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Alcoholic Steatohepatitis

Leon A Adams
Non-alcoholic steatohepatitis (NASH) is an increasingly common cause of cirrhosis, hepatocellular carcinoma, and liver-related death (LRD). Consequently, there is a critical need for effective drug therapy that improves clinically relevant end-points. Hepatic steatosis assessed by magnetic resonance imaging-proton density fat fraction is increasingly used in the early phase trials examining drugs with anti-steatotic effects. However, the prognostic significance of a reduction in steatosis is unknown, and thus, phase 3 trials require a histological end-point of NASH resolution without fibrosis progression...
February 19, 2019: Hepatology International
Isabel Schulien, Birgit Hockenjos, Annette Schmitt-Graeff, Markus Große Perdekamp, Marie Follo, Robert Thimme, Peter Hasselblatt
Progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to non-alcoholic steatohepatitis (NASH) is a key step of NASH pathogenesis. The AP-1 transcription factor c-Jun is an important regulator of hepatic stress responses, but its contribution to NASH pathogenesis remains poorly defined. We therefore addressed c-Jun expression in liver biopsies of patients with steatosis and NASH. The role of c-Jun during NASH pathogenesis was analyzed mechanistically in c-Jun mutant mice fed with a methionine- and choline-deficient diet (MCDD)...
February 18, 2019: Cell Death and Differentiation
Kosha J Mehta, Sebastien Je Farnaud, Paul A Sharp
Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis...
February 7, 2019: World Journal of Gastroenterology: WJG
Antje Mohs, Nadine Kuttkat, Tobias Otto, Sameh A Youssef, Alain De Bruin, Christian Trautwein
In Western countries, a rising incidence of obesity and type 2 diabetes correlates with an increase of non-alcoholic steatohepatitis (NASH)-a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). NASH is associated with chronic liver injury, triggering hepatocyte death and enhanced translocation of intestinal bacteria, leading to persistent liver inflammation through activation of Toll-like receptors and their adapter protein myeloid differentiation factor 88 (MyD88). Therefore, we investigated the role of MyD88 during progression from NASH to HCC using a mouse model of chronic liver injury (hepatocyte-specific deletion of nuclear factor κB essential modulator, Nemo; NemoΔhepa)...
February 13, 2019: Carcinogenesis
Peter Lykke Eriksen, Michael Sørensen, Henning Grønbæk, Stephen Hamilton-Dutoit, Hendrik Vilstrup, Karen Louise Thomsen
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD. METHODS: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study...
February 12, 2019: Clinics and Research in Hepatology and Gastroenterology
Osmanuddin Ahmed, Lisa Liu, Antony Gayed, Amanjit Baadh, Mikin Patel, Jordan Tasse, Ulku Turba, Bulent Arslan
Background/objectives: The purpose of this research is to analyze the past and forecast the future prevalence of Hepatitis C Virus (HCV) and Nonalcoholic Steatohepatitis (NASH) and their respective contribution to Hepatocellular Carcinoma (HCC) incidence in the setting of novel anti-viral agents and rising obesity rates in the United States. Methods: Existing data of HCV and NASH prevalence in the United States utilizing the National Health and Nutrition Examination Survey (NHANES) and Organ Procurement and Transplantation Network (OPTN) was collected and analyzed to project future prevalence trends...
January 2019: Journal of Clinical and Experimental Hepatology
Pierangelo Torquato, Danilo Giusepponi, Anna Alisi, Roberta Galarini, Desirée Bartolini, Marta Piroddi, Laura Goracci, Alessandra Di Veroli, Gabriele Cruciani, Annalisa Crudele, Valerio Nobili, Francesco Galli
Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic acid (DHA) in combination with vitamin D (VD) or with choline (CHO) and vitamin E (VE), the DHA-VD and DHA-CHO-VE trials, respectively). In the present study we verified the nutritional compliance to these DHA-based multivitamin treatments; lipidomics biomarkers of the reported outcome on NASH indicators were also investigated...
