title: From NAFLD to NASH to cirrhosis-new insights into disease mechanisms.
abstract: NAFLD has evolved as a serious public health problem in the USA and around the world. In fact, NASH-the most serious form of NAFLD-is predicted to become the leading cause of liver transplantation in the USA by the year 2020. The pathogenesis of NAFLD and NASH, in particular the mechanisms responsible for liver injury and fibrosis, is the result of a complex interplay between host and environmental factors, and is at the centre of intense investigation. In this Review, we focus on recently uncovered aspects of the genetic, biochemical, immunological and molecular events that are responsible for the development and progression of this highly prevalent and potentially serious disease. These studies bring new insight into this complex disorder and have led to the development of novel therapeutic and diagnostic strategies that might enable a personalized approach in the management of this disease.
authors: Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0715, USA.
authors: Alexander
authors: A
authors: Wree
authors: Lori
authors: L
authors: Broderick
authors: Ali
authors: A
authors: Canbay
authors: Hal M
authors: HM
authors: Hoffman
authors: Ariel E
authors: AE
authors: Feldstein
mesh_terms: D004032:Diet; D018450:Disease Progression; D004777:Environment; D005234:Fatty Liver / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D005823:Genetics; D014943:Global Health; D006801:Humans; D007107:Immune System; D065626:Non-alcoholic Fatty Liver Disease; D057285:Precision Medicine; D015995:Prevalence
references: J Pharmacol Exp Ther. 2004 Mar;308(3):1191-6
references: 14617689
references: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12511-6
references: 16895997
references: J Clin Invest. 2005 Oct;115(10):2843-54
references: 16184193
references: Nature. 2012 Feb 01;482(7384):179-85
references: 22297845
references: Trends Microbiol. 2001 Mar;9(3):113-4
references: 11303500
references: Gastroenterology. 2010 Nov;139(5):1567-76, 1576.e1-6
references: 20708005
references: Gut. 2009 May;58(5):704-20
references: 19359436
references: J Hepatol. 2012 Apr;56(4):952-64
references: 22173168
references: Clin Liver Dis. 2012 Aug;16(3):631-45
references: 22824485
references: Front Physiol. 2012 May 22;3:138
references: 22661952
references: Hepatology. 2014 Mar;59(3):898-910
references: 23813842
references: Nature. 2010 Oct 14;467(7317):863-7
references: 20944749
references: Nutrition. 2007 Jan;23(1):46-52
references: 17140767
references: Gastroenterology. 2008 May;134(6):1655-69
references: 18471545
references: J Biol Chem. 2007 Sep 14;282(37):27141-27154
references: 17626006
references: Infect Immun. 2002 Jul;70(7):3433-42
references: 12065483
references: Hepatology. 2007 Nov;46(5):1509-18
references: 17705260
references: Semin Liver Dis. 2008 Nov;28(4):339-50
references: 18956290
references: J Biol Chem. 2009 Feb 27;284(9):5637-44
references: 19119140
references: Hepatology. 2003 Dec;38(6):1529-39
references: 14647064
references: Hepatology. 2013 May;57(5):1773-83
references: 23319235
references: Hepatology. 2007 Oct;46(4):1081-90
references: 17654743
references: Diabetes Metab. 2010 Jun;36(3):244-6
references: 20483648
references: Hepatology. 2008 Jul;48(1):322-35
references: 18506843
references: Clin Nutr. 2006 Oct;25(5):816-23
references: 16677739
references: Cell. 2010 Mar 19;140(6):805-20
references: 20303872
references: Hepatology. 2008 May;47(5):1495-503
references: 18220271
references: Int J Cancer. 2011 May 15;128(10):2436-43
references: 21128245
references: Am J Clin Nutr. 2009 Jun;89(6):1760-5
references: 19403641
references: J Hepatol. 2011 Nov;55(5):1086-94
references: 21354232
references: Hepatology. 2013 Jun;57(6):2525-31
references: 23390127
references: Gut. 2012 Sep;61(9):1323-9
references: 22427237
references: J Hepatol. 2013 Sep;59(3):563-70
references: 23665282
references: Nat Rev Gastroenterol Hepatol. 2012 Feb 21;9(3):123
references: 22349167
references: Hepatology. 2010 Nov;52(5):1836-46
references: 21038418
references: Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):554-60
references: 22795319
references: Proteomics. 2009 Jun;9(12):3244-56
references: 19562798
references: Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):446-52
references: 23657151
references: J Lipid Res. 2010 Oct;51(10):3046-54
references: 20631297
references: Hepatology. 2008 Feb;47(2):729-36
references: 18167066
references: Nat Immunol. 2011 May;12(5):408-15
references: 21478880
references: J Leukoc Biol. 2009 Sep;86(3):513-28
references: 19542050
references: Hepatology. 2008 Oct;48(4):1224-31
references: 18792393
references: Hepatology. 2013 Feb;57(2):577-89
references: 22987396
references: J Hepatol. 2009 Nov;51(5):918-24
references: 19765850
references: Prostaglandins Other Lipid Mediat. 2009 Sep;89(3-4):126-30
references: 19737659
references: Gastroenterology. 2002 Oct;123(4):1323-30
