Internal and Emergency Medicine

, Volume 3, Issue 2, pp 99–108 | Cite as

Dysmetabolic changes associated with HCV: a distinct syndrome?

  • Amedeo LonardoEmail author
  • Paola Loria
  • Nicola Carulli
IM - Review


Although not associated with the metabolic syndrome, HCV is linked with impaired insulin signalling, insulin resistance, hypocholesterolemia and steatosis which represent a distinct HCV-associated dysmetabolic syndrome. Insulin resistance affects the development of diabetes, fibrosis, impaired response to antivirals and perhaps hepatocellular carcinoma risk. HCV infection is associated with hypocholesterolemia and steatosis reversible after sustained virologic response. A “viral”, and a “metabolic” steatosis exist as function of viral genotypes. Little is known about the possible role of HCV in further components of the metabolic syndrome such as atherosclerosis, obesity, arterial hypertension, hyperuricemia and thrombotic risk factors.


Fibrosis Ferritin Hypobetalipoproteinemia HCV Hepatocellular carcinoma Insulin resistance Interferon Metabolic syndrome Ribavirin Steatosis Type 2 diabetes 


  1. 1.
    Wong T, Lee SS (2006) Hepatitis C: a review for primary care physicians. CMAJ 174:649–659PubMedGoogle Scholar
  2. 2.
    Anonimymous (1999) EASL International Consensus Conference on Hepatitis C Paris, 26–27 February 1999 Consensus Statement Conference. J Hepatol 31:3–8Google Scholar
  3. 3.
    Wasley A, Alter MJ (2000) Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis20:1–16Google Scholar
  4. 4.
    Ansaldi F, Bruzzone B, Salmaso S, Rota MC, Durando P, Gasparini R, Icardi G (2005) Different seroprevalence and molecular epidemiology patterns of hepatitis C virus infection in Italy. J Med Virol 76:327–332PubMedGoogle Scholar
  5. 5.
    Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH (2000) Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 132:296–305PubMedGoogle Scholar
  6. 6.
    Sene D, Limal N, Cacoub P (2004) Hepatitis C virus-associated extrahepatic manifestations: a review. Metab Brain Dis 19:357–381PubMedGoogle Scholar
  7. 7.
    Koike K, Moriya K (2005) Metabolic aspects of hepatitis C viral infection: steatohepatitis resembling but distinct from NASH. J Gastroenterol 40:329–336PubMedGoogle Scholar
  8. 8.
    Bach N, Thung SN, Schaffner F (1992) The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 15:572–577PubMedGoogle Scholar
  9. 9.
    Loria P, Lonardo A, Carulli L, Verrone AM, Ricchi M, Lombardini S, Rudilosso A, Ballestri S, Carulli N (2005) Review article: the metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 22(Suppl 2):31–36PubMedGoogle Scholar
  10. 10.
    Reisin E, Alpert MA (2005) Definition of the metabolic syndrome: current proposals and controversies. Am J Med Sci 330:269–272PubMedGoogle Scholar
  11. 11.
    Zambon A, Pauletto P, Crepaldi G (2005) Review article: the metabolic syndrome—a chronic cardiovascular inflammatory condition. Aliment Pharmacol Ther 22(Suppl 2):20–23PubMedGoogle Scholar
  12. 12.
    Ahmed I, Goldstein BJ (2006) Cardiovascular risk in the spectrum of type 2 diabetes mellitus. Mt Sinai J Med 73:759–768PubMedGoogle Scholar
  13. 13.
    Cowey S, Hardy RW (2006) The metabolic syndrome: a high-risk state for cancer? Am J Pathol 169:1505–1522PubMedGoogle Scholar
  14. 14.
    Choi J, Ou JH (2006) Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am J Physiol Gastrointest Liver Physiol 290:G847–G851PubMedGoogle Scholar
  15. 15.
    Diaz JM, Sainz Z, Guirado LL, Ortiz-Herbener F, Picazo M, Garcia-Camin R, Palou J, Alcaraz A, Sola R (2003) Risk factors for cardiovascular disease after renal transplantation. Transplant Proc 35:1722–1724PubMedGoogle Scholar
  16. 16.
