title: Metabolic factors and chronic hepatitis C: a complex interplay.
abstract: In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.
authors: Section of Gastroenterology, DiBiMIS, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. fsmacaluso@gmail.com
authors: Fabio Salvatore
authors: FS
authors: Macaluso
authors: Marcello
authors: M
authors: Maida
authors: Maria Giovanna
authors: MG
authors: Minissale
authors: Teresa
authors: T
authors: Li Vigni
authors: Simona
authors: S
authors: Attardo
authors: Emanuele
authors: E
authors: Orlando
authors: Salvatore
authors: S
authors: Petta
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012307:Risk Factors
references: Hepatology. 2005 May;41(5):995-1003
references: 15834927
references: Gastroenterology. 2003 Dec;125(6):1695-704
references: 14724822
references: Hepatology. 2010 Sep;52(3):864-74
references: 20568303
references: PLoS One. 2010 Jul 14;5(7):e11578
references: 20644649
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3739-44
references: 10523023
references: Hepatology. 2008 Jul;48(1):28-37
references: 18506842
references: Hepatology. 2006 Jan;43(1):64-71
references: 16374856
references: J Hepatol. 2012 Oct;57(4):897-909
references: 22634121
references: J Hepatol. 2008 Jun;48(6):993-9
references: 18395287
references: Dig Liver Dis. 2012 May;44(5):359-60
references: 22418268
references: Gut. 2003 Feb;52(2):288-92
references: 12524415
references: J Viral Hepat. 2002 Mar;9(2):114-22
references: 11876793
references: J Clin Epidemiol. 2001 Aug;54(8):823-9
references: 11470392
references: Gut. 2005 Jan;54(1):122-7
references: 15591516
references: Scand J Clin Lab Invest. 1986 Feb;46(1):63-70
references: 2869572
references: Antivir Ther. 2012;17(5):823-31
references: 22505587
references: Liver Int. 2012 Apr;32(4):635-43
references: 22151003
references: Nature. 2001 Dec 13;414(6865):782-7
references: 11742409
references: Hepatology. 2011 Apr;53(4):1118-26
references: 21480318
references: Hepatology. 2009 Mar;49(3):739-44
references: 19127513
references: Diabetes Care. 2010 Apr;33(4):920-2
references: 20067971
references: Antivir Ther. 2009;14(5):631-9
references: 19704165
references: Gastroenterology. 2009 Aug;137(2):549-57
references: 19445938
references: J Hepatol. 2013 Mar;58(3):467-72
references: 23183524
references: J Hepatol. 2010 Nov;53(5):827-33
references: 20728234
references: Aliment Pharmacol Ther. 2009 Sep 1;30(5):444-51
references: 19493257
references: J Clin Microbiol. 2007 Aug;45(8):2426-33
references: 17537941
references: Gastroenterology. 2007 May;132(5):1740-5
references: 17484871
references: Atherosclerosis. 2012 Apr;221(2):496-502
references: 22385985
references: Cancer. 2007 Jun 15;109(12):2490-6
references: 17487861
references: N Engl J Med. 2008 Oct 23;359(17):1811-21
references: 18946066
references: J Clin Virol. 2010 Jan;47(1):72-5
references: 19896417
references: Diabetes Care. 2013 Jan;36(1):150-6
references: 22933433
references: Dig Liver Dis. 2007 Sep;39 Suppl 1:S55-60
references: 17936225
references: Hepatology. 2012 May;55(5):1317-23
references: 22135089
references: J Gastroenterol Hepatol. 2003 Apr;18(4):386-92
references: 12653886
references: Gastroenterology. 2002 Feb;122(2):352-65
references: 11832450
references: Gastroenterology. 2004 Mar;126(3):840-8
references: 14988838
references: Am J Gastroenterol. 2008 May;103(5):1136-44
references: 18477344
references: Gut. 2010 Aug;59(8):1135-40
references: 20584782
references: Virol J. 2011 Oct 18;8:474
references: 22008087
references: Atherosclerosis. 2004 May;174(1):99-103
references: 15135257
references: Clin Gastroenterol Hepatol. 2013 Mar;11(3):311-7.e1
references: 23220171
references: Curr Diab Rep. 2003 Aug;3(4):279-88
references: 12866989
references: Lancet. 1997 Mar 22;349(9055):825-32
references: 9121257
references: Hepatology. 2004 Dec;40(6):1426-33
references: 15565616
references: Dig Liver Dis. 2002 Mar;34(3):204-11
references: 11990393
references: Hepatology. 1999 Apr;29(4):1215-9
