title: Metabolic alterations and hepatitis C: From bench to bedside.
abstract: In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.
authors.affiliation: Ming-Ling Chang, Liver Research Center, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000821:virology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000821:virology; D050171:Dyslipidemias / Q000378:metabolism / Q000821:virology; D004734:Energy Metabolism / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism / Q000821:virology; D016679:Genome, Viral; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D024821:Metabolic Syndrome / Q000378:metabolism / Q000821:virology; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D000998:Antiviral Agents; D005947:Glucose
keywords: Cardiovascular; Core; Glucose; Hepatitis C virus; Lipid; Nonstructural protein 5 A; Transgenic mice
references.citation: Arch Med Res. 2009 May;40(4):294-8
references.pmid: 19608019
references.citation: J Viral Hepat. 2004 Sep;11(5):455-8
references.pmid: 15357652
references.citation: Gastroenterology. 2006 May;130(6):1661-9
references.pmid: 16697730
references.citation: J Hepatol. 2005 Aug;43(2):235-42
references.pmid: 15964656
references.citation: Gastroenterology. 2010 Jul;139(1):120-9.e18
references.pmid: 20399780
references.citation: Hepatology. 2002 Apr;35(4):937-46
references.pmid: 11915042
references.citation: Hepatology. 2008 Nov;48(5):1396-403
references.pmid: 18830996
references.citation: Aliment Pharmacol Ther. 2015 Jan;41(2):209-17
references.pmid: 25413020
references.citation: Am J Gastroenterol. 2008 May;103(5):1136-44
references.pmid: 18477344
references.citation: Am J Gastroenterol. 2009 Mar;104(3):598-604
references.pmid: 19262519
references.citation: J Infect Dis. 2008 Jan 15;197(2):283-91
references.pmid: 18177246
references.citation: J Gastroenterol Hepatol. 2015 Feb;30(2):329-36
references.pmid: 25091195
references.citation: J Viral Hepat. 2011 Apr;18(4):e144-52
references.pmid: 21070504
references.citation: J Virol. 2014 Mar;88(6):3246-54
references.pmid: 24390321
references.citation: J Hepatol. 2015 Apr;62(1 Suppl):S87-99
references.pmid: 25920094
references.citation: J Viral Hepat. 2012 May;19(5):346-52
references.pmid: 22497814
references.citation: World J Gastroenterol. 2010 Jul 21;16(27):3427-31
references.pmid: 20632447
references.citation: Liver Int. 2011 Jan;31(1):66-74
references.pmid: 20840397
references.citation: Gastroenterology. 2011 Feb;140(2):469-77
references.pmid: 21070775
references.citation: PLoS One. 2010;5(9). pii: e12841. doi: 10.1371/journal.pone.0012841
references.pmid: 20862263
references.citation: J Gastroenterol. 2010 May;45(5):523-36
references.pmid: 20012654
references.citation: Hepatology. 2011 Dec;54(6):1936-46
references.pmid: 21858850
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15865-70
references.pmid: 14668447
references.citation: PPAR Res. 2012;2012:605302
references.pmid: 22966221
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2561-6
references.pmid: 15699349
references.citation: Aliment Pharmacol Ther. 2006 Nov 1;24(9):1349-57
references.pmid: 17059516
references.citation: World J Gastroenterol. 2014 Mar 21;20(11):2825-38
references.pmid: 24659875
references.citation: J Virol. 2008 Aug;82(16):7964-76
references.pmid: 18524832
references.citation: Hepatology. 2007 Jul;46(1):66-73
references.pmid: 17596870
references.citation: Obesity (Silver Spring). 2013 Feb;21(2):291-6
references.pmid: 23404868
references.citation: Obesity (Silver Spring). 2012 Jul;20(7):1474-80
references.pmid: 22421894
references.citation: Gut. 2015 Mar;64(3):495-503
references.pmid: 25398770
references.citation: Digestion. 2011;83(1-2):32-40
references.pmid: 20847561
references.citation: J Hepatol. 2012 Sep;57(3):492-8
references.pmid: 22634340
references.citation: Clin Gastroenterol Hepatol. 2010 Jan;8(1):72-8
references.pmid: 19686868
references.citation: J Hepatol. 2015 Feb;62(2):278-85
references.pmid: 25220251
