Avicenna Journal of Clinical Microbiology and Infection

Published by: Kowsar

New Insights Into the Relationships Among Alcohol Consumption, Hepatocellular Carcinoma and Hepatitis C Virus Infection

Authors Information
1 Department of Microbiology, Research Center for Molecular Medicine, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran
Article Notes and Dates
Avicenna Journal of Clinical Microbiology and Infection: May 2014, 1 (1); e19212.Published Online: April 28, 2014
Article Type: Review Article; Received : January 21, 2014; Revised : February 8, 2014; Accepted : March 13, 2014
DOI: http://dx.doi.org/10.17795/ajcmi-19212

To Cite : Sabouri Ghannad M, Mohammadi A, Kazemian H. New Insights Into the Relationships Among Alcohol Consumption, Hepatocellular Carcinoma and Hepatitis C Virus Infection, Avicenna J Clin Microb Infec. 2014 ;1(1):e19212. doi: 10.17795/ajcmi-19212.

Copyright: Copyright © 0, Avicenna Journal of Clinical Microbiology and Infection. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Seifi SJ, Sabouri Ghannad M. A study of HDV in HBsAg positive patients in Tabriz, Northwestern Iran. Hepat Mon. 2010; 10(2): 110-5[PubMed]
  • 2. Keyvani H, Mohammadi A, Sabouri Ghannad M, Hajabdolbaghi M. The Effect of GBV-C Infection on CD4 Count and Viral Loads in Patients Infected With HIV. Hepat Mon. 2012; 12(1): 39-42[PubMed]
  • 3. Sabouri Ghannad M, Zamani A. The full length hepatitis C virus polyprotein and interactions with the interferon-beta signalling pathways in vitro. Iran Biomed J. 2008; 12(1): 23-34[PubMed]
  • 4. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012; 142(6): 1264-73 e1[DOI][PubMed]
  • 5. Taura N, Fukuda S, Ichikawa T, Miyaaki H, Shibata H, Honda T, et al. Relationship of alpha-fetoprotein levels and development of hepatocellular carcinoma in hepatitis C patients with liver cirrhosis. Exp Ther Med. 2012; 4(6): 972-6[DOI][PubMed]
  • 6. Bartenschlager R, Lohmann V. Novel cell culture systems for the hepatitis C virus. Antiviral Res. 2001; 52(1): 1-17[PubMed]
  • 7. Sabouri Ghannad M, Hojati SA, Mirzaei M, Sahebkar AH. Prevalence of hepatitis B and hepatitis C in patients referred to health centers in the Hamadan province, Iran:an epidemiologic study of infections between 2004 and 2007. Asia Biomed. 2013; 7(5): 619-25[DOI]
  • 8. Seeff LB. Natural history of hepatitis C. Hepatology. 1997; 26(3 Suppl 1): 21S-8S[DOI][PubMed]
  • 9. Alisi A, Ghidinelli M, Zerbini A, Missale G, Balsano C. Hepatitis C virus and alcohol: same mitotic targets but different signaling pathways. J Hepatol. 2011; 54(5): 956-63[DOI][PubMed]
  • 10. Wiley TE, McCarthy M, Breidi L, McCarthy M, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology. 1998; 28(3): 805-9[DOI][PubMed]
  • 11. Singal AK, Anand BS. Mechanisms of synergy between alcohol and hepatitis C virus. J Clin Gastroenterol. 2007; 41(8): 761-72[DOI][PubMed]
  • 12. Kwon SY, Ahn MS, Chang HJ. Clinical significance of hepatitis C virus infection to alcoholics with cirrhosis in Korea. J Gastroenterol Hepatol. 2000; 15(11): 1282-6[PubMed]
  • 13. McCartney EM, Beard MR. Impact of alcohol on hepatitis C virus replication and interferon signaling. World J Gastroenterol. 2010; 16(11): 1337-43[PubMed]
  • 14. Cooper ML. Alcohol and increased behavioral risk for AIDS. Alcohol Health & Research World. 1992; 16(1): 67-72
  • 15. Kaplan AJ, Zone-Smith LK, Hannegan C, Norcross ED. The prevalence of hepatitis C in a regional level I trauma center population. J Trauma. 1992; 33(1): 126-8[PubMed]
