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Review

Drug-induced steatohepatitis

, , &
Pages 193-204 | Received 03 Jul 2016, Accepted 05 Oct 2016, Published online: 27 Oct 2016

References

  • Farrell GC. Drugs and steatohepatitis. Semin Liver Dis. 2002;22:185–194.
  • Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–285.
  • Grieco A, Forgione A, Miele L, et al. Fatty liver and drugs. Eur Rev Med Pharmacol Sci. 2005;9:261–263.
  • Rabinowich L, Shibolet O. Drug induced steatohepatitis: an uncommon culprit of a common disease. Biomed Res Int. 2015;2015:168905.
  • Patel V, Sanyal AJ, Sterling R. Clinical presentation and patient evaluation in nonalcoholic fatty liver disease. Clin Liver Dis. 2016;20:277–292.
  • Begriche K, Massart J, Robin MA, et al. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol. 2011;54:773–794.
  • Schumacher JD, Guo GL. Mechanistic review of drug-induced steatohepatitis. Toxicol Appl Pharmacol. 2015;289:40–47.
  • Fong Y, Bentrem DJ. CASH (chemotherapy-associated steatohepatitis) costs. Ann Surg. 2006;243:8–9.
  • Wahlang B, Beier JI, Clair HB, et al. Toxicant-associated steatohepatitis. Toxicol Pathol. 2013;41:343–360.
  • Jaeschke H, Gores GJ, Cederbaum AI, et al. Mechanisms of hepatotoxicity. Toxicol Sci. 2002;65:166–176.
  • Kazmi F, Hensley T, Pope C, et al. Lysosomal sequestration (trapping) of lipophilic amine (cationic amphiphilic) drugs in immortalized human hepatocytes (Fa2N-4 cells). Drug Metab Dispos. 2013;41:897–905.
  • Lowe R, Mussa HY, Nigsch F, et al. Predicting the mechanism of phospholipidosis. J Cheminform. 2012;4:2.
  • Shayman JA, Abe A. Drug induced phospholipidosis: an acquired lysosomal storage disorder. Biochim Biophys Acta. 2013;1831:602–611.
  • Amacher DE. The mechanistic basis for the induction of hepatic steatosis by xenobiotics. Expert Opin Drug Metab Toxicol. 2011;7:949–965.
  • Cole LK, Jacobs RL, Vance DE. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology. 2010;52:1258–1265.
  • Zhao F, Xie P, Jiang J, et al. The effect and mechanism of tamoxifen-induced hepatocyte steatosis in vitro. Int J Mol Sci. 2014;15:4019–4030.
  • Moya M, Gomez-Lechon MJ, Castell JV, et al. Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile. Chem Biol Interact. 2010;184:376–387.
  • Amacher DE. Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies. Toxicology. 2011;279:10–18.
  • Labbe G, Pessayre D, Fromenty B. Drug-induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundam Clin Pharmacol. 2008;22:335–353.
  • Kawano Y, Cohen DE. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. J Gastroenterol. 2013;48:434–441.
  • Goldberg IJ, Eckel RH, Abumrad NA. Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways. J Lipid Res. 2009;50(Suppl):S86–90.
  • Thomson DM, Winder WW. AMP-activated protein kinase control of fat metabolism in skeletal muscle. Acta Physiol (Oxf). 2009;196:147–154.
  • Blas-Garcia A, Apostolova N, Ballesteros D, et al. Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells. Hepatology. 2010;52:115–125.
  • Zhou J, Febbraio M, Wada T, et al. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology. 2008;134:556–567.
  • Sahini N, Selvaraj S, Borlak J. Whole genome transcript profiling of drug induced steatosis in rats reveals a gene signature predictive of outcome. PLoS One. 2014;9:e114085.
  • Benet M, Moya M, Donato MT, et al. A simple transcriptomic signature able to predict drug-induced hepatic steatosis. Arch Toxicol. 2014;88:967–982.
  • Liu Z, Wang Y, Borlak J, et al. Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades. Sci Rep. 2016;6:23709.
  • Diehl AM. Lessons from animal models of NASH. Hepatol Res. 2005;33:138–144.
  • Kohli R, Feldstein AE. NASH animal models: are we there yet? J Hepatol. 2011;55:941–943.
  • Larter CZ, Yeh MM. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol. 2008;23:1635–1648.
  • London RM, George J. Pathogenesis of NASH: animal models. Clin Liver Dis. 2007;11:55–74, viii.
  • Choi YJ, Lee CH, Lee KY, et al. Increased hepatic fatty acid uptake and esterification contribute to tetracycline-induced steatosis in mice. Toxicol Sci. 2015;145:273–282.
  • Larosche I, Letteron P, Fromenty B, et al. Tamoxifen inhibits topoisomerases, depletes mitochondrial DNA, and triggers steatosis in mouse liver. J Pharmacol Exp Ther. 2007;321:526–535.
  • Lelliott CJ, Lopez M, Curtis RK, et al. Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis. Faseb J. 2005;19:1108–1119.
  • Gudbrandsen OA, Rost TH, Berge RK. Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver. J Lipid Res. 2006;47:2223–2232.
