Skip to main content
SpringerLink
Log in

Pathogenic interactions between alcohol and hepatitis C

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Alcohol is the most commonly abused substance in the United States, and alcohol abuse leads to alcoholic liver disease, a long recognized major public health concern. The high prevalence of chronic hepatitis C virus (HCV) infection, along with the clinical observation that HCV infection is common in alcoholic patients presenting with liver disease, has directed attention to the interaction between alcohol and HCV infection. Clinical studies have identified alcohol use as an independent risk factor for progression of fibrosis in chronic HCV infection. Experimental evidence suggests additive inhibitory effects between HCV and alcohol on antiviral immune responses. In addition, specific pathways have been identified by which HCV core protein and alcohol interact to activate hepatocytes. Nonspecific inflammatory cell recruitment and proinflammatory cytokine activation have also been implicated in both alcohol-and HCV-induced liver diseases. Further investigation of these and other pathways by which alcohol and HCV interact should unravel the mechanisms that accelerate the progression of liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Liang JT, Rehermann D, Seeff LB, Hoofnagle JH: Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000, 132:296–305.

    PubMed  CAS  Google Scholar 

  2. Schiff ER: The alcoholic patient with HCV infection. Am J Med 1999, 107:95S-99S.

    Article  PubMed  CAS  Google Scholar 

  3. Pessione F, Degos F, Marcellin P, et al.: Effect of alcohol consumption on serum hepatitis c virus RNA and histological lesions in chronic HCV. Hepatology 1998, 27:1717–1722.

    Article  PubMed  CAS  Google Scholar 

  4. Corrano G, Arico S: Independent and combined action of hepatitis c virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology 1998, 27:914–919.

    Article  Google Scholar 

  5. Wiley T, McCarthy M, Breid L, et al.: Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998, 28:805–809.

    Article  PubMed  CAS  Google Scholar 

  6. Vento S, Cainelli F: Does hepatitis C virus cause severe liver disease only in people who drink alcohol? Lancet Infect Dis 2002, 2:303–309. A thought-provoking review of clinical studies and the interaction between alcohol use and HCV infection.

    Article  PubMed  Google Scholar 

  7. Poynard T, Ratziu V, Charlotte F, et al.: Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol 2001, 34:730–739. Recent large-scale analysis of HCV fibrosis progression that identifies alcohol use as an independent risk factor.

    Article  PubMed  CAS  Google Scholar 

  8. Westin J, Lagging LM, Spak F, et al.: Moderate alcohol intake increases fibrosis progression in untreated patients with HCV infection. J Viral Hepat 2002, 9:235–241. This report provides data for disease progression in HCV-infected patients with moderate alcohol use.

    Article  PubMed  Google Scholar 

  9. Cromie SL, Jenkins PJ, Bowden DS, Dudley FJ: Chronic hepatitis C: effect of alcohol on hepatic activity and viral titre. J Hepatol 1996, 25:821–826.

    Article  PubMed  CAS  Google Scholar 

  10. Levy L, Renard C, Wei Y, Buendia M: Genetic alterations and oncogenic pathways in hepatocellular carcinoma. Ann N Y Acad Sci 2002, 963:21–36.

    Article  PubMed  CAS  Google Scholar 

  11. Donato F, Tagger A, Gelatti U, et al.: Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002, 155:323–331.

    Article  PubMed  CAS  Google Scholar 

  12. Hellerbrand C, Hartmann A, Richter G, et al.: Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors. Dig Dis 2001, 19:345–351.

    Article  PubMed  CAS  Google Scholar 

  13. Freeman AJ, Marinos G, French R, Lloyd AR: Immunopathogenesis of hepatitis C infection. Immunol Cell Biol 2001, 79:515–536. A review of the role of the immune system in HCV infection.

    Article  PubMed  CAS  Google Scholar 

  14. Tellinghousen TT, Rice CM: Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol 2002, 5:419–429. A paper summarizing the effects of individual HCV proteins on host cells.

    Article  Google Scholar 

  15. Koziel MJ: Cytokines in viral hepatitis. Semin Liver Dis 1999, 19:157–169.

    PubMed  CAS  Google Scholar 

  16. Kanto T, Hayashi N, Takehara T, et al.: Impaired allostimulatory capacity of peripheral blood dendritic cells recovers from hepatitis C virus-infected individuals. J Immunol 1999, 162:5584–5591.