  • 16. Peters MG, Terrault NA. Alcohol use and hepatitis C. Hepatology. 2002; 36(5 Suppl 1)-5[DOI][PubMed]
  • 17. Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, et al. Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention. J Hepatol. 2011; 55(1): 45-52[DOI][PubMed]
  • 18. Leggio L, Ferrulli A, Zambon A, Caputo F, Kenna GA, Swift RM, et al. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. Addict Behav. 2012; 37(4): 561-4[DOI][PubMed]
  • 19. Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, et al. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med. 2001; 134(2): 120-4[PubMed]
  • 20. Kubo S, Kinoshita H, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, et al. High malignancy of hepatocellular carcinoma in alcoholic patients with hepatitis C virus. Surgery. 1997; 121(4): 425-9[PubMed]
  • 21. Aizawa Y, Shibamoto Y, Takagi I, Zeniya M, Toda G. Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C. A long term follow-up study after histologic diagnosis. Cancer. 2000; 89(1): 53-9[PubMed]
  • 22. Bellentani S, Pozzato G, Saccoccio G, Crovatto M, Croce LS, Mazzoran L, et al. Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study. Gut. 1999; 44(6): 874-80[PubMed]
  • 23. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut. 1997; 41(6): 845-50[PubMed]
  • 24. Fukushima W, Tanaka T, Ohfuji S, Habu D, Tamori A, Kawada N, et al. Does alcohol increase the risk of hepatocellular carcinoma among patients with hepatitis C virus infection? Hepatol Res. 2006; 34(3): 141-9[DOI][PubMed]
  • 25. Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, Jenab M, et al. Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study. J Natl Cancer Inst. 2011; 103(22): 1686-95[DOI][PubMed]
  • 26. Lieber CS, Seitz HK, Garro AJ, Worner TM. Alcohol-related Diseases and Carcinogenesis. Cancer research. 1979; 39(7 Part 2): 2863-86
  • 27. Duguay L, Coutu D, Hetu C, Joly JG. Inhibition of liver regeneration by chronic alcohol administration. Gut. 1982; 23(1): 8-13[PubMed]
  • 28. Vento S, Cainelli F. Does hepatitis C virus cause severe liver disease only in people who drink alcohol? Lancet Infect Dis. 2002; 2(5): 303-9[PubMed]
  • 29. Gao B. Interaction of alcohol and hepatitis viral proteins: implication in synergistic effect of alcohol drinking and viral hepatitis on liver injury. Alcohol. 2002; 27(1): 69-72[PubMed]
  • 30. Osna NA, Clemens DL, Donohue TM, Jr. Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by ethanol. Biochem Pharmacol. 2003; 66(5): 697-710[PubMed]
  • 31. Kessova IG, Cederbaum AI. The effect of CYP2E1-dependent oxidant stress on activity of proteasomes in HepG2 cells. J Pharmacol Exp Ther. 2005; 315(1): 304-12[DOI][PubMed]
  • 32. Bardag-Gorce F, French BA, Nan L, Song H, Nguyen SK, Yong H, et al. CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation. Exp Mol Pathol. 2006; 81(3): 191-201[DOI][PubMed]
  • 33. Bardag-Gorce F, Li J, French BA, French SW. The effect of ethanol-induced CYP2E1 on proteasome activity: the role of 4-hydroxynonenal. Exp Mol Pathol. 2005; 78(2): 109-15[DOI][PubMed]
  • 34. Osna NA, White RL, Todero S, McVicker BL, Thiele GM, Clemens DL, et al. Ethanol-induced oxidative stress suppresses generation of peptides for antigen presentation by hepatoma cells. Hepatology. 2007; 45(1): 53-61[DOI][PubMed]