  • Van Summeren A, Renes J, Lizarraga D, et al. Screening for drug-induced hepatotoxicity in primary mouse hepatocytes using acetaminophen, amiodarone, and cyclosporin a as model compounds: an omics-guided approach. Omics. 2013;17:71–83.
  • Le TT, Urasaki Y, Pizzorno G. Uridine prevents tamoxifen-induced liver lipid droplet accumulation. BMC Pharmacol Toxicol. 2014;15:27.
  • Deschamps D, DeBeco V, Fisch C, et al. Inhibition by perhexiline of oxidative phosphorylation and the beta-oxidation of fatty acids: possible role in pseudoalcoholic liver lesions. Hepatology. 1994;19:948–961.
  • Berson A, De Beco V, Letteron P, et al. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology. 1998;114:764–774.
  • Tong V, Teng XW, Chang TK, et al. Valproic acid II: effects on oxidative stress, mitochondrial membrane potential, and cytotoxicity in glutathione-depleted rat hepatocytes. Toxicol Sci. 2005;86:436–443.
  • Amacher DE, Martin BA. Tetracycline-induced steatosis in primary canine hepatocyte cultures. Fundam Appl Toxicol. 1997;40:256–263.
  • Sassa S, Sugita O, Galbraith RA, et al. Drug metabolism by the human hepatoma cell, hep G2. Biochem Biophys Res Commun. 1987;143:52–57.
  • Choi JM, Oh SJ, Lee JY, et al. Prediction of drug-induced liver injury in hepG2 cells cultured with human liver microsomes. Chem Res Toxicol. 2015;28:872–885.
  • Cui W, Chen SL, Hu KQ. Quantification and mechanisms of oleic acid-induced steatosis in HepG2 cells. Am J Transl Res. 2010;2:95–104.
  • Donato MT, Martinez-Romero A, Jimenez N, et al. Cytometric analysis for drug-induced steatosis in HepG2 cells. Chem Biol Interact. 2009;181:417–423.
  • Kamalian L, Chadwick AE, Bayliss M, et al. The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicol In Vitro. 2015;29:732–740.
  • Gerets HH, Tilmant K, Gerin B, et al. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012;28:69–87.
  • Gripon P, Rumin S, Urban S, et al. Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A. 2002;99:15655–15660.
  • Lambert CB, Spire C, Renaud MP, et al. Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009;23:466–475.
  • Antherieu S, Chesne C, Li R, et al. Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab Dispos. 2010;38:516–525.
  • Pant A, Kocarek T. Farnesol suppresses lipid accumulation in a HepaRG-based model of hepatic steatosis (1142.8). The FASEB Journal. 2014;28:1142.1148.
  • Rogue A, Antherieu S, Vluggens A, et al. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. Toxicol Appl Pharmacol. 2014;276:73–81.
  • Hannan NR, Segeritz CP, Touboul T, et al. Production of hepatocyte-like cells from human pluripotent stem cells. Nat Protoc. 2013;8:430–437.
  • Rashid ST, Corbineau S, Hannan N, et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 2010;120:3127–3136.
  • Sirenko O, Hesley J, Rusyn I, et al. High-content assays for hepatotoxicity using induced pluripotent stem cell-derived cells. Assay Drug Dev Technol. 2014;12:43–54.
  • Berger DR, Ware BR, Davidson MD, et al. Enhancing the functional maturity of induced pluripotent stem cell-derived human hepatocytes by controlled presentation of cell-cell interactions in vitro. Hepatology. 2015;61:1370–1381.
  • Yu Y, Liu H, Ikeda Y, et al. Hepatocyte-like cells differentiated from human induced pluripotent stem cells: relevance to cellular therapies. Stem Cell Res. 2012;9:196–207.
  • Wilkening S, Stahl F, Bader A. Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos. 2003;31:1035–1042.
  • Rodriguez-Antona C, Donato MT, Boobis A, et al. Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells. Xenobiotica. 2002;32:505–520.
  • Baker TK, Carfagna MA, Gao H, et al. Temporal gene expression analysis of monolayer cultured rat hepatocytes. Chem Res Toxicol. 2001;14:1218–1231.
  • Boess F, Kamber M, Romer S, et al. Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol Sci. 2003;73:386–402.
  • Suckale J, Solimena M. Pancreas islets in metabolic signaling–focus on the beta-cell. Front Biosci. 2008;13:7156–7171.
  • Bertrand F, Philippe C, Antoine PJ, et al. Insulin activates nuclear factor kappa B in mammalian cells through a Raf-1-mediated pathway. J Biol Chem. 1995;270:24435–24441.
  • Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183–190.
  • Ke B, Zhao Z, Ye X, et al. Inactivation of NF-kappaB p65 (RelA) in liver improves insulin sensitivity and inhibits cAMP/PKA pathway. Diabetes. 2015;64:3355–3362.
  • Dash A, Inman W, Hoffmaster K, et al. Liver tissue engineering in the evaluation of drug safety. Expert Opin Drug Metab Toxicol. 2009;5:1159–1174.
