells ( Reg3g Tg)...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29615042/higher-non-hdl-cholesterol-to-hdl-cholesterol-ratio-linked-with-increased-nonalcoholic-steatohepatitis
#13
Dianhui Wang, Ling Wang, Zhanqing Wang, Shihong Chen, Yihong Ni, Dongqing Jiang
BACKGROUND: Non-HDL-cholesterol to HDL-cholesterol (non-HDL-c/HDL-c) ratio is a feasible predictor for coronary heart disease, metabolic syndrome, and insulin resistance. Patients with nonalcoholic steatohepatitis (NASH) have an increased risk of developing cardiovascular problems and type 2 diabetes. However, the predictive role of non-HDL-c/HDL-c ratio in NASH hasn't been investigated yet. METHODS: We conducted a retrospective cohort study. A total of 3489 eligible subjects were selected in the present study...
April 3, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29614799/folate-and-b12-levels-correlate-with-histological-severity-in-nash-patients
#14
Mahmud Mahamid, Naim Mahroum, Nicola Luigi Bragazzi, Kasem Shalaata, Yarden Yavne, Mohammad Adawi, Howard Amital, Abdulla Watad
BACKGROUND: The correlation between abnormal vitamin serum levels and chronic liver disease has been previously described in literature. However, the association between the severity of folate serum levels (B9), vitamin B12 and nonalcoholic steatohepatitis (NASH) has not been widely evaluated. Therefore, the aim of this study was to investigate the existence of such a correlation in a cohort of NASH patients. METHODS: All patients aged 18 years and older who were diagnosed with biopsy-proven NASH at the EMMS hospital in Nazareth during the years 2015-2017 were enrolled in this study...
April 2, 2018: Nutrients
https://www.readbyqxmd.com/read/29607946/clinical-characteristics-phenotype-of-lipodystrophy-and-a-genetic-analysis-of-six-diabetic-japanese-women-with-familial-partial-lipodystrophy-in-a-diabetic-outpatient-clinic
#15
Masanori Iwanishi, Jun Ito-Kobayashi, Miki Washiyama, Toru Kusakabe, Ken Ebihara
Objective Our aim was to examine the clinical characteristics and phenotype of lipodystrophy of six diabetic Japanese women with partial lipodystrophy (PL) who received a genetic analysis at a diabetic outpatient clinic. Methods We screened for PL using dual energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) among patients who had a reduced peripheral skinfold thickness at the diabetic outpatient clinic of Kusatsu General Hospital between August 2003 and August 2013. We performed a mutation analysis of candidate genes, including LMNA and PPARG, in two patients with PL and whole-exome sequencing in four patients with PL...
March 30, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29602794/specific-hepatic-sphingolipids-relate-to-insulin-resistance-oxidative-stress-and-inflammation-in-nonalcoholic-steatohepatitis
#16
Maria Apostolopoulou, Ruth Gordillo, Chrysi Koliaki, Sofia Gancheva, Tomas Jelenik, Elisabetta De Filippo, Christian Herder, Daniel Markgraf, Frank Jankowiak, Irene Esposito, Matthias Schlensak, Philipp E Scherer, Michael Roden
OBJECTIVE: Insulin resistance and nonalcoholic fatty liver (NAFL) disease have been linked to several lipid metabolites in animals, but their role in humans remains unclear. This study examined the relationship of sphingolipids with hepatic and peripheral metabolism in 21 insulin-resistant obese patients without (NAFL-) or with (NAFL+) and nonalcoholic steatohepatitis (NASH), and 7 healthy lean individuals undergoing tissue biopsies during bariatric or elective abdominal surgery. RESEARCH DESIGN AND METHODS: Hyperinsulinemic-euglycemic clamps with d-[6,6-2 H2 ]glucose were performed to quantify tissue-specific insulin sensitivity...
March 30, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29599925/a-porcine-placental-extract-prevents-steatohepatitis-by-suppressing-activation-of-macrophages-and-stellate-cells-in-mice
#17
Liang Xu, Naoto Nagata, Mayumi Nagashimada, Fen Zhuge, Yinhua Ni, Guanliang Chen, Junzo Kamei, Hiroki Ishikawa, Yasuhiko Komatsu, Shuichi Kaneko, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29593846/new-insights-into-nod-like-receptors-nlrs-in-liver-diseases
#18
REVIEW
Tao Xu, Yan Du, Xiu-Bin Fang, Hao Chen, Dan-Dan Zhou, Yang Wang, Lei Zhang
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Nod-like receptors (NLRs) are intracellular innate immune sensors of microbes and danger signals that control multiple aspects of inflammatory responses. Recent studies demonstrated that NLRs are expressed and activated in innate immune cells as well as in parenchymal cells in the liver. For example, NLRP3 signaling is involved in liver ischemia-reperfusion (I/R) injury and silencing of NLRP3 can protect the liver from I/R injury...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29578593/high-frequency-of-the-pnpla3-rs738409-g-single-nucleotide-polymorphism-in-hmong-individuals-as-a-potential-basis-for-a-predisposition-to-chronic-liver-disease
#19
Clifford G Tepper, Julie H T Dang, Susan L Stewart, Dao M Fang, Kimberly A Wong, Stephenie Y Liu, Ryan R Davis, Doan Y Dao, Jeffrey P Gregg, Natalie J Török, Moon S Chen
BACKGROUND: An exploratory study was performed to determine the prevalence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs78409 [G] allele among the Hmong as a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic liver disease and is expected to replace viral hepatitis as the leading cause of cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all populations in California, the Hmong experience the highest risk of death from HCC and the highest prevalence of metabolic syndrome risk factors among Asians that predispose them to NAFLD...
April 1, 2018: Cancer
https://www.readbyqxmd.com/read/29577364/screening-for-therapeutic-trials-and-treatment-indication-in-clinical-practice-mack-3-a-new-blood-test-for-the-diagnosis-of-fibrotic-nash
#20
J Boursier, R Anty, L Vonghia, V Moal, T Vanwolleghem, C M Canivet, S Michalak, S Bonnafous, P Michielsen, F Oberti, A Iannelli, L Van Gaal, S Patouraux, O Blanchet, A Verrijken, P Gual, M-C Rousselet, A Driessen, G Hunault, S Bertrais, A Tran, P Calès, S Francque
BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest...
March 25, 2018: Alimentary Pharmacology & Therapeutics
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