references.citation: Aliment Pharmacol Ther. 2009 Nov 1;30(9):947-54
references.pmid: 19604179
references.citation: Hepatology. 2010 Aug;52(2):443-53
references.pmid: 20683944
references.citation: J Virol. 2011 Nov;85(22):11646-54
references.pmid: 21917952
references.citation: J Hepatol. 2007 Jun;46(6):1126-32
references.pmid: 17335930
references.citation: Int J Hepatol. 2012;2012:264017
references.pmid: 22701799
references.citation: Hepatology. 2010 Nov;52(5):1543-52
references.pmid: 20799355
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7271-6
references.pmid: 12761383
references.citation: J Biol Chem. 2014 Jul 4;289(27):18904-13
references.pmid: 24838241
references.citation: J Biol Chem. 2004 Dec 10;279(50):52772-80
references.pmid: 15452130
references.citation: World J Hepatol. 2013 Feb 27;5(2):74-81
references.pmid: 23646232
references.citation: J Gastroenterol Hepatol. 2006 Aug;21(8):1266-8
references.pmid: 16872307
references.citation: Hepatology. 2012 Nov;56(5):1681-7
references.pmid: 22619107
references.citation: J Virol. 2008 Mar;82(5):2120-9
references.pmid: 18077707
references.citation: J Hepatol. 2014 Dec;61(6):1407-17
references.pmid: 25178562
references.citation: Liver Transpl. 2008 Sep;14(9):1287-93
references.pmid: 18756451
references.citation: Int J Obes (Lond). 2007 May;31(5):871-5
references.pmid: 17047638
references.citation: Dig Liver Dis. 2012 May;44(5):419-25
references.pmid: 22277808
references.citation: Am J Gastroenterol. 2005 Mar;100(3):711-5
references.pmid: 15743372
references.citation: Biochem J. 2004 Mar 15;378(Pt 3):919-28
references.pmid: 14670077
references.citation: J Viral Hepat. 2009 Oct;16(10):689-96
references.pmid: 19486470
references.citation: Gut. 2012 Jan;61(1):128-34
references.pmid: 21873466
references.citation: Clin Gastroenterol Hepatol. 2008 May;6(5):584-9
references.pmid: 18455698
references.citation: Arch Virol. 2010 Nov;155(11):1735-53
references.pmid: 20842391
references.citation: Am J Gastroenterol. 2008 Oct;103(10):2481-7
references.pmid: 18702647
references.citation: J Viral Hepat. 2009 Oct;16(10):716-23
references.pmid: 19302338
references.citation: J Gastroenterol Hepatol. 2015 May;30(5):879-84
references.pmid: 23808794
references.citation: Gastroenterology. 2006 May;130(6):1636-42
references.pmid: 16697727
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15669-74
references.pmid: 12441396
references.citation: J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S108-11
references.pmid: 17567457
references.citation: Hepatology. 2010 Sep;52(3):854-63
references.pmid: 20690192
references.citation: Am J Gastroenterol. 2002 Nov;97(11):2880-5
references.pmid: 12425563
references.citation: Atherosclerosis. 2012 Apr;221(2):496-502
references.pmid: 22385985
references.citation: Science. 1999 Jul 2;285(5424):110-3
references.pmid: 10390360
references.citation: J Biol Chem. 2014 Aug 1;289(31):21276-88
references.pmid: 24917668
references.citation: PLoS Pathog. 2012 Jan;8(1):e1002466
references.pmid: 22241992
references.citation: Aliment Pharmacol Ther. 2009 Jan;29(1):46-54
references.pmid: 18680550
references.citation: Hepatology. 2008 Aug;48(2):374-84
references.pmid: 18666256
references.citation: Mol Cell Proteomics. 2013 Mar;12(3):710-9
references.pmid: 23264353
references.citation: J Hepatol. 2008 Dec;49(6):1046-54
references.pmid: 18752865
references.citation: Nat Clin Pract Rheumatol. 2007 Dec;3(12):716-24
references.pmid: 18037931
references.citation: J Hepatol. 2012 Oct;57(4):867-73
references.pmid: 22732512
references.citation: J Hepatol. 2005 Dec;43(6):929-36
references.pmid: 16139921
references.citation: Aliment Pharmacol Ther. 2013 Jan;37(1):74-80
references.pmid: 23121166
references.citation: Hepatology. 2012 Jul;56(1):49-56
references.pmid: 22318926
references.citation: Aliment Pharmacol Ther. 2013 Mar;37(6):647-52
references.pmid: 23384408
references.citation: Dig Liver Dis. 2007 Sep;39 Suppl 1:S55-60