  • 35. Szabo G, Dolganiuc A, Mandrekar P, White B. Inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection. Alcohol. 2004; 33(3): 241-9[DOI][PubMed]
  • 36. Dolganiuc A, Kodys K, Kopasz A, Marshall C, Mandrekar P, Szabo G. Additive inhibition of dendritic cell allostimulatory capacity by alcohol and hepatitis C is not restored by DC maturation and involves abnormal IL-10 and IL-2 induction. Alcohol Clin Exp Res. 2003; 27(6): 1023-31[DOI][PubMed]
  • 37. Mandrekar P, Catalano D, Dolganiuc A, Kodys K, Szabo G. Inhibition of myeloid dendritic cell accessory cell function and induction of T cell anergy by alcohol correlates with decreased IL-12 production. J Immunol. 2004; 173(5): 3398-407[PubMed]
  • 38. Oshita M, Hayashi N, Kasahara A, Hagiwara H, Mita E, Naito M, et al. Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C. Hepatology. 1994; 20(5): 1115-20[PubMed]
  • 39. Bruggmann P, Dampz M, Gerlach T, Kravecz L, Falcato L. Treatment outcome in relation to alcohol consumption during hepatitis C therapy: an analysis of the Swiss Hepatitis C Cohort Study. Drug Alcohol Depend. 2010; 110(1-2): 167-71[DOI][PubMed]
  • 40. Balbi M, Donadon V, Ghersetti M, Grazioli S, Valentina GD, Gardenal R, et al. Alcohol and HCV chronic infection are risk cofactors of type 2 diabetes mellitus for hepatocellular carcinoma in Italy. Int J Environ Res Public Health. 2010; 7(4): 1366-78[DOI][PubMed]
  • 41. Nash KL, Woodall T, Brown AS, Davies SE, Alexander GJ. Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis. World J Gastroenterol. 2010; 16(32): 4061-5[PubMed]
  • 42. Choi J. Oxidative stress, endogenous antioxidants, alcohol, and hepatitis C: pathogenic interactions and therapeutic considerations. Free Radic Biol Med. 2012; 52(7): 1135-50[DOI][PubMed]
  • 43. Mas VR, Fassnacht R, Archer KJ, Maluf D. Molecular mechanisms involved in the interaction effects of alcohol and hepatitis C virus in liver cirrhosis. Mol Med. 2010; 16(7-8): 287-97[DOI][PubMed]
  • 44. Siu L, Foont J, Wands JR. Hepatitis C virus and alcohol. Semin Liver Dis. 2009; 29(2): 188-99[DOI][PubMed]
  • 45. Sherman KE, Rouster SD, Mendenhall C, Thee D. Hepatitis cRNA quasispecies complexity in patients with alcoholic liver disease. Hepatology. 1999; 30(1): 265-70[DOI][PubMed]
  • 46. Takahashi K, Takahashi T, Takahashi S, Watanabe K, Boku S, Matsui S, et al. Difference in quasispecies of the hypervariable region 1 of hepatitis C virus between alcoholic and non-alcoholic patients. J Gastroenterol Hepatol. 2001; 16(4): 416-23[PubMed]
  • 47. Dolganiuc A, Kodys K, Kopasz A, Marshall C, Do T, Romics L, Jr, et al. Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol. 2003; 170(11): 5615-24[PubMed]
  • 48. Pachiadakis I, Pollara G, Chain BM, Naoumov NV. Is hepatitis C virus infection of dendritic cells a mechanism facilitating viral persistence? Lancet Infect Dis. 2005; 5(5): 296-304[DOI][PubMed]
  • 49. Rigamonti C, Mottaran E, Reale E, Rolla R, Cipriani V, Capelli F, et al. Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C. Hepatology. 2003; 38(1): 42-9[DOI][PubMed]
  • 50. Farinati F, Cardin R, De Maria N, Della Libera G, Marafin C, Lecis E, et al. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol. 1995; 22(4): 449-56[PubMed]
  • 51. Tsukamoto H, Lin M, Ohata M, Giulivi C, French SW, Brittenham G. Iron primes hepatic macrophages for NF-kappaB activation in alcoholic liver injury. Am J Physiol. 1999; 277(6 Pt 1)-50[PubMed]