    Seeff LB (1997) The natural history of chronic hepatitis C virus infection. Clin Liver Dis 1:587–602PubMedGoogle Scholar
  17. 17.
    Ratziu V, Munteanu M, Charlotte F, Bonyhay L, Poynard T (2003) LIDO Study Group. Fibrogenic impact of high serum glucose in chronic hepatitis C. J Hepatol 39:1049–1055PubMedGoogle Scholar
  18. 18.
    Lonardo A, Loria P, Adinolfi LE, Carulli N, Ruggiero G (2006) Hepatitis C and steatosis: a reappraisal. J Viral Hepat 13:73–80PubMedGoogle Scholar
  19. 19.
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G (2001) Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33:1358–1364PubMedGoogle Scholar
  20. 20.
    Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, Younossi Z, Albrecht J (2003) Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38:75–85PubMedGoogle Scholar
  21. 21.
    Lonardo A, Lombardini S, Scaglioni F, Carulli L, Ricchi M, Ganazzi D, Adinolfi LE, Ruggiero G, Carulli N, Loria P (2006) Hepatic steatosis and insulin resistance: does etiology make a difference? J Hepatol 44:190–196PubMedGoogle Scholar
  22. 22.
    Shaheen M, Echeverry D, Oblad MG, Montoya MI, Teklehaimanot S, Akhtar AJ (2007) Hepatitis C, metabolic syndrome, and inflammatory markers: results from the Third National Health and Nutrition Examination Survey [NHANES III]. Diabetes Res Clin Pract 75:320–326PubMedGoogle Scholar
  23. 23.
    Lin TJ, Liao LY, Lin SY, Lin CL, Chang TA (2006) Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C. World J Gastroenterol 12:4897–4901PubMedGoogle Scholar
  24. 24.
    Loria P, Lonardo A, Carulli N (2005) Should nonalcoholic fatty liver disease be renamed? Dig Dis 23:72–82PubMedGoogle Scholar
  25. 25.
    Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R (2007) NAFLD and hyperinsulinemia are major determinants of serum ferritin levels. J Hepatol 46:700–707PubMedGoogle Scholar
  26. 26.
    Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126:840–848PubMedGoogle Scholar
  27. 27.
    Delgado-Borrego A, Casson D, Schoenfeld D, Somsouk M, Terella A, Jordan SH, Bhan A, Baid S, Cosimi AB, Pascual M, Chung RT (2004) Hepatitis C virus is independently associated with increased insulin resistance after liver transplantation. Transplantation 77:703–710PubMedGoogle Scholar
  28. 28.
    Romero-Gomez M (2006) Hepatitis C and insulin resistance: steatosis, fibrosis and non-response. Rev Esp Enferm Dig 98:605–615PubMedCrossRefGoogle Scholar
  29. 29.
    Negro F (2006) Mechanisms and significance of liver steatosis in hepatitis C virus infection. World J Gastroenterol 12:6756–6765PubMedGoogle Scholar
  30. 30.
    Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, Taniguchi E, Kumemura H, Hanada S, Maeyama M, Baba S, Koga H, Kumashiro R, Ueno T, Ogata H,Yoshimura A, Sata M (2004) Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol 165:1499–1508PubMedGoogle Scholar
  31. 31.
    Durante-Mangoni E, Zampino R, Marrone A, Tripodi MF, Rinaldi L, Restivo L, Cioffi M, Ruggiero G, Adinolfi LE (2006) Hepatic steatosis and insulin resistance are associated with serum imbalance of adiponectin/tumour necrosis factor-alpha in chronic hepatitis C patients. Aliment Pharmacol Ther 24:1349–1357PubMedGoogle Scholar
  32. 32.
    Aytug S, Reich D, Sapiro LE, Bernstein D, Begum N (2003) Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology 38:1384–1392PubMedGoogle Scholar
  33. 33.
    de Gottardi A, Pazienza V, Pugnale P, Bruttin F, Rubbia-Brandt L, Juge-Aubry CE, Meier CA, Hadengue A, Negro F (2006) Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection. Aliment Pharmacol Ther 23:107–114PubMedGoogle Scholar
  34. 34.