February 14, 2019: Scientific Reports
Wen Wen, Robert F Schwabe
Nearly 25% of the world's population is suffering from non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity and type 2 diabetes. NAFLD may progress to the development of non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). With efficient medical therapies lacking, modifications of life style and diet are considered the best options for the prevention and treatment of NAFLD. For the latter, it is thought that besides reducing fat, sugar and caloric intake, increasing fiber may exert beneficial effects on NAFLD, e...
February 14, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lauren Pavlik, Arie Regev, Paul A Ardayfio, Naga P Chalasani
Drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH) are two of several types of drug-induced liver injury (DILI). They can be caused by various drugs and may present as acute, potentially lethal disorders or as chronic slowly progressive liver injury. Despite the fact that they are distinct disorders, the slow progressive forms of DIS and DISH are often confused with or misdiagnosed as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), which are much more common and, by definition, not caused by drugs...
February 14, 2019: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
David Højland Ipsen, Josephine Skat-Rørdam, Maria Malvina Tsamouri, Markus Latta, Jens Lykkesfeldt, Pernille Tveden-Nyborg
Hepatic fibrosis increases mortality in humans with non-alcoholic steatohepatitis (NASH), but it remains unclear how fibrosis stage and progression affect the pathogenic mechanisms of NASH. This study investigates the transcriptional regulation and the impact of fibrosis stage, of pathways relating to hepatic lipid and cholesterol homeostasis, inflammation and fibrosis using RT-qPCR in the guinea pig NASH model. Animals were fed a chow (4% fat), a high-fat (20% fat, 0.35% cholesterol) or high-fat/high-sucrose (20% fat, 15% sucrose, 0...
February 13, 2019: Molecular Genetics and Genomics: MGG
Maxime Nachit, Isabelle A Leclercq
Skeletal muscle is a tissue that represents 30-40% of total body mass in healthy humans and contains up to 75% of total body proteins. It is thus the largest organ in non-obese subjects. The past few years have seen increasing awareness of the prognostic value of appreciating changes in skeletal muscle compartment in various chronic diseases. Hence, a low muscle mass, a low muscle function and muscle fatty infiltration are linked with poor outcomes in many pathological conditions. In particular, an affluent body of evidence links the severity, the complications and mortality of chronic liver disease (CLD) with skeletal muscle depletion...
February 14, 2019: Clinical Science (1979-)
Maiko Suzuki, Kazuyoshi Kon, Kenichi Ikejima, Kumiko Arai, Akira Uchiyama, Tomonori Aoyama, Shunhei Yamashina, Takashi Ueno, Sumio Watanabe
BACKGROUND: Co-occurrence of metabolic syndrome and chronic alcohol consumption is increasing worldwide. The present study investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA)-which has been shown to alleviate dietary steatohepatitis caused by endoplasmic reticulum (ER) stress-on chronic-plus-binge ethanol (EtOH)-induced liver injury in a mouse model of obesity. METHODS: Male KK-Ay mice (8 weeks old) were fed a Lieber-DeCarli diet (5% EtOH) for 10 days...
February 12, 2019: Alcoholism, Clinical and Experimental Research
Ľubomár Skladaný, Svetlana Adamcová Selčanová, Martin Janičko, Zuzana Bečková, Lenka Helmová, Jana Vnenčáková
INTRODUCTION: HEV infection is perceived as the cause of acute hepatitis in endemic areas. In addition, it may also manifest as a possible trigger of AD or acute-on-chronic liver failure (ACLF). OBJECTIVES: To determine the prevalence of HEV infection as a trigger of AD/ACLF in patients admitted for decompensated ACLD (dACLD). METHODS: A retrospective study; data analysis of consecutive patients with dACLD admitted to a liver unit. Study interval: August 2016 - October 2017...
September 2018: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
Rocío Aller, Beatriz Burgueño Gomez, Rebeca Sigüenza, Conrado Fernández-Rodríguez, Natalia Fernández, Beatriz Antolín, Miguel Durà, María Pina, Sara Lorenzo, Concepción García, Daniel de Luis Román
BACKGROUND AND AIMS: non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the western world. Although NAFLD prevalence is higher in patients with a BMI > 25 kg /m2, it is unclear if there are differences between overweight and obese patients. The associated biochemical, dietary and genetic parameters were compared between overweight and obese patients with NAFLD. METHODS: patients with biopsy-proven NAFLD (n = 203) were enrolled in a cross-sectional study...
