Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) is used to treat a variety of chronic inflammatory and neoplastic diseases. However, it can induce hepatotoxicity such as microvesicular steatosis and necrosis. To explore the mechanisms of MTX-induced hepatic steatosis, we used microarray analysis to profile the gene expression patterns of mouse liver after MTX treatment. MTX was administered orally as a single dose of 10mg/kg (low dose) or 100 mg/kg (high dose) to ICR mice, and the livers were obtained 6 h, 24 h, and 72 h after treatment. Serum alanine aminotransferase, aspartate aminotransferase and triacylglycerol levels were not significantly altered in the experimental animals. Signs of steatosis were observed at 24 h after administration of high dose of MTX. From microarray data analysis, 908 genes were selected as MTX-responsive genes (P<0.05, two-way ANOVA; cutoff > or =1.5-fold). Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis revealed that the predominant biological processes associated with these genes are response to unfolded proteins, phosphate metabolism, and cellular lipid metabolism. Functional categorization of these genes identified 28 genes involved in lipid metabolism that was interconnected with the biological pathways of biosynthesis, catabolism, and transport of lipids and fatty acids. Taken together, these data provide a better understanding of the molecular mechanisms of MTX-induced steatogenic hepatotoxicity, and useful information for predicting hepatotoxicity through pattern recognition.
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PMID:Gene expression profiles of murine fatty liver induced by the administration of methotrexate. 1850 57

Methotrexate (MTX) is commonly used to treat individuals with rheumatological and dermatologic disorders. Current American College of Rheumatology (ACR) and American Association of Dermatology (AAD) guidelines identify diabetes and obesity as risk factors for MTX-induced liver injury. Both diabetes and obesity are components of the metabolic syndrome, and are also risk factors for nonalcoholic fatty liver disease (NAFLD). NAFLD affects approximately 40% of the U.S. population, and those with more advanced NAFLD (i.e., nonalcoholic steatohepatitis with or without fibrosis) are likely to develop progressive liver disease. As such, individuals who are treated with MTX may need to be screened for advanced NAFLD, as this may put them at an increased risk of MTX-induced liver injury. In this mini-review, we review the current ACR and AAD guidelines on MTX hepatotoxicity, discuss the evidence (or lack thereof) of the impact of metabolic risk factors on MTX-induced liver injury and highlight the areas that need further research.
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PMID:Methotrexate Hepatotoxicity and the Impact of Nonalcoholic Fatty Liver Disease. 2886 76

Liver and biliary track diseases are common extraintestinal manifestations of inflammatory bowel disease (IBD), reported both in Crohn's disease and ulcerative colitis, and may occur at any time during the natural course of the disease. Their etiology is mainly related to pathophysiological changes induced by IBD, and secondary, due to drugs used in IBD. Fatty liver is considered as the most frequent hepatobiliary manifestation in IBD, while primary sclerosing cholangitis (PSC) is the most correlated hepatobiliary disorder and is more prevalent in patients with ulcerative colitis. PSC can cause serious complications from the liver, biliary tree, and gallbladder and can lead to liver failure. Less frequently, IBD-associated hepatobiliary manifestations include cholelithiasis, granulomatous hepatitis, portal vein thrombosis, IgG4-related cholangiopathy, pyogenic liver abscess, hepatic amyloidosis and primary biliary cirrhosis. Most of the drugs used for IBD treatment may cause liver toxicity. Methotrexate and thiopurines carry the higher risk for hepatotoxicity, and in many cases, dose adjustment may normalize the liver biochemical tests. Reactivation of hepatitis B and C virus during immunosuppressive use, especially during use of biological agents, is a major concern, and adequate screening, vaccination and prophylactic treatment is warranted.
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PMID:Hepatobiliary Manifestations and Complications in Inflammatory Bowel Disease: A Review. 2970 74