  • 52. Wheeler MD. Endotoxin and Kupffer cell activation in alcoholic liver disease. Alcohol Res Health. 2003; 27(4): 300-6[PubMed]
  • 53. Koike K, Tsutsumi T, Miyoshi H, Shinzawa S, Shintani Y, Fujie H, et al. Molecular basis for the synergy between alcohol and hepatitis C virus in hepatocarcinogenesis. J Gastroenterol Hepatol. 2008; 23 Suppl 1-91[DOI][PubMed]
  • 54. Koike K, Moriya K, Ishibashi K, Matsuura Y, Suzuki T, Saito I, et al. Expression of hepatitis C virus envelope proteins in transgenic mice. J Gen Virol. 1995; 76 ( Pt 12): 3031-8[PubMed]
  • 55. Moriya K, Todoroki T, Tsutsumi T, Fujie H, Shintani Y, Miyoshi H, et al. Increase in the concentration of carbon 18 monounsaturated fatty acids in the liver with hepatitis C: analysis in transgenic mice and humans. Biochem Biophys Res Commun. 2001; 281(5): 1207-12[DOI][PubMed]
  • 56. Okuda M, Li K, Beard MR, Showalter LA, Scholle F, Lemon SM, et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology. 2002; 122(2): 366-75[PubMed]
  • 57. Tsutsumi T, Suzuki T, Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, et al. Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic mice expressing hepatitis C virus core protein. Virology. 2002; 304(2): 415-24[PubMed]
  • 58. Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, et al. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002; 35(4): 937-46[DOI][PubMed]
  • 59. Tsutsumi T, Suzuki T, Moriya K, Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice. Hepatology. 2003; 38(4): 820-8[DOI][PubMed]
  • 60. Szabo G, Wands JR, Eken A, Osna NA, Weinman SA, Machida K, et al. Alcohol and hepatitis C virus--interactions in immune dysfunctions and liver damage. Alcohol Clin Exp Res. 2010; 34(10): 1675-86[DOI][PubMed]
  • 61. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005; 5(10): 749-59[DOI][PubMed]
  • 62. Bain C, Fatmi A, Zoulim F, Zarski JP, Trepo C, Inchauspe G. Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology. 2001; 120(2): 512-24[PubMed]
  • 63. Siavoshian S, Abraham JD, Thumann C, Kieny MP, Schuster C. Hepatitis C virus core, NS3, NS5A, NS5B proteins induce apoptosis in mature dendritic cells. J Med Virol. 2005; 75(3): 402-11[DOI][PubMed]
  • 64. Crotta S, Stilla A, Wack A, D'Andrea A, Nuti S, D'Oro U, et al. Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein. J Exp Med. 2002; 195(1): 35-41[PubMed]
  • 65. Averill L, Lee WM, Karandikar NJ. Differential dysfunction in dendritic cell subsets during chronic HCV infection. Clin Immunol. 2007; 123(1): 40-9[DOI][PubMed]
  • 66. Seifert U, Liermann H, Racanelli V, Halenius A, Wiese M, Wedemeyer H, et al. Hepatitis C virus mutation affects proteasomal epitope processing. J Clin Invest. 2004; 114(2): 250-9[DOI][PubMed]
  • 67. Khu YL, Tan YJ, Lim SG, Hong W, Goh PY. Hepatitis C virus non-structural protein NS3 interacts with LMP7, a component of the immunoproteasome, and affects its proteasome activity. Biochem J. 2004; 384: 401-9[DOI][PubMed]
  • 68. Pianko S, Patella S, Ostapowicz G, Desmond P, Sievert W. Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection. J Viral Hepat. 2001; 8(6): 406-13[PubMed]
  • 69. Schiff ER. The alcoholic patient with Hepatitis C Virus infection. Am J Med. 1999; 107(6): 95-9
  • 70. Zhang T, Li Y, Lai JP, Douglas SD, Metzger DS, O'Brien CP, et al. Alcohol potentiates hepatitis C virus replicon expression. Hepatology. 2003; 38(1): 57-65[DOI][PubMed]
  • 71. Cook RT. Alcohol abuse, alcoholism, and damage to the immune system--a review. Alcohol Clin Exp Res. 1998; 22(9): 1927-42[PubMed]
