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Mingzuo Jiang, Nan Wu, Xi Chen, Weijie Wang, Yi Chu, Hao Liu, Wenjiao Li, Di Chen, Xiaowei Li, Bing Xu
Nonalcoholic fatty liver disease (NAFLD) and its pathologically more severe form, nonalcoholic steatohepatitis (NASH), have become prevalent worldwide and carry an increased risk of developing hepatocellular carcinoma and other metabolic diseases. Diverse animal models have been proposed to replicate particular characteristics of NAFLD and NASH and have provided significant clues to the critical molecular targets of NASH treatment. In this review, we summarize the histopathology, pathogenesis, and molecular basis of NAFLD progression and discuss the benchmark animal models of NAFLD/NASH...
March 15, 2019: Journal of International Medical Research
Bianca M Arendt, Anastasia Teterina, Paulina Pettinelli, Elena M Comelli, David W L Ma, Scott K Fung, Ian D McGilvray, Sandra E Fischer, Johane P Allard
OBJECTIVE: The aim of this study was to determine whether hepatic gene expression related to hepatocellular carcinoma (HCC) is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional study, the associations between hepatic gene expression and liver histology, insulin resistance, anthropometrics, diet, and physical activity were assessed in patients with non-alcoholic steatohepatitis (NASH; n = 19) or simple steatosis (SS; n = 20)...
December 13, 2018: Nutrition
Kazutoshi Yamada, Eishiro Mizukoshi, Takuya Seike, Rika Horii, Takeshi Terashima, Noriho Iida, Masaaki Kitahara, Hajime Sunagozaka, Kuniaki Arai, Tatsuya Yamashita, Masao Honda, Toshinari Takamura, Kenichi Harada, Shuichi Kaneko
BACKGROUND & AIMS: Accurate diagnosis of nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD) is clinically important. Therefore, there is a need for easier ways of diagnosing NASH. In this study, we investigated the serum fatty acid composition and evaluated the possibility of using the serum fatty acid composition as a diagnostic marker of NASH. METHODS: The subjects were 78 NAFLD patients (nonalcoholic fatty liver (NAFL): 30, NASH: 48) and 24 healthy individuals...
March 12, 2019: Journal of Gastroenterology and Hepatology
Patrick H Alizai, Isabella Lurje, Andreas Kroh, Sophia Schmitz, Tom Luedde, Julia Andruszkow, Ulf P Neumann, Florian Ulmer
Background: More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. Methods: In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic capacity of cytochrome P450 1A2)...
2019: Gastroenterology Research and Practice
Giuseppina Palladini, Laura G Di Pasqua, Clarissa Berardo, Veronica Siciliano, Plinio Richelmi, Stefano Perlini, Andrea Ferrigno, Mariapia Vairetti
Animal models of obstructive cholestasis and ischemia/reperfusion damage have revealed the functional heterogeneity of liver lobes. This study evaluates this heterogeneity in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rat models. Twelve-week-old Obese and Lean male Zucker rats were used for NAFLD. Eight-week-old male Wistar rats fed with 8-week methionine-choline-deficient (MCD) diet and relative control diet were used for NASH. Gelatinase (MMP-2; MMP-9) activity and protein levels, tissue inhibitors of metalloproteinase (TIMPs), reactive oxygen species (ROS), and thiobarbituric acid-reactive substances (TBARS) were evaluated in the left (LL), median (ML), and right liver (RL) lobes...
2019: Canadian Journal of Gastroenterology & Hepatology
Elena Buzzetti, Salvatore Petta, Roberta Manuguerra, Tu Vinh Luong, Daniela Cabibi, Elena Corradini, Antonio Craxì, Massimo Pinzani, Emmanuel Tsochatzis, Antonello Pietrangelo
BACKGROUND AND AIMS: Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron-overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD. METHODS: We selected 468 patients with biopsy-proven NAFLD from two European centres...
