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Fatty liver disease treatment

Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Narges Amel Zabihi, Matteo Pirro, Thomas P Johnston, Amirhossein Sahebkar
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulin-sensitizing, anti-steatotic, and anti-fibrotic properties...
October 10, 2016: Current Pharmaceutical Design
Yun-Ho Hwang, Kyung-Yun Kang, Jong-Jin Kim, Sung-Ju Lee, Young-Jin Son, Soo-Heui Paik, Sung-Tae Yee
Polygonum multiflorum (PM), a traditional Chinese medicine, is used to treat various diseases including nonalcoholic fatty liver disease and hyperlipidemia. However, the influence of PM on osteoporosis in animals is unclear. The present study investigated the antiosteoporotic effect of PM on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. Twenty-five female C3H/HeN mice were divided into five groups of five mice as follows. Sham-operated control mice received daily oral gavage of an equal volume of water, and OVX mice received daily oral gavage of water or an injection of β-estradiol or PM for 6 weeks...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Carolina Frade Magalhaes Girardin Pimentel, Michelle Lai
The progressively increasing rates of obesity have led to a worldwide epidemic of nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. It is currently the most common cause of liver disease worldwide and projected to be the leading indication for liver transplantation in the United States by 2020. NAFLD is associated with both liver-related and overall mortality. Undoubtedly, nutrition interventions are key in the treatment of NAFLD, to reverse the disease, and prevent disease progression, complications, and associated comorbidities, including cardiovascular disease and diabetes...
November 2016: Medical Clinics of North America
Peizhu Tan, Huan Liang, Junhui Nie, Yan Diao, Qi He, Baoyu Hou, Tingting Zhao, Hui Huang, Yanze Li, Xu Gao, Lingyun Zhou, Ying Liu
BACKGROUND: Alcoholic fatty liver disease (AFLD) defines an important stage in the progression of alcoholic liver disease (ALD), which is a major cause of morbidity and mortality worldwide. OBJECTIVE: To establish a mouse model of AFLD. METHODS: Male C57BL/6 mice were divided into the following two groups: (i) a control group, which was allowed free access to food and water and (ii) an alcohol-treated group, which was administered a 15% (v/v) alcohol solution instead of water...
October 14, 2016: American Journal of Drug and Alcohol Abuse
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Faisal Inayat, Zia Ur Rahman, Abu Hurairah
Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months...
August 29, 2016: Curēus
Jean-Michel Petit, Jean-Pierre Cercueil, Romaric Loffroy, Damien Denimal, Benjamin Bouillet, Coralie Fourmont, Olivier Chevallier, Laurence Duvillard, Bruno Vergès
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is very frequent in type 2 diabetes with increased risk of further development of liver fibrosis. Animal studies have shown that GLP-1 receptor agonists may reduce liver lipogenesis. However, data in humans are scarce. OBJECTIVE: To study the effect of liraglutide 1.2 mg/d on liver fat content (LFC) in patients with uncontrolled type 2 diabetes and to evaluate the factors potentially associated with liraglutide-induced modification of LFC...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
Carrie R Wong, Mindie H Nguyen, Joseph K Lim
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma (HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3...
October 7, 2016: World Journal of Gastroenterology: WJG
Hyunwoo Oh, Dae Won Jun, Waqar K Saeed, Mindie H Nguyen
The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed...
September 2016: Clinical and Molecular Hepatology
Hugo Perazzo, Jean-François Dufour
Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and hepatocellular ballooning, and may be associated with liver fibrosis leading to cirrhosis and its complications. A pharmacological approach is necessary to treat NASH because of failure to change dietary habits and lifestyle in most patients. Insulin resistance with an increased release of free fatty acids, oxidative stress and activation of inflammatory cytokines seem to be key features for disease progression. Thiazolidinediones, such as pioglitazone and antioxidant agents, such as vitamin E, were the first pharmacological options to be evaluated for NASH...