    PubMed  CAS  Google Scholar 

  17. Auffermann-Gretzinger S, Keeffe EB, Levy S: Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 2001, 97:3171–3176.

    Article  PubMed  CAS  Google Scholar 

  18. Bain C, Fatmi A, Zoulim F, et al.: Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 2001, 120:512–524.

    Article  PubMed  CAS  Google Scholar 

  19. Lechner F, Wong DKH, Dunbar PR, et al.: Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000, 191:1499–1512.

    Article  PubMed  CAS  Google Scholar 

  20. Lechmann M, Woitas RP, Langhans B, et al.: Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C. J Hepatol 1999, 31:971–978.

    Article  PubMed  CAS  Google Scholar 

  21. Rehermann B, Chang K-M, McHutchinson JG, et al.: Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. J Clin Ivest 1996, 98:1432–1440.

    Article  CAS  Google Scholar 

  22. Lancaster T, Sanders E, Christie JML, et al.: Quantitative and functional differences in CD8+ lymphocyte responses in resolved and chronic hepatitis C virus infection. J Viral Hepat 2002, 9:18–28.

    Article  PubMed  CAS  Google Scholar 

  23. Cooper S, Erickson AL, Adams EJ, et al.: Analysis of a successful immune response against hepatitis C infection. Immunity 1999, 10:439–449.

    Article  PubMed  CAS  Google Scholar 

  24. Boisvert J, He X-S, Cheung R, et al.: Quantitative analysis of hepatitis C virus in peripheral blood and liver: replication detected only in liver. J Infect Dis 2001, 184:827–835.

    Article  PubMed  CAS  Google Scholar 

  25. Neuman MG, Benhamou J-P, Malkiewicz I, et al.: Cytokines as predictors for sustained response and as markers for immunomodulation in patients with chronic HCV. Clin Biochem 2001, 34:173–182.

    Article  PubMed  CAS  Google Scholar 

  26. Nelson DR, Lim HL, Marousis CG, et al.: Activation of tumor necrosis factor-alpha system in chronic hepatitis C infection. Dig Dis Sci 1997, 42:2487–2494.

    Article  PubMed  CAS  Google Scholar 

  27. Tseng C-T, Miskovsky E, Houghton M, Klimpel G: Characterizaion of liver T-cell receptor gd+ T cells obtained from individuals chronically infected with HCV. Hepatology 2001, 33:1312–1320.

    Article  PubMed  CAS  Google Scholar 

  28. Szabo G: Consequences of alcohol consumption on host defense. Alcohol Alcohol 1999, 43:830–841. A review of alcohol-induced immune alterations.

    Google Scholar 

  29. Cook RT: Alcohol abuse, alcoholism, and damage to the immune system: a review. Alcohol Clin Exp Res 1998, 22:1927–1942.

    Article  PubMed  CAS  Google Scholar 

  30. Peterson J, Vasquez K, Waltenbaugh C: IL-12 therapy restores cell-mediated immunity in ethanol consuming mice. Alcohol Clin Exp Res 1998, 22:245–251.

    PubMed  CAS  Google Scholar 

  31. McClain C, Barve S, Deaciuc I, et al.: Cytokines in alcoholic liver disease. Semin Liver Dis 1999, 19:205–219.

    Article  PubMed  CAS  Google Scholar 

  32. Bautista AP: Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease. J Gastroenterol Hepatol 2000, 15:349–356.

    Article  PubMed  CAS  Google Scholar 

  33. Pastorino JH and Hoek JB: Ethanol potentiates TNFa cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition. Hepatology 2000, 115:157–166.

    Google Scholar 

  34. Iimuro Y, Gallucci RM, Luster MI, et al.: Antibodies to TNFa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology 1997, 26:1530–1537.

    Article  PubMed  CAS  Google Scholar 

  35. Yin M, Wheeler MD, Kono H, Thurman RG: Essential role for TNF in alcohol-induced liver injury in mice. Gastroenterology 1999, 117:942–952.