references: 12360492
references: J Clin Invest. 2009 Nov;119(11):3329-39
references: 19855132
references: Hepatology. 2004 Jul;40(1):185-94
references: 15239102
references: Nature. 2009 Apr 30;458(7242):1131-5
references: 19339967
references: J Biol Chem. 2009 Oct 30;284(44):30039-48
references: 19734538
references: Gastroenterology. 2011 Feb;140(2):697-708.e4
references: 20727895
references: Hepatology. 2011 Jul;54(1):133-44
references: 21488066
references: N Engl J Med. 2011 Jan 6;364(1):60-70
references: 21208109
references: Physiol Rev. 2010 Jan;90(1):23-46
references: 20086073
references: J Lipid Res. 2010 Jul;51(7):1696-703
references: 20185414
references: Histopathology. 2012 Aug;61(2):141-52
references: 22372457
references: Hepatology. 2007 Jun;45(6):1366-74
references: 17476695
references: FASEB J. 2010 Mar;24(3):731-9
references: 19841034
references: Digestion. 2011;83(1-2):124-33
references: 21042023
references: Physiol Rev. 2010 Jul;90(3):1165-94
references: 20664081
references: Cell Death Differ. 2012 Dec;19(12):2003-14
references: 22814620
references: Nat Med. 2011 Feb;17(2):179-88
references: 21217695
references: Gastroenterology. 1999 Jun;116(6):1413-9
references: 10348825
references: Gastroenterology. 2011 Dec;141(6):2176-87
references: 21878202
references: Hepatology. 2001 Dec;34(6):1158-63
references: 11732005
references: Clin Sci (Lond). 2004 Jun;106(6):635-43
references: 14720121
references: J Gastroenterol Hepatol. 2009 May;24(5):703-6
references: 19646010
references: Hepatology. 2010 Jan;51(1):130-41
references: 20034047
references: Obes Facts. 2013;6(1):48-56
references: 23429241
references: Br J Nutr. 2011 Jul;106(1):79-86
references: 21396140
references: Pathol Oncol Res. 2011 Dec;17(4):791-800
references: 21773880
references: Eur J Gastroenterol Hepatol. 2009 Jun;21(6):673-80
references: 19318971
references: Hepatology. 2010 Jun;51(6):1961-71
references: 20301112
references: Hum Pathol. 2004 Sep;35(9):1070-82
references: 15343508
references: Arch Biochem Biophys. 2007 Jun 15;462(2):245-53
references: 17475204
references: Hepatology. 2004 Feb;39(2):273-8
references: 14767974
references: Gastroenterology. 2004 Oct;127(4):1189-97
references: 15480996
references: Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):135-41
references: 22959954
references: J Immunol. 2002 Jan 15;168(2):554-61
references: 11777946
references: Diabetes. 2007 Jul;56(7):1761-72
references: 17456850
references: Gastroenterology. 2005 Jul;129(1):113-21
references: 16012941
references: J Hepatol. 2003 Dec;39(6):978-83
references: 14642615
references: PLoS One. 2013;8(2):e56100
references: 23409132
references: J Hepatol. 2007 Oct;47(4):571-9
references: 17644211
references: Lab Invest. 2012 May;92(5):713-23
references: 22411067
references: J Hepatol. 2012 Sep;57(3):642-54
references: 22634126
references: J Clin Immunol. 1999 Jan;19(1):1-11
references: 10080100
references: Curr Top Dev Biol. 2007;78:217-45
references: 17338918
references: J Hepatol. 2012 Mar;56(3):663-70
references: 22027586
references: Am J Clin Nutr. 2006 Jun;83(6 Suppl):1483S-1493S
references: 16841858
references: Hepatology. 2007 Jun;45(6):1343-6
references: 17538963
references: J Clin Invest. 2012 Oct;122(10):3476-89
references: 22945633
references: Gut. 2012 Jul;61(7):1058-67
references: 22253482
references: Cell Metab. 2013 Jan 8;17(1):141-52
references: 23312289
references: Am J Clin Nutr. 2012 Feb;95(2):283-9
references: 22205311
references: Am J Clin Nutr. 2007 Jun;85(6):1511-20
references: 17556686
references: Lab Invest. 2003 May;83(5):655-63
references: 12746475
references: Aliment Pharmacol Ther. 2011 Aug;34(3):274-85
references: 21623852
references: J Clin Invest. 2003 Jul;112(2):152-9
references: 12865404
references: BMC Gastroenterol. 2010 May 28;10:52
references: 20509914
references: World J Gastroenterol. 2011 Apr 7;17(13):1725-31
references: 21483633
references: Am J Clin Nutr. 2006 Jun;83(6 Suppl):1505S-1519S
references: 16841861
references: Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1248-57
references: 19359429
references: J Hepatol. 1999 Sep;31(3):430-4
references: 10488700
references: J Gastroenterol. 2010 Dec;45(12):1247-54
references: 20596733
references: Clin Sci (Lond). 2013 Feb;124(4):279-87
references: 22970906
references: Hepatology. 2012 Oct;56(4):1291-9
references: 22505276
references: Gastroenterology. 2003 Aug;125(2):437-43
references: 12891546
references: Hepatology. 2010 Jun;51(6):1998-2007
references: 20512988
references: PLoS One. 2012;7(4):e35979
references: 22558291
references: J Assoc Physicians India. 2006 Apr;54:309-19
references: 16944615
references: J Hepatol. 2012 Apr;56(4):944-51
references: 22023985
references: Biochem Biophys Res Commun. 2008 Nov 14;376(2):271-6
references: 18760996
references: Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1339-46
references: 16484678
references: Hepatology. 2010 Oct;52(4):1281-90
references: 20803499