references: 10094967
references: Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G987-95
references: 18772365
references: J Gastroenterol. 2013 Jan;48(1):93-100
references: 22678465
references: Gastroenterology. 2009 Sep;137(3):865-72
references: 19524579
references: Curr Pharm Des. 2010;16(6):741-52
references: 20388084
references: J Hepatol. 2011 May;54(5):887-93
references: 21145801
references: J Hepatol. 2009 Dec;51(6):984-90
references: 19695729
references: Gut. 2006 Apr;55(4):529-35
references: 16299039
references: Am J Clin Nutr. 2004 Dec;80(6 Suppl):1717S-20S
references: 15585793
references: Hepatology. 2012 Feb;55(2):336-42
references: 21932415
references: Obesity (Silver Spring). 2012 Mar;20(3):689-91
references: 21901024
references: Hepatology. 1999 Jun;29(6):1743-51
references: 10347117
references: J Viral Hepat. 2012 Jul;19(7):465-72
references: 22676358
references: Nature. 2006 Dec 14;444(7121):881-7
references: 17167477
references: Hepatology. 2005 Jul;42(1):113-20
references: 15920717
references: Gut. 2007 Aug;56(8):1105-10
references: 16956918
references: Eur J Epidemiol. 1993 May;9(3):293-7
references: 8104822
references: Hepatology. 2010 Sep;52(3):854-63
references: 20690192
references: Lancet. 2002 Jan 12;359(9301):133-5
references: 11809259
references: PLoS One. 2012;7(9):e44624
references: 22970270
references: Hepatology. 2010 Apr;51(4):1158-67
references: 20162613
references: Hepatology. 2009 Sep;50(3):697-706
references: 19582803
references: J Viral Hepat. 2013 Jul;20(7):486-93
references: 23730842
references: Dig Liver Dis. 2012 May;44(5):406-12
references: 22245505
references: Hepatology. 2011 Mar;53(3):791-9
references: 21319195
references: Gastroenterology. 2005 Jan;128(1):24-32
references: 15633120
references: J Med Virol. 2008 Apr;80(4):628-31
references: 18297716
references: J Clin Invest. 2004 Jul;114(2):147-52
references: 15254578
references: Hepatology. 2008 Jun;47(6):2127-33
references: 18446789
references: Clin Chem Lab Med. 2010 Feb;48(2):175-80
references: 19961393
references: Gastroenterology. 2006 May;130(6):1636-42
references: 16697727
references: Nat Immunol. 2010 Apr;11(4):344-9
references: 20208539
references: Hepatology. 2003 Jul;38(1):75-85
references: 12829989
references: Hepatology. 2007 Jan;45(1):80-7
references: 17187406
references: Hepatology. 2010 Aug;52(2):578-89
references: 20683957
references: Circ J. 2003 Jan;67(1):26-30
references: 12520147
references: QJM. 2002 Dec;95(12):787-96
references: 12454321
references: J Hepatol. 2008 Jan;48(1):28-34
references: 17977612
references: Gastroenterology. 2008 Feb;134(2):416-23
references: 18164296
references: Curr Opin Rheumatol. 2009 Mar;21(2):132-7
references: 19339923
references: Menopause. 2009 Mar-Apr;16(2):401-6
references: 19002016
references: Acta Gastroenterol Belg. 2010 Jan-Mar;73(1):12-7
references: 20458845
references: Hepatology. 1997 Mar;25(3):735-9
references: 9049227
references: World J Gastroenterol. 2011 Dec 21;17(47):5184-90
references: 22215943
references: Stroke. 2010 Dec;41(12):2894-900
references: 20966408
references: Gastroenterology. 2011 Jun;140(7):1961-9
references: 21376050
references: Dig Dis. 2010;28(1):280-4
references: 20460924
references: Dig Liver Dis. 2011 May;43(5):404-10
references: 21324757
references: Arch Intern Med. 2006 Jun 12;166(11):1190-5
references: 16772246
references: Aliment Pharmacol Ther. 2011 Oct;34(7):757-66
references: 21790685
references: Gut. 2010 Sep;59(9):1279-87
references: 20660700
references: Hepatology. 2001 Jun;33(6):1358-64
references: 11391523
references: Hepatology. 2008 Sep;48(3):723-31
references: 18688878
references: J Clin Invest. 2008 Feb;118(2):683-94
references: 18188449
references: World J Gastroenterol. 2006 Nov 14;12(42):6756-65
references: 17106922
references: Int J Obes (Lond). 2013 Apr;37(4):532-9
references: 22890489
references: Hepatology. 2010 Nov;52(5):1543-52
references: 20799355
references: Nat Genet. 2013 Feb;45(2):164-71
references: 23291588