    Article  PubMed  CAS  Google Scholar 

  36. Friedman SL: Evaluation of fibrosis and HCV. Am J Med 1999, 107:27S-30S.

    Article  PubMed  CAS  Google Scholar 

  37. Toubi E, Kessel A, Goldstein I, et al.: Enhanced peripheral Tcell apoptosis in chronic hepatitis C virus infection: association with liver disease severity. J Hepatol 2001, 35:774–780.

    Article  PubMed  CAS  Google Scholar 

  38. Natori S, Rust C, Stadheim L, et al.: Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis. J Hepatol 2001, 34:248–253.

    Article  PubMed  CAS  Google Scholar 

  39. Schakel NA, McGuinness PH, Abbott CA, et al.: Insights into the pathobiology of HCV virus-associated cirrhosis. Am J Pathol 2002, 160:641–654. Analysis of gene expression profiles of cirrhosis due to HCV compared with autoimmune hepatitis.

    Google Scholar 

  40. Pianko S, Patella S, Ostapowicz G, et al.: 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, 8:406–413. This study demonstrates increased apoptosis in alcoholic HCVinfected livers and analyzes the role of Fas (CD95) expression.

    Article  PubMed  CAS  Google Scholar 

  41. Galle MB, DeFranco RMS, Kerjaschki D, et al.: Ordered array of dendritic cells and CD8+ lymphocytes in portal infiltrates in chronic hepatitis C. Histopathology 2001, 39:373–381.

    Article  PubMed  CAS  Google Scholar 

  42. Jerrells T: Association of alcohol consumption and exaggerated immunopathologic effects in the liver induced by infectious organism. Front Biosci 2002, 7:1487–1493. A summary of T-cell alterations caused by alcohol use and their impact on liver disease.

    Article  Google Scholar 

  43. Tai DI, Tsai SL, Chen YM, et al.: Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. Hepatology 2000, 31:656–664.

    Article  PubMed  CAS  Google Scholar 

  44. Ghosh S and Karin M: Missing pieces in the NF-kappaB puzzle. Cell 2002, 109:S81-S96.

    Article  PubMed  CAS  Google Scholar 

  45. Szabo G, Catalano D, Bellerose G, Mandrekar P: IFNa and alcohol augment nuclear regulatory factor-kappaB activation in HepG2 cells, and IFNa increases pro-inflammatory cytokine production. Alcohol Clin Exp Res 2001, 25:1188–1197.

    PubMed  CAS  Google Scholar 

  46. Kim W, Hong F, Jagure B, et al.: Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein (HBX) or HCV core protein: involvement of TNFa receptor-1-independent and -dependent mechanisms. FASEB J 2001, 15:2551–2553. This study provides new insights into the pathomechanism of the interaction between HCV and alcohol at the molecular level.

    Article  PubMed  CAS  Google Scholar 

  47. Kato N, Yoshida H, Ono-Nita S, et al.: Activation of intracellular signaling by hepatitis B and C viruses: c-viral core is the most potent signal inducer. Hepatology 2000, 32:405–412.

    Article  PubMed  CAS  Google Scholar 

  48. Anand BS, Velez AM: Influence of chronic alcohol abuse on HCV virus replication. Dig Dis 2000, 18:168–171.

    Article  PubMed  CAS  Google Scholar 

  49. Takahashi K, Takahashi T, Takahashi S, et al.: Hepatitis C virus change by chronic alcohol intake. J Gastroenterol Hepatol 2001, 16:416–423.

    Article  PubMed  CAS  Google Scholar 

  50. Romero-Gomez M, Grande L, Nogales MC, et al.: Intrahepatic HCV replication is increased in patients with regular alcohol consumption. Dig Liver Dis 2001, 33:698–702.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hepatology and Liver Center, Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, 365 Plantation Street, 01605, Worcester, MA, USA

    Gyongyi Szabo MD,PhD

Authors
  1. Gyongyi Szabo MD,PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szabo, G. Pathogenic interactions between alcohol and hepatitis C. Curr Gastroenterol Rep 5, 86–92 (2003). https://doi.org/10.1007/s11894-003-0014-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-003-0014-x

Keywords

Search

Navigation