March 9, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Jung Gyu Park, Jong Soo Mok, Young In Han, Tae Sub Park, Keon Wook Kang, Cheol Soo Choi, Hee Dong Park, Joonghoon Park
Nonalcoholic fatty liver disease (NAFLD) is a global health problem that is associated with various metabolic disorders. Telmisartan is a potential treatment for NAFLD due to its ability to improve insulin sensitivity and decrease hepatic fat accumulation via modulation of PPARγ, and to suppress hepatic fibrosis by blocking angiotensin II receptors. However, the underlying mechanisms of action of telmisartan have yet to be fully elucidated. In the present study, diabetic nonalcoholic steatohepatitis (NASH) mice (STAM mice) received daily administrations of telmisartan for 6 weeks to assess the improvements in NASH...
March 8, 2019: Scientific Reports
Diana Barb, Fernando Bril, Srilaxmi Kalavalapalli, Kenneth Cusi
CONTEXT: The relationship between plasma FGF21, insulin resistance and steatohepatitis has not been systematically assessed. OBJECTIVE: To determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with NAFLD. DESIGN AND SETTING: Cross-sectional study in a University Hospital.Patients Interventions and Main Outcome MeasuresPatients with BMI>25 (n=187) underwent: (a) euglycemic hyperinsulinemic clamp to assess tissue specific insulin resistance; (b) liver magnetic resonance spectroscopy (1H-MRS) for intrahepatic triglyceride (IHTG) quantification, (c) liver biopsy (if NAFLD present; n=146); and (d) fasting plasma FGF21 levels...
March 8, 2019: Journal of Clinical Endocrinology and Metabolism
Yimin Yin, Huanhuan Liu, Zicong Zheng, Rongrong Lu, Zhuoqin Jiang
Genistein plays an active role in improving nonalcoholic fatty liver disease (NAFLD). This study is designed to investigate the effect of genistein on liver inflammation in rats with nonalcoholic steatohepatitis (NASH). Forty SPF male SD rats were randomly divided into normal group, model group, genistein low-dose group (0.1% wt/wt) and high-dose group (0.2% wt/wt) with 10 rats in each group. After 12 weeks' feeding, liver tissues and serum samples of rats were taken, and HE staining was used to perform pathological examination of liver tissues, then the degree of inflammatory infiltration was observed and NAFLD activity score(NAS) was calculated...
March 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Priya Handa, Sunil Thomas, Vicki Morgan-Stevenson, Bryan D Maliken, Eric Gochanour, Sarag Boukhar, Matthew M Yeh, Kris V Kowdley
We have previously demonstrated that iron overload in hepatic reticuloendothelial system cells (RES) is associated with severe nonalcoholic steatohepatitis (NASH) and advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Recruited myeloid-derived macrophages have gained a pivotal position as drivers of NASH progression and fibrosis. In this study, we used bone marrow-derived macrophages (BMDM) from C57Bl6 mice as surrogates for recruited macrophages and examined the effect of iron on macrophage polarization...
March 5, 2019: Journal of Leukocyte Biology
Kee-Huat Chuah, Wan Nur Illyana Wan Yusoff, Pavai Sthaneshwar, Nik Raihan Nik Mustapha, Sanjiv Mahadeva, Wah-Kheong Chan
INTRODUCTION: MACK-3 (combination of hoMa, Ast and CK18) was reported to be a good biomarker for the diagnosis of fibrotic non-alcoholic steatohepatitis (NASH). However, there is no external validation to date. AIM: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH. METHODOLOGY: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18)...
March 1, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Stefania Lama, Daniela Vanacore, Nadia Diano, Carla Nicolucci, Sonia Errico, Marcello Dallio, Alessandro Federico, Carmelina Loguercio, Paola Stiuso
Bisphenol A (BPA) and silybin are considered xenoestrogens and could interfere with the action of endogenous hormones. It was demonstrated a higher level of BPA in plasma of nonalcoholic steatohepatitis (NASH) patients, compared to those with steatosis (NAFL). We investigated the effect of BPA and silybin, alone or in combination, on proliferation, oxidative stress and steroid metabolism in HepG2 grown in high glucose concentration medium (H-HepG2). Cell viability was assessed by adding 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)...