references.pmid: 17936225
references.citation: J Biol Chem. 2009 Nov 27;284(48):33466-74
references.pmid: 19808675
references.citation: Clin Gastroenterol Hepatol. 2013 Mar;11(3):311-7.e1
references.pmid: 23220171
references.citation: J Viral Hepat. 2012 Feb;19(2):e126-33
references.pmid: 22239510
references.citation: Trends Endocrinol Metab. 2010 Jan;21(1):33-40
references.pmid: 19854061
references.citation: J Hepatol. 2009 Mar;50(3):471-8
references.pmid: 19155083
references.citation: J Hepatol. 2011 Nov;55(5):963-71
references.pmid: 21354229
references.citation: Science. 2005 Jul 22;309(5734):623-6
references.pmid: 15947137
references.citation: Oncology. 2010 Jul;78 Suppl 1:24-30
references.pmid: 20616580
references.citation: Dig Dis. 2010;28(1):280-4
references.pmid: 20460924
references.citation: J Viral Hepat. 2006 Feb;13(2):73-80
references.pmid: 16436124
references.citation: Int J Cancer. 2008 Jan 1;122(1):124-31
references.pmid: 17764115
references.citation: Kardiologiia. 1991 Apr;31(4):25-8
references.pmid: 1829771
references.citation: Eur J Clin Invest. 2011 Aug;41(8):898-905
references.pmid: 21539538
references.citation: PLoS One. 2014;9(4):e94460
references.pmid: 24718268
references.citation: J Gastroenterol. 2013 Jan;48(1):93-100
references.pmid: 22678465
references.citation: Hepatology. 2007 Oct;46(4):1009-15
references.pmid: 17668875
references.citation: J Viral Hepat. 2007 Jan;14(1):29-35
references.pmid: 17212641
references.citation: Liver Int. 2011 Sep;31(8):1155-62
references.pmid: 21745292
references.citation: J Viral Hepat. 2012 Apr;19(4):271-7
references.pmid: 22404725
references.citation: Liver Int. 2008 Feb;28(2):271-7
references.pmid: 18028320
references.citation: BMC Genomics. 2008;9:109
references.pmid: 18307821
references.citation: Aliment Pharmacol Ther. 2009 Sep 1;30(5):444-51
references.pmid: 19493257
references.citation: Hepatology. 2009 Sep;50(3):957-69
references.pmid: 19585655
references.citation: Biochim Biophys Acta. 2015 Oct;1854(10 Pt B):1657-62
references.pmid: 25896387
references.citation: Arch Virol. 2014 May;159(5):1017-25
references.pmid: 24240483
references.citation: Hepatology. 2009 Mar;49(3):739-44
references.pmid: 19127513
references.citation: J Viral Hepat. 2012 Jul;19(7):465-72
references.pmid: 22676358
references.citation: J Hepatol. 2012;56 Suppl 1:S56-65
references.pmid: 22300466
references.citation: Am J Gastroenterol. 2008 Mar;103(3):605-14
references.pmid: 18190648
references.citation: Intern Med. 2013;52(15):1665-73
references.pmid: 23903497
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3805-9
references.pmid: 16484368
references.citation: J Virol. 2010 Jun;84(12):5936-46
references.pmid: 20357092
references.citation: Front Microbiol. 2012 Jan 10;2:278
references.pmid: 22291689
references.citation: Gastroenterology. 2002 Feb;122(2):366-75
references.pmid: 11832451
references.citation: Hepatology. 2008 Jun;47(6):2127-33
references.pmid: 18446789
references.citation: Am J Gastroenterol. 2005 Dec;100(12):2717-23
references.pmid: 16393225
references.citation: J Virol. 2012 Jun;86(11):6315-22
references.pmid: 22457523
references.citation: J Clin Invest. 2008 Feb;118(2):683-94
references.pmid: 18188449
references.citation: Viruses. 2012 Oct;4(10):2233-50
references.pmid: 23202462
references.citation: J Viral Hepat. 2014 Oct;21(10):706-15
references.pmid: 24304473
references.citation: J Hepatol. 2012 Mar;56(3):533-40
references.pmid: 22027575
references.citation: J Gastroenterol Hepatol. 2011 Jul;26(7):1182-8
references.pmid: 21410752
references.citation: J Hepatol. 2008 Jan;48(1):28-34
references.pmid: 17977612
references.citation: Virology. 2002 Jan 20;292(2):198-210
references.pmid: 11878923
references.citation: J Viral Hepat. 2013 Feb;20(2):77-84
references.pmid: 23301542
references.citation: Hepatology. 2006 Dec;44(6):1648-55
references.pmid: 17133473
references.citation: J Hepatol. 2003 Dec;39(6):1042-8
references.pmid: 14642624