February 11, 2019: Revista Española de Enfermedades Digestivas
Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon Ali, Dinan Abdelatif, Zahra Younoszai, Maria Stepanova, Zachary D Goodman, Zobair M Younossi
BACKGROUND: Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. METHODS: SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control)...
February 11, 2019: BMC Gastroenterology
Noha F Hassan, Somaia A Nada, Azza Hassan, Mona R El-Ansary, Muhammad Y Al-Shorbagy, Rania M Abdelsalam
The most epidemic liver disorder non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with hepatocellular damage. Recently, it is predictable to be the extensive cause for liver transplantation. The absence of an approved therapeutic agent for NASH is the reason for investigating saroglitazar (SAR) which showed promising effects as a dual PPAR-α/γ agonist in recent studies on NASH. Here, we aimed to investigate the effect of SAR on NASH induced in rats by the administration of high-fat emulsion (HFE) and small doses of lipopolysaccharides (LPS) for 5 weeks...
February 9, 2019: Inflammation
Ann-Christin Otto, Hongying Gan-Schreier, Xingya Zhu, Sabine Tuma-Kellner, Simone Staffer, Alexandra Ganzha, Gerhard Liebisch, Walee Chamulitrat
A defect of hepatic remodeling of phospholipids (PL) is seen in non-alcoholic fatty liver disease and steatohepatitis (NASH) indicating pivotal role of PL metabolism in this disease. The deletion of group VIA calcium-independent phospholipase A2 (iPla2β) protects ob/ob mice from hepatic steatosis (BBAlip 1861, 2016, 440-461), however its role in high-fat diet (HFD)-induced NASH is still elusive. Here, wild-type and iPla2β-null mice were subjected to chronic feeding with HFD for 6 months. We showed that protection was observed in iPla2β-null mice with an attenuation of diet-induced body and liver-weight gains, liver enzymes, serum free fatty acids as well as hepatic TG and steatosis scores...
February 5, 2019: Biochimica et biophysica acta. Molecular and cell biology of lipids
Xingya Zhu, Hongying Gan-Schreier, Ann-Christin Otto, Yuting Cheng, Simone Staffer, Sabine Tuma-Kellner, Alexandra Ganzha, Gerhard Liebisch, Walee Chamulitrat
Group VIA calcium-independent phospholipase A2 (iPla2β) is among modifier genes of non-alcoholic fatty liver disease which leads to non-alcoholic steatohepatitis (NASH). Consistently, iPla2β deletion protects hepatic steatosis and obesity in genetic ob/ob and obese mice chronically fed with high-fat diet by replenishing the loss of hepatic phospholipids (PL). As mouse feeding with methionine- and choline-deficient (MCD) diet is a model of lean NASH, we tested whether iPla2β-null mice could still be protected since PL syntheses are disturbed...
February 5, 2019: Biochimica et biophysica acta. Molecular and cell biology of lipids
Sorim Choung, Ji Min Kim, Kyong Hye Joung, Eaum Seok Lee, Hyun Jin Kim, Bon Jeong Ku
Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease. NAFLD begins with excessive lipid accumulation in the liver and progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is closely linked to dysregulated hepatic lipid metabolism. Although recent studies have reported that epidermal growth factor receptor (EGFR) signaling regulates lipid metabolism, the roles of EGFR and EGFR inhibitors as modulators of lipid metabolism are largely unknown. Here, we investigated whether inhibiting EGFR using the EGFR tyrosine kinase inhibitor (TKI) PD153035 improves NAFLD...
2019: PloS One
Emer Fitzpatrick
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease, affecting 10% of school-aged children and 44-70% of obese children and young people (CYP) in the western world. Encompassing a spectrum from simple steatosis to steatohepatitis and progressive fibrosis, the disease is rapidly becoming the most common indication for liver transplantation. The molecular pathogenesis of NAFLD remains only partially understood. Development and progression of NAFLD is influenced by genetic and nutritional factors, insulin resistance, oxidative stress, gut microbiome, bile acid metabolism and lipid/glucose handling and is closely associated with overweight and obesity...
February 8, 2019: Proceedings of the Nutrition Society
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