March 1, 2019: Scientific Reports
Joe L Rowles, Aiguo Han, Rita J Miller, Jamie R Kelly, Catherine C Applegate, Matthew A Wallig, William D O'Brien, John W Erdman
Untreated nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) lead to irreversible liver damage. We hypothesized that a low-fat diet (LFD) or a high-fat diet (HFD) with soy protein isolate (SPI) would be an effective intervention to halt or reverse NAFLD progression. To test these hypotheses, we conducted 2 studies. In the first study, we fed an HFD to 7-week-old C57BL/6J mice to induce NAFLD compared to an LFD (control). Hepatic steatosis was monitored by quantitative ultrasound (QUS) scans (in vivo and ex vivo)...
December 14, 2018: Nutrition Research
Brandon J Perumpail, Andrew A Li, Nimy John, Sandy Sallam, Neha D Shah, Waiyee Kwong, George Cholankeril, Donghee Kim, Aijaz Ahmed
Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method for NAFLD due to its ability to retard and/or reverse dysbiosis and restore normal gut flora. A thorough review of medical literature was completed from inception through July 10, 2018 on the PubMed database by searching for key terms such as NAFLD, probiotics, dysbiosis, synbiotics, and nonalcoholic steatohepatitis (NASH)...
February 25, 2019: Diseases (Basel)
Nathan Kuk, Alexander Hodge, Ying Sun, Jeanne Correia, Majid Alhomrani, Chrishan Samuel, Gregory Moore, Rebecca Lim, William Sievert
BACKGROUND: Non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. Currently lifestyle modification is the only effective treatment. We have shown that human amnion epithelial cells (hAECs) reduce inflammation and fibrosis in toxin-induced liver injury models. We examined the effect of these cells and the soluble factors released by the cells into culture medium (hAEC conditioned medium, hAEC-CM) in a diet-induced murine NASH model. METHODS: C57BL/6J male mice received a Western 'fast food diet' (FFD) for 42 weeks...
March 1, 2019: Journal of Gastroenterology and Hepatology
Jingxin Zhou, Jun Liu, Huiping Sheng, Ningning You, Jin Chen, Xiaoxiao Mi, Wenjun Yang, Shufei Zang, Junping Shi
INTRODUCTION: Haptoglobin (Hp) genotypes were reported as an independent risk factor for metabolic diseases. This study aimed to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 441 subjects (NAFLD group, n = 272; healthy control, n = 169) were recruited, and their clinical biochemical parameters were measured in all subjects. Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes...
February 28, 2019: Advances in Therapy
Tea L Laursen, Christoffer A Hagemann, Chunshan Wei, Konstantin Kazankov, Karen L Thomsen, Filip K Knop, Henning Grønbæk
Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), is important in NAFLD...
February 27, 2019: World Journal of Hepatology
Grietje H Prins, Theerut Luangmonkong, Dorenda Oosterhuis, Henricus A M Mutsaers, Frank J Dekker, Peter Olinga
Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder closely related to metabolic syndrome. NAFLD can progress to an inflammatory state called non-alcoholic steatohepatitis (NASH), which may result in the development of fibrosis and hepatocellular carcinoma. To develop therapeutic strategies against NAFLD, a better understanding of the molecular mechanism is needed. Current in vitro NAFLD models fail to capture the essential interactions between liver cell types and often do not reflect the pathophysiological status of patients...
February 27, 2019: Nutrients
Akiko Sakasai-Sakai, Takanobu Takata, Jun-Ichi Takino, Masayoshi Takeuchi
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins...
February 22, 2019: Nutrients
Conrado M Fernández Rodríguez, Rocío Aller, María Luisa Gutiérrez García, Javier Ampuero, Judith Gómez-Camarero, Rosa M ª Martín-Mateos, Diego Burgos-Santamaría, José Miguel Rosales, Patricia Aspichueta, Xabier Buque, Mercedes Latorre, Raúl J Andrade, Manuel Hernández-Guerra, Manuel Romero-Gómez
BACKGROUND: recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, and renal and cardiac disease. Uric acid is an endogenous danger signal and activator of the inflammasome, and has been independently associated with an increased risk of cirrhosis. AIM AND METHODS: six hundred and thirty-four patients from the nation-wide HEPAMET registry with biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia is related with advanced liver damage in patients with non-alcoholic fatty liver disease (NAFLD)...
February 27, 2019: Revista Española de Enfermedades Digestivas
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