    Lonardo A, Carulli N and Loria P (2007) HCV and diabetes. A 2 question-based reappraisal. Dig Liver Dis. doi: 10.1016/j.dld.2007.05.005
  35. 35.
    Walsh MJ, Jonsson JR, Richardson MM, Lipka GM, Purdie DM, Clouston AD, Powell EE (2006) Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1. Gut 55:529–535. Epub 18 Nov 2005PubMedGoogle Scholar
  36. 36.
    Naunyn B (1898) Glykosurie und Diabetes durch experimentelle Insulte und Krankheiten der Leber. In: Nothnagel E (ed) Der Diabetes mellitus in Handbuch. Spez Path Ther Bd 7. Holder A, Wien, pp 38–49Google Scholar
  37. 37.
    Allison ME, Wreghitt T, Palmer CR, Alexander GJ (1994) Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol 21:1135–1139PubMedGoogle Scholar
  38. 38.
    Ozyilkan E, Arslan M (1996) Increased prevalence of diabetes mellitus in patients with chronic hepatitis C virus infection. Am J Gastroenterol 91:1480–1481PubMedGoogle Scholar
  39. 39.
    Del Olmo JA, Serra MA, Rodrigo JM (1996) Liver cirrhosis and diabetes mellitus. J Hepatol 24:645PubMedGoogle Scholar
  40. 40.
    Grimbert S, Valensi P, Levy-Marchal C, Perret G, Richardet JP, Raffoux C, Trinchet JC, Beaugrand M (1996) High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study. Gastroenterol Clin Biol 20:544–548PubMedGoogle Scholar
  41. 41.
    Fraser GM, Harman I, Meller N, Niv Y, Porath A (1996) Diabetes mellitus is associated with chronic hepatitis C but not chronic hepatitis B infection. Isr J Med Sci 32:526–530PubMedGoogle Scholar
  42. 42.
    Mangia A, Schiavone G, Lezzi G, Marmo R, Bruno F, Villani MR, Cascavilla I, Fantasia L, Andriulli A (1998) HCV and diabetes mellitus: evidence for a negative association. Am J Gastroenterol 93:2363–2367PubMedGoogle Scholar
  43. 43.
    Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, Guo L, Jacob S, Regenstein FG, Zimmerman R, Everhart JE, Wasserfall C, Maclaren NK, Perrillo RP (1999) Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 29:328–333PubMedGoogle Scholar
  44. 44.
    Caronia S, Taylor K, Pagliaro L, Carr C, Palazzo U, Petrik J, O’Rahilly S, Shore S, Tom BD, Alexander GJ (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063PubMedGoogle Scholar
  45. 45.
    Macedo G, Ribeiro T (1999) Cirrhosis and diabetes: C, the difference. Am J Gastroenterol 94:3088–3089PubMedGoogle Scholar
  46. 46.
    Labropoulou-Karatza C, Goritsas C, Fragopanagou H, Repandi M, Matsouka P, Alexandrides T (1999) High prevalence of diabetes mellitus among adult beta-thalassaemic patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 11:1033–1036PubMedGoogle Scholar
  47. 47.
    Knobler H, Schihmanter R, Zifroni A, Fenakel G, Schattner A (2000) Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection. Mayo Clin Proc 75:355–359PubMedCrossRefGoogle Scholar
  48. 48.
    Zein NN, Abdulkarim AS, Wiesner RH, Egan KS, Persing DH (2000) Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease. J Hepatol 32:209–217PubMedGoogle Scholar
  49. 49.
    Arao M, Murase K, Kusakabe A, Yoshioka K, Fukuzawa Y, Ishikawa T, Tagaya T, Yamanouchi K, Ichimiya H, Sameshima Y, Kakumu S (2003) Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus. J Gastroenterol 38:355–360PubMedGoogle Scholar
  50. 50.
    Wang CS, Wang ST, Yao WJ, Chang TT, Chou P (2003) Community-based study of hepatitis C virus infection and type 2 diabetes: an association affected by age and hepatitis severity status. Am J Epidemiol 158:1154–1160PubMedGoogle Scholar
  51. 51.