October 11, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Kerstin Schütte, Fathi Balbisi, Peter Malfertheiner
The epidemiology of hepatocellular carcinoma (HCC) has significantly changed throughout the past decade and will continue to do so in the future as a consequence of effective primary prevention and treatment of virus-related liver diseases. However, other risk factors for HCC are constantly on the rise, including alcoholic liver disease and nonalcoholic fatty liver disease. The knowledge on these and further risk factors associated with an increased risk of HCC provide the opportunity and chance for the development and implementation of successful preventive strategies to decrease the worldwide burden of HCC...
September 2016: Gastrointestinal Tumors
Kyoung Ah Kwon, Peter Chun, Jae Hong Park
PURPOSE: This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. METHODS: The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention...
September 2016: Korean Journal of Pediatrics
Stefan Z Lutz, Andreas Peter, Fausto Machicao, Apostolia Lamprinou, Jürgen Machann, Fritz Schick, Ingmar Königsrainer, Alfred Königsrainer, Andreas Fritsche, Harald Staiger, Hans-Ulrich Häring, Norbert Stefan, Konstantinos Kantartzis
CONTEXT/OBJECTIVE: Acute pharmacological inhibition of 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1), which converts cortisone into the much more potent cortisol in peripheral tissues, results in reduction of total-, visceral- and liver fat, but not of insulin resistance. We now investigated whether lifelong alterations of 11β-HSD1 activity similarly affect these cardiometabolic risk parameters, by studying single nucleotide polymorphisms (SNPs) in the 11β-HSD1-coding gene (HSD11B1)...
October 7, 2016: Journal of Clinical Endocrinology and Metabolism
Sophie Restellini, Olivier Chazouillères, Jean-Louis Frossard
Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders, reported both in Crohn's disease (CD) and ulcerative colitis (UC). They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions. Fatty liver is considered as the most common hepatobiliary complication in IBD whilst primary sclerosing cholangitis (PSC) the most specific one. Less frequently, IBD-associated hepatobiliary disorders include: autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis (PBC), hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, and liver abscess...
October 6, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Xi-Xi He, Xiao-Li Wu, Ren-Pin Chen, Chao Chen, Xiao-Gang Liu, Bin-Jiao Wu, Zhi-Ming Huang
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome with the main characteristic of diffuse liver cells with fatty changes. The clinical evolution of NAFLD includes simple non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), liver fibrosis and cirrhosis, and even hepatocellular carcinoma. METHODS AND FINDINGS: We conducted this review to identify the effectiveness of omega-3 polyunsaturated fatty acids (ω-3 PUFA) in NAFLD. We searched PubMed, Cochrane Library and Embase...
2016: PloS One
Stergios A Polyzos, Jannis Kountouras, Christos S Mantzoros
The association of obesity with nonalcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. Form an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC)...
October 6, 2016: Minerva Endocrinologica
Nirvair S Kelley
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes, cardiovascular disease, and liver failure. Treatment with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) produced variable success in improving NAFLD. The purpose of this review is to determine if n-3 LCPUFA will decrease markers of NAFLD, compare the efficacies of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and identify factors that contribute to discrepancies in results...
October 6, 2016: Metabolic Syndrome and related Disorders
Yan Zhu, Hongxia Liu, Min Zhang, Grace L Guo
The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC). A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved...
September 2016: Acta Pharmaceutica Sinica. B
Ewa Harasim-Symbor, Karolina Konstantynowicz-Nowicka, Adrian Chabowski
Synthetic and natural glucocorticoids are able to highly modify liver lipid metabolism, which is possibly associated with Nonalcoholic Fatty Liver Disease development. We have assessed changes in lipid and sphingolipid contents in hepatocytes, lipid composition and saturation status as well as the expression of proteins involved in fatty acid transport after both dexamethasone and palmitate treatments. The experiments were conducted on primary rat hepatocytes, incubated with either dexamethasone and/or palmitic acid during short (16h) and prolonged (40h) exposure...
October 5, 2016: Journal of Molecular Endocrinology
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