  • Kane BJ, Zinner MJ, Yarmush ML, et al. Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes. Anal Chem. 2006;78:4291–4298.
  • Xia L, Ng S, Han R, et al. Laminar-flow immediate-overlay hepatocyte sandwich perfusion system for drug hepatotoxicity testing. Biomaterials. 2009;30:5927–5936.
  • Domansky K, Inman W, Serdy J, et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip. 2010;10:51–58.
  • Hastings NE, Simmers MB, McDonald OG, et al. Atherosclerosis-prone hemodynamics differentially regulates endothelial and smooth muscle cell phenotypes and promotes pro-inflammatory priming. Am J Physiol Cell Physiol. 2007;293:C1824–1833.
  • Dash A, Simmers MB, Deering TG, et al. Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro. Am J Physiol Cell Physiol. 2013;304:C1053- C1063.
  • Dash A, Deering TG, Marukian S, et al., Human primary hepatocytes under controlled hemodynamics elicit induction responses to drugs at clinical cmax concentrations, 52nd Annual Meeting of the Society of ToxicologySan Antonio, Texas., 2013, pp. 10.
  • Dash A, Deering T, Marukian S et al. Physiological Hemodynamics and Transport Restore Insulin and Glucagon Responses in a Normal Glucose Milieu in Hepatocytes in Vitro. (2013) In late breaking ADA abstracts. Diabetes Vol 62 (Suppl. 1A) pLB37
  • Deering TG, Thomas JT, Blackman BR, Wamhoff BR, Dash A. Development of an in vitro model of hepatic steatosis using rat hepatocytes under controlled hemodynamics in a diabetic milieu. (2012), In AASLD Abstracts. Hepatology, Vol 56: p868A.
  • Terelius Y, Figler RA, Marukian S, et al. Transcriptional profiling suggests that nevirapine and ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31–44.
  • Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration. J Magn Reson Imaging. 2012;36:1011–1014.
  • Sasso M, Audiere S, Kemgang A, et al. Liver steatosis assessed by Controlled Attenuation Parameter (CAP) measured with the xl probe of the fibroscan: a pilot study assessing diagnostic accuracy. Ultrasound Med Biol. 2016;42:92–103.
  • Sasso M, Miette V, Sandrin L, et al. The controlled attenuation parameter (CAP): a novel tool for the non-invasive evaluation of steatosis using Fibroscan. Clin Res Hepatol Gastroenterol. 2012;36:13–20.
  • Deffieux T, Gennisson JL, Bousquet L, et al. Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography. J Hepatol. 2015;62:317–324.
  • Eddowes P, Sasso M, Fournier C, et al. Steatosis and liver stiffness measurements using transient elastography. Hepatology. 2016;64:700-700.
  • Macaluso FS, Maida M, Camma C, et al. Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C. J Hepatol. 2014;61:523–529.
  • Ballestri S, Nascimbeni F, Romagnoli D, et al. The independent predictors of NASH and its individual histological features. Insulin resistance, serum uric acid, metabolic syndrome, ALT and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment. Hepatol Res. 2016;46:1074–1087.
  • Torres DM, Harrison SA. NAFLD: predictive value of ALT levels for NASH and advanced fibrosis. Nat Rev Gastroenterol Hepatol. 2013;10:510–511.
  • Harnois F, Msika S, Sabate JM, et al. Prevalence and predictive factors of non-alcoholic steatohepatitis (NASH) in morbidly obese patients undergoing bariatric surgery. Obes Surg. 2006;16:183–188.
  • Losekann A, Weston AC, De Mattos AA, et al. Non-Alcoholic Steatohepatitis (NASH): risk factors in morbidly obese patients. Int J Mol Sci. 2015;16:25552–25559.
  • Fisher CD, Lickteig AJ, Augustine LM, et al. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos. 2009;37:2087–2094.
  • Lake AD, Novak P, Fisher CD, et al. Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos. 2011;39:1954–1960.
  • Chtioui H, Semela D, Ledermann M, et al. Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis. Liver Int. 2007;27:764–771.
  • Schattenberg JM, Czaja MJ. Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling. Redox Biol. 2014;3:7–15.
  • Hardwick RN, Clarke JD, Lake AD, et al. Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis. Toxicol Sci. 2014;142:45–55.
  • Ijssennagger N, Janssen AW, Milona A, et al. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid. J Hepatol. 2016;64:1158–1166.
  • Ding X, Thung SN, Grewal P. Steatohepatitis secondary to long-term glucocorticoid treatment for congenital adrenal hyperplasia: a potential diagnostic pitfall. Semin Liver Dis. 2013;33:389–392.
  • He J, Li G, Chen J, et al. Prolonged exposure to low-dose microcystin induces nonalcoholic steatohepatitis in mice: a systems toxicology study. Arch Toxicol. (2016). doi:10.1007/s00204-016-1681-3

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