    Lecube A, Hernandez C, Genesca J, Esteban JI, Jardi R, Simo R (2004) High prevalence of glucose abnormalities in patients with hepatitis C virus infection. Diabetes Care 27:1171–1175PubMedGoogle Scholar
  52. 52.
    Kwon SY, Kim SS, Kwon OS, Kwon KA, Chung MG, Park DK, Kim YS, Koo YS, Kim YK, Choi DJ, Kim JH (2005) Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus. Diabet Med 22:1530–1535PubMedGoogle Scholar
  53. 53.
    Wilson C (2004) Hepatitis C infection and type 2 diabetes in American-Indian women. Diabetes Care 27:2116–2119PubMedGoogle Scholar
  54. 54.
    Alavian SM, Hajarizadeh B, Nematizadeh F, Larijani B (2004) Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease. BMC Endocr Disord 4:4PubMedGoogle Scholar
  55. 55.
    Antonelli A, Ferri C, Fallahi P, Sebastiani M, Nesti C, Barani L, Barale R, Ferrannini E (2004) Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients. Rheumatology (Oxford) 43:238–240Google Scholar
  56. 56.
    Papatheodoridis GV, Chrysanthos N, Savvas S, Sevastianos V, Kafiri G, Petraki K, Manesis EK (2006) Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis. J Viral Hepat 13:303–310PubMedGoogle Scholar
  57. 57.
    Antonelli A, Ferri C, Fallahi P, Pampana A, Ferrari SM, Goglia F, Ferrannini (2005) Hepatitis C virus infection: evidence for an association with type 2 diabetes. Diabetes Care 28:2548–2550PubMedGoogle Scholar
  58. 58.
    Zein CO, Levy C, Basu A, Zein NN (2005) Chronic hepatitis C and type II diabetes mellitus: a prospective cross-sectional study. Am J Gastroenterol 100:48–55PubMedGoogle Scholar
  59. 59.
    Zhao P, Wang JB, Jiao J (2006) Investigation on the incidence of diabetes in chronic hepatitis C patients and their HCV genotypes. Zhonghua Gan Zang Bing Za Zhi 14:86–88PubMedGoogle Scholar
  60. 60.
    Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133:592–599PubMedGoogle Scholar
  61. 61.
    Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, Szklo M, Thomas DL (2003) Hepatitis C virus infection and incident type 2 diabetes. Hepatology 38:50–56PubMedGoogle Scholar
  62. 62.
    El-Serag HB, Hampel H, Yeh C, Rabeneck L (2002) Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology 36:1439–1445PubMedGoogle Scholar
  63. 63.
    Gray H, Wreghitt T, Stratton IM, Alexander GJ, Turner RC, O’Rahilly S (1995) High Prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests. Diabet Med 12:244–249PubMedCrossRefGoogle Scholar
  64. 64.
    Simo R, Hernandez C, Genesca J, Jardi R, Mesa J (1996) High prevalence of hepatitis C virus infection in diabetic patients. Diabetes Care 19:998–1000PubMedGoogle Scholar
  65. 65.
    Soma J, Saito T, Taguma Y, Chiba S, Sato H, Sugimura K et al (2000) High Prevalence and adverse effects of hepatitis C virus infection in type II diabetic-related nephropathy. J Am Soc Nephrol 11:690–699PubMedGoogle Scholar
  66. 66.
    Sotiropoulos A, Peppas TA, Skliros E, Apostolou O, Kotsini V, Pappas SI (1999) Low prevalence of hepatitis C virus infection in Greek diabetic patients. Diab Med 16:250–252Google Scholar
  67. 67.
    Balogun WO, Adeleyde JO, Akinklade KS, Kuti M, Otegbayoe JA (2006) Low prevalence of hepatitis-C viral seropositivity among patients with type-2 diabetes mellitus in a tertiary hospital. J Natl Med Assoc 98:1805–1808PubMedGoogle Scholar
  68. 68.
    Behrendt CE, Ruiz RB (2006) Hyperglycemia among persons with hepatitis C: not the classical diabetic phenotype. Diabetes Res Clin Pract 71:68–74PubMedGoogle Scholar
  69. 69.
    Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L (2005) Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 54:1003–1008PubMedGoogle Scholar
  70. 70.
    Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, George J (2006) Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis. Hepatology 44:1648–1655PubMedGoogle Scholar
  71. 71.
    Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J (2005) Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 128:636–641PubMedGoogle Scholar
  72. 72.
    D’Souza R, Sabin CA, Foster GR (2005) Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am J Gastroenterol 100:1509–1515PubMedGoogle Scholar
  73. 73.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (2005) Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54:533–539PubMedGoogle Scholar
  74. 74.
    Trombetta M, Spiazzi G, Zoppini G, Muggeo M (2005) Review article: type 2 diabetes and chronic liver disease in the Verona diabetes study. Aliment Pharmacol Ther 22(Suppl 2):24–27PubMedGoogle Scholar
  75. 75.
    Levrero M (2006) Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene 25:3834–3847PubMedGoogle Scholar
  76. 76.
    Vollenweider P (2003) Insulin resistant states and insulin signaling. Clin Chem Lab Med 41:1107–1119PubMedGoogle Scholar
  77. 77.
    Chang CK, Ulrich CM (2003) Hyperinsulinaemia and hyperglycaemia: possible risk factors of colorectal cancer among diabetic patients. Diabetologia 46:595–607PubMedGoogle Scholar
  78. 78.
    Thomssen R, Bonk S, Propfe C, Heermann KH, Kochel HG, Uy A (1992) Association of hepatitis C virus in human sera with beta-lipoprotein. Med Microbiol Immunol (Berl) 181:293–300Google Scholar
  79. 79.
    Schettler V, Monazahian M, Wieland E, Ramadori G, Grunewald RW, Thomssen R, Muller GA (2001) Reduction of hepatitis C virus load by H.E.L.P.-LDL apheresis. Eur J Clin Invest 31:154–155PubMedGoogle Scholar
  80. 80.
    Diedrich G (2006) How does hepatitis C virus enter cells? FEBS J 273:3871–3885PubMedGoogle Scholar
  81. 81.
    Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX (1999) Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 96:12766–12771PubMedGoogle Scholar
  82. 82.
    Gopal K, Johnson TC, Gopal S, Walfish A, Bang CT, Suwandhi P, Pena-Sahdala HN, Clain DJ, Bodenheimer HC Jr, Min AD (2006) Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment. Hepatology 44:335–340PubMedGoogle Scholar
  83. 83.
    Carre D, Boucher E, Turlin B, Guyader D, Brissot P, Deugnier Y (1994) [Decrease of cholesterolemia and apolipoprotein B in chronic viral hepatitis C with massive steatosis]. Gastroenterol Clin Biol 18:899–900PubMedGoogle Scholar
  84. 84.
    Maggi G, Bottelli R, Gola D, Perricone G, Posca M, Zavaglia C, Ideo G (1996) Serum cholesterol and chronic hepatitis C. Ital J Gastroenterol 28:436–440PubMedGoogle Scholar
  85. 85.
    Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R (2001) Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 34:428–434PubMedGoogle Scholar
  86. 86.
    Hofer H, Bankl HC, Wrba F, Steindl-Munda P, Peck-Radosavljevic M, Osterreicher C, Mueller C, Gangl A, Ferenci P (2002) Hepatocellular fat accumulation and low serum cholesterol in patients infected with HCV-3a. Am J Gastroenterol 97:2880–2885PubMedGoogle Scholar
  87. 87.
    Fernandez-Rodriguez CM, Lopez-Serrano P, Alonso S, Gutierrez ML, Lledo JL, Perez-Calle JL, Temino R, Cacho G, Nevado M, Casas ML, Gasalla JM, Bonet B (2006) Long-term reversal of hypocholesterolaemia in patients with chronic hepatitis C is related to sustained viral response and viral genotype. Aliment Pharmacol Ther 24:507–512PubMedGoogle Scholar
  88. 88.
    Hui JM, Kench J, Farrell GC, Lin R, Samarasinghe D, Liddle C, Byth K, George J (2002) Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection. J Gastroenterol Hepatol 17:873–881PubMedGoogle Scholar
  89. 89.
    Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2007) Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol 46:403–410PubMedGoogle Scholar
  90. 90.
    Mirandola S, Realdon S, Iqbal J, Gerotto M, Dal Pero F, Bortoletto G, Marcolongo M, Vario A, Datz C, Hussain MM, Alberti A (2006) Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis. Gastroenterology 130:1661–1669PubMedGoogle Scholar
  91. 91.
    Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N (2006) Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 44:117–125PubMedGoogle Scholar
  92. 92.
    Brown MS, Goldstein JL (1981) Lowering plasma cholesterol by raising LDL receptors. N Engl J Med 305:515–517PubMedCrossRefGoogle Scholar
  93. 93.
    Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, Thomssen R (1999) Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 57:223–229PubMedGoogle Scholar
  94. 94.
    Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP (2004) Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 126:586–597PubMedGoogle Scholar
  95. 95.
    Lonardo A, Loria P, Bertolotti M., Carulli N (2007) Statins and HCV: a complex issue. Hepatology 45:257PubMedGoogle Scholar
  96. 96.
    Kiechl S, Egger G, Mayr M, Wiedermann CJ, Bonora E, Oberhollenzer F, Muggeo M, Xu Q, Wick G, Poewe W, Willeit J (2001) Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation 103:1064–1070PubMedGoogle Scholar
  97. 97.
    Bilora F, Rinaldi R, Boccioletti V, Petrobelli F, Girolami A (2002) Chronic viral hepatitis: a prospective factor against atherosclerosis. A study with echo-color Doppler of the carotid and femoral arteries and the abdominal aorta. Gastroenterol Clin Biol 26:1001–1004PubMedGoogle Scholar
  98. 98.
    Ishizaka N, Ishizaka Y, Takahashi E, Tooda E, Hashimoto H, Nagai R, Yamakado M (2002) Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet 359:133–135PubMedGoogle Scholar
  99. 99.
    Ishizaka Y, Ishizaka N, Takahashi E, Unuma T, Tooda E, Hashimoto H, Nagai R, Yamakado M (2003) Association between hepatitis C virus core protein and carotid atherosclerosis. Circ J 67:26–30PubMedGoogle Scholar
  100. 100.
    Vassalle C, Masini S, Bianchi F, Zucchelli GC (2004) Evidence for association between hepatitis C virus seropositivity and coronary artery disease. Heart 90:565–566PubMedGoogle Scholar
  101. 101.
    Haji SA, Starling RC, Avery RK, Mawhorter S, Tuzcu EM, Schoenhagen P, Cook DJ, Ratliff NB, McCarthy PM, Young JB, Yamani MH (2004) Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation. J Heart Lung Transplant 23:277–283PubMedGoogle Scholar
  102. 102.
    Volzke H, Schwahn C, Wolff B, Mentel R, Robinson DM, Kleine V, Felix SB, John U (2004) Hepatitis B and C virus infection and the risk of atherosclerosis in a general population. Atherosclerosis 174:99–103PubMedGoogle Scholar
  103. 103.
    Arcari CM, Nelson KE, Netski DM, Nieto FJ, Gaydos CA (2006) No association between hepatitis C virus seropositivity and acute myocardial infarction. Clin Infect Dis 43:e53–e56PubMedGoogle Scholar
  104. 104.
    Sawayama Y, Okada K, Maeda S, Ohnishi H, Furusyo N, Hayashi J (2006) Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy. Fukuoka Igaku Zasshi 97:245–255PubMedGoogle Scholar
  105. 105.
    Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C (2007) Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol 46:1126–1132PubMedGoogle Scholar
  106. 106.
    Liao KF, Peng CY, Lai SW, Chang WL, Hsu NY (2006) Descriptive epidemiology of hepatitis C virus among male heroin abusers in Taiwan. South Med J 99:348–351PubMedGoogle Scholar
  107. 107.
    Marchesini G, Ronchi M, Forlani G, Bugianesi E, Bianchi G, Fabbri A, Zoli M, Melchionda N (1999) Cardiovascular disease in cirrhosis—a point-prevalence study in relation to glucose tolerance. Am J Gastroenterol 94:655–662PubMedGoogle Scholar
  108. 108.