references: Hepatology. 2009 Oct;50(4):1030-7
references: 19787818
references: Hepatology. 2010 Jun;51(6):1961-71
references: 20301112
references: J Clin Gastroenterol. 2013 Jul;47(6):545-52
references: 23426443
references: Hepatology. 2008 Jul;48(1):16-27
references: 18570290
references: Aliment Pharmacol Ther. 2013 Mar;37(6):647-52
references: 23384408
references: Diabetes Obes Metab. 2006 Nov;8(6):698-702
references: 17026495
references: N Engl J Med. 2009 Aug 6;361(6):580-93
references: 19625712
references: J Hepatol. 2004 Mar;40(3):484-90
references: 15123364
references: Hepatology. 2005 Nov;42(5):987-1000
references: 16250043
references: Virology. 1996 Aug 1;222(1):51-63
references: 8806487
references: Eur J Gastroenterol Hepatol. 2006 Mar;18(3):233-7
references: 16462535
references: Hepatology. 2011 Aug;54(2):484-94
references: 21538438
references: World J Gastroenterol. 2012 Feb 28;18(8):800-5
references: 22371640
references: Metabolism. 2011 Jun;60(6):860-6
references: 20863537
references: Gastroenterology. 2004 Feb;126(2):586-97
references: 14762795
references: Liver Int. 2012 Oct;32(9):1443-50
references: 22764879
references: Liver Int. 2009 Feb;29(2):248-52
references: 18662278
references: Am J Clin Nutr. 2004 Apr;79(4):537-43
references: 15051594
references: J Viral Hepat. 2012 Sep;19(9):640-9
references: 22863268
references: Hepatology. 2008 Aug;48(2):449-57
references: 18627003
references: Gastroenterology. 2011 Mar;140(3):818-29
references: 21167831
references: Hepatology. 2004 May;39(5):1230-8
references: 15122751
references: Liver Int. 2009 Jan;29 Suppl 1:74-81
references: 19207969
references: Gastroenterology. 2012 Sep;143(3):608-618.e5
references: 22626609
references: J Gastroenterol. 2005 Jun;40(6):617-24
references: 16007396
references: Hepatology. 2000 Mar;31(3):751-5
references: 10706568
references: Cytokine. 2013 Jan;61(1):266-74
references: 23141142
references: Dig Liver Dis. 2012 May;44(5):419-25
references: 22277808
references: Hepatology. 2010 Apr;51(4):1209-17
references: 20373368
references: Hepatology. 2005 Dec;42(6):1339-48
references: 16317688
references: J Hepatol. 2005 May;42(5):744-51
references: 15826725
references: Hepatology. 2010 Jun;51(6):1904-11
references: 20235331
references: J Gen Virol. 1997 Jul;78 ( Pt 7):1527-31
references: 9225025
references: Gastroenterology. 2005 Mar;128(3):636-41
references: 15765399
references: Hepatology. 2005 Jan;41(1):82-7
references: 15690484
references: Gut. 2012 Oct;61(10):1473-80
references: 22387529
references: J Hepatol. 2011 Dec;55(6):1187-94
references: 21703195
references: Gastroenterology. 2008 Jul;135(1):111-21
references: 18505690
references: Gastroenterology. 2007 May;132(6):2169-80
references: 17498510
references: Hepatology. 2009 Jan;49(1):195-203
references: 19065558
references: J Infect Dis. 2012 Aug 15;206(4):469-77
references: 22811301
references: Gut. 2011 Mar;60(3):378-86
references: 20940285
references: Gastroenterology. 2002 Feb;122(2):366-75
references: 11832451
references: J Hepatol. 2009 May;50(5):1029-34
references: 19299029
references: Diabetes Care. 2006 Mar;29(3):722-4
references: 16505539
references: Lancet. 2010 Jul 17;376(9736):180-8
references: 20541252
references: J Hepatol. 2012;56 Suppl 1:S56-65
references: 22300466
references: J Hepatol. 2007 Jun;46(6):1126-32
references: 17335930
references: J Hepatol. 2008 Nov;49(5):711-7
references: 18619698
references: Gut Liver. 2010 Sep;4(3):378-83
references: 20981217
references: Hepatology. 2013 Dec;58(6):1897-906
references: 24382638
references: Liver Int. 2008 Feb;28(2):257-63
references: 17900242
references: Hepatology. 2009 Nov;50(5):1360-9
references: 19676128
references: J Hepatol. 2006 Feb;44(2):253-61
references: 16364488
references: Ann Nutr Metab. 2009;55(4):351-7
references: 19851063
references: Gut. 2010 Oct;59(10):1410-5
references: 20660697
references: J Hepatol. 2007 May;46(5):927-34
references: 17391799
references: Gastroenterology. 2006 Aug;131(2):470-7
references: 16890601