  • 72. Pessione F, Degos F, Marcellin P, Duchatelle V, Njapoum C, Martinot-Peignoux M, et al. Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C. Hepatology. 1998; 27(6): 1717-22[DOI][PubMed]
  • 73. Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology. 1998; 27(4): 914-9[DOI][PubMed]
  • 74. Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002; 155(4): 323-31[PubMed]
  • 75. Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002; 36(5): 1206-13[DOI][PubMed]
  • 76. Kovach SJ, Sitzmann JV, McKillop IH. Inhibition of alcohol dehydrogenase blocks enhanced Gi-protein expression following ethanol treatment in experimental hepatocellular carcinoma in vitro. Eur J Gastroenterol Hepatol. 2001; 13(10): 1209-16[PubMed]
  • 77. Noda K, Yoshihara H, Suzuki K, Yamada Y, Kasahara A, Hayashi N, et al. Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma--its relationship to alcohol drinking and the age of transfusion. Alcohol Clin Exp Res. 1996; 20(1 Suppl): 95A-100A[PubMed]
  • 78. Ostapowicz G, Watson KJ, Locarnini SA, Desmond PV. Role of alcohol in the progression of liver disease caused by hepatitis C virus infection. Hepatology. 1998; 27(6): 1730-5[DOI][PubMed]
  • 79. Schiff ER. Hepatitis C and alcohol. Hepatology. 1997; 26(3 Suppl 1): 39S-42S[DOI][PubMed]
  • 80. Westin J, Lagging LM, Spak F, Aires N, Svensson E, Lindh M, et al. Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection. J Viral Hepat. 2002; 9(3): 235-41[PubMed]
  • 81. Kotoh K, Fukushima M, Horikawa Y, Yamashita S, Kohjima M, Nakamuta M, et al. Serum albumin is present at higher levels in alcoholic liver cirrhosis as compared to HCV-related cirrhosis. Exp Ther Med. 2012; 3(1): 72-5[DOI][PubMed]
  • 82. Loguercio C, Di Pierro M, Di Marino MP, Federico A, Disalvo D, Crafa E, et al. Drinking habits of subjects with hepatitis C virus-related chronic liver disease: prevalence and effect on clinical, virological and pathological aspects. Alcohol Alcohol. 2000; 35(3): 296-301[PubMed]
  • 83. Anand BS, Currie S, Dieperink E, Bini EJ, Shen H, Ho SB, et al. Alcohol use and treatment of hepatitis C virus: results of a national multicenter study. Gastroenterology. 2006; 130(6): 1607-16[DOI][PubMed]
  • 84. Chang A, Skole K, Gautam M, Schmutz J, Black M, Thomas R, et al. The impact of past alcohol use on treatment response rates in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2005; 22(8): 701-6[DOI][PubMed]
  • 85. Mochida S, Ohnishi K, Matsuo S, Kakihara K, Fujiwara K. Effect of alcohol intake on the efficacy of interferon therapy in patients with chronic hepatitis C as evaluated by multivariate logistic regression analysis. Alcohol Clin Exp Res. 1996; 20(9 Suppl): 371A-7A[PubMed]
  • 86. Tabone M, Sidoli L, Laudi C, Pellegrino S, Rocca G, Della Monica P, et al. Alcohol abstinence does not offset the strong negative effect of lifetime alcohol consumption on the outcome of interferon therapy. J Viral Hepat. 2002; 9(4): 288-94[PubMed]
  • 87. Plumlee CR, Lazaro CA, Fausto N, Polyak SJ. Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells. Virol J. 2005; 2: 89[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Cited By:

Search Relations:


  • Masoud Sabouri Ghannad: [PubMed] [Scholar]
  • Avid Mohammadi: [PubMed] [Scholar]
  • Hamid Kazemian: [PubMed] [Scholar]
  • Related Article in PubMed
  • Related Article in Google Scholar

Create Citiaion Alert via Google Reader