    Palomo I, Alarcon M, Moore-Carrasco R, Argiles JM (2006) Hemostasis alterations in metabolic syndrome. Int J Mol Med 18:969–974PubMedGoogle Scholar
  109. 109.
    Mato JM, Lu SC (2005) Homocysteine, the bad thiol. Hepatology 41:976–979PubMedGoogle Scholar
  110. 110.
    Adinolfi LE, Ingrosso D, Cesaro G, Cimmino A, D’Anto M, Capasso R, Zappia V, Ruggiero G (2005) Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology 41:995–1003PubMedGoogle Scholar
  111. 111.
    Ratziu V, Trabut JB, Poynard T (2004) Fat, diabetes, and liver injury in chronic hepatitis C. Curr Gastroenterol Rep 6:22–29PubMedGoogle Scholar
  112. 112.
    Wisniewska-Ligier M, Wozniakowska-Gesicka T, Kups J, Sulat-Syncerek D (2006) Lipid metabolism in children with chronic hepatitis C, A preliminary report. Hepatogastroenterology 53:887–891PubMedGoogle Scholar
  113. 113.
    Hu KQ, Kyulo NL, Esrailian E, Thompson K, Chase R, Hillebrand DJ, Runyon BA (2004) Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States. J Hepatol 40:147–154PubMedGoogle Scholar
  114. 114.
    Solis-Herruzo JA, Perez-Carreras M, Rivas E, Fernandez-Vazquez I, Garfia C, Bernardos E, Castellano G, Colina F (2005) Factors associated with the presence of nonalcoholic steatohepatitis in patients with chronic hepatitis C. Am J Gastroenterol 100:1091–1098PubMedGoogle Scholar
  115. 115.
    Romero-Gomez M, Castellano-Megias VM, Grande L, Irles JA, Cruz M, Nogales MC, Alcon JC, Robles A (2003) Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C. Am J Gastroenterol 98:1135–1141PubMedGoogle Scholar
  116. 116.
    McCullough AJ (2003) Obesity and its nurturing effect on hepatitis C. Hepatology 38:557–559PubMedGoogle Scholar
  117. 117.
    Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, Opolon P (1999) Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum 42:2204–2212PubMedGoogle Scholar
  118. 118.
    Poynard T, Cacoub P, Ratziu V, Myers RP, Dezailles MH, Mercadier A, Ghillani P, Charlotte F, Piette JC, Moussalli J (2002) Multivirc group. Fatigue in patients with chronic hepatitis C. J Viral Hepat 9:295–303PubMedGoogle Scholar
  119. 119.
    Tarantino G, Conca P, Sorrentino P, Ariello M (2006) Metabolic factors involved in the therapeutic response of patients with hepatitis C virus-related chronic hepatitis. J Gastroenterol Hepatol 21:1266–1268PubMedGoogle Scholar
  120. 120.
    Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS (2006) Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 55:1293–1301PubMedGoogle Scholar
  121. 121.
    Grassi A, Ballardini G, Susca M, Bianchini F, Bonoli S, Bianchi FB, Lenzi M (2005) HCV liver infection and liver steatosis: evidence for indirect mechanisms in genotype 3? Aliment Pharmacol Ther 22(Suppl 2):79–82PubMedGoogle Scholar
  122. 122.
    Stanzial AM, Benoni G, Cuzzolin L, Gabrielli GB, Pasino M, Perfetti P, Corrocher R (2003) Urinary nitrite/nitrate concentrations and total antioxidant capacity in patients with chronic hepatitis C in therapy with interferon and ribavirin. J Chemother 15:584–590PubMedGoogle Scholar
  123. 123.
    Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, Powell EE (2004) Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 53:413–419PubMedGoogle Scholar

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© SIMI 2008

Authors and Affiliations

  1. 1.Dipartimento Integrato di Medicina, Endocrinologia, Metabolismo e GeriatriaUniversità degli Studi di Modena e Reggio EmiliaModenaItaly
  2. 2.Dipartimento di Medicina Interna, Endocrinologia, Metabolismo e GeriatriaUniversità degli Studi di Modena e Reggio EmiliaModenaItaly

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