references.citation: Curr Med Chem. 2012;19(8):1193-209
references.pmid: 22257055
references.citation: J Infect Dis. 2012 Aug 15;206(4):469-77
references.pmid: 22811301
references.citation: Nature. 2005 Aug 18;436(7053):933-8
references.pmid: 16107832
references.citation: Gastroenterology. 2008 Feb;134(2):416-23
references.pmid: 18164296
references.citation: World J Gastroenterol. 2005 Jun 14;11(22):3357-62
references.pmid: 15948239
references.citation: BMC Med Genet. 2012;13:82
references.pmid: 22978414
references.citation: PLoS One. 2014;9(8):e104783
references.pmid: 25122116
references.citation: Atherosclerosis. 2013 Nov;231(1):22-6
references.pmid: 24125405
references.citation: J Gastroenterol Hepatol. 2011 Mar;26(3):530-5
references.pmid: 21332548
references.citation: Liver Int. 2010 Sep;30(8):1131-6
references.pmid: 20536721
references.citation: Dig Dis Sci. 2009 Dec;54(12):2699-705
references.pmid: 19148751
references.citation: J Virol. 2014 Aug;88(15):8361-74
references.pmid: 24829353
references.citation: J Hepatol. 2009 Apr;50(4):712-8
references.pmid: 19231011
references.citation: PLoS Pathog. 2007 Aug 31;3(8):e108
references.pmid: 17784784
references.citation: Gastroenterology. 2012 May;142(6):1264-1273.e1
references.pmid: 22537432
references.citation: Viruses. 2013 Mar;5(3):954-80
references.pmid: 23518579
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2451-5
references.pmid: 1848704
references.citation: J Gastrointestin Liver Dis. 2012 Mar;21(1):59-65
references.pmid: 22457861
references.citation: Chang Gung Med J. 2011 Sep-Oct;34(5):487-95
references.pmid: 22035893
references.citation: Hepatology. 2014 Apr;59(4):1293-302
references.pmid: 24122848
references.citation: PLoS Pathog. 2012 Jan;8(1):e1002468
references.pmid: 22241994
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1200-5
references.pmid: 9037030
references.citation: FASEB J. 2002 Feb;16(2):185-94
references.pmid: 11818366
references.citation: Gut. 2007 Aug;56(8):1105-10
references.pmid: 16956918
references.citation: J Viral Hepat. 2008 Feb;15(2):129-36
references.pmid: 18184196
references.citation: Diabetes Res Clin Pract. 2007 Mar;75(3):320-6
references.pmid: 16919355
references.citation: Dig Dis Sci. 2012 Aug;57(8):2213-21
references.pmid: 22543885
references.citation: J Viral Hepat. 2012 Feb;19(2):e48-57
references.pmid: 22239526
references.citation: Aliment Pharmacol Ther. 2006 Aug 1;24(3):507-12
references.pmid: 16886916
references.citation: PPAR Res. 2009;2009:357204
references.pmid: 19343188
references.citation: Nat Med. 2005 Jul;11(7):791-6
references.pmid: 15951748
references.citation: Gut. 2010 Aug;59(8):1135-40
references.pmid: 20584782
references.citation: Hum Immunol. 2012 Apr;73(4):382-8
references.pmid: 22333691
references.citation: J Virol. 2015 Jul;89(13):6805-16
references.pmid: 25903345
references.citation: Obes Surg. 2005 May;15(5):692-9
references.pmid: 15946462
references.citation: Kaohsiung J Med Sci. 2009 Jun;25(6):299-305
references.pmid: 19560994
references.citation: J Virol. 2015 Apr;89(8):4092-101
references.pmid: 25673715
references.citation: Gastroenterology. 2012 Mar;142(3):644-653.e3
references.pmid: 22155365
references.citation: PLoS Pathog. 2010 Jan;6(1):e1000719
references.pmid: 20062526
references.citation: Am J Gastroenterol. 2003 Sep;98(9):2064-71
references.pmid: 14499789
references.citation: J Virol. 2010 Jan;84(1):666-70
references.pmid: 19846523
references.citation: Gut. 2005 Jul;54(7):1003-8
references.pmid: 15951550
references.citation: Clin Gastroenterol Hepatol. 2011 Aug;9(8):688-93
references.pmid: 21640198
references.citation: World J Gastroenterol. 2006 Nov 28;12(44):7075-80
references.pmid: 17131467
references.citation: Semin Liver Dis. 2006 May;26(2):153-61
references.pmid: 16673293
references.citation: World J Gastroenterol. 2007 Jul 7;13(25):3472-7
references.pmid: 17659694
references.citation: J Endocrinol Invest. 2013 Sep;36(8):600-5
references.pmid: 23449040