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Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis

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Abstract

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables, a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.

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References

  1. Sørensen TIA. Alcohol and liver injury: Dose related or permissive effect? Liver 1989; 9: 189–197.

    PubMed  Google Scholar 

  2. Saunders JB, Latt N. Epidemiology of alcoholic liver disease. Bailliere's Clinical Gastroenterology 1993; 7: 555–579.

    PubMed  Google Scholar 

  3. Lieber CS. Aetiology and pathogenesis of alcoholic liver disease. Bailliere's Clinical Gastroenterology 1993; 7: 581–608.

    PubMed  Google Scholar 

  4. Derr RF, Porta EA, Larkin EC, Rao GA. Is ethanol per se hepatotoxic? J Hepatol 1990; 10: 381–386.

    PubMed  Google Scholar 

  5. Sørensen TIA, Bentsen KD, Eghöje KN. Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis. Lancet 1984; 2: 241–244.

    Article  PubMed  Google Scholar 

  6. Patek AJ, Toth IG, Saunders MG, Castro GAH, Emgel JI. Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients. Arch Intern Med 1975; 135: 1053–1057.

    Article  PubMed  Google Scholar 

  7. Chevillotte G, Durhec JP, Gerolami A. Interaction between hepatitis B virus and alcohol consumption in liver cirrhosis. Gastroenterology 1983; 85: 141–145.

    PubMed  Google Scholar 

  8. Villa E, Baldini G, Di Stabile S. Alcohol and hepatitis B virus infection. Acta Med Scand 1985; 703: 97–101.

    Google Scholar 

  9. Nomura H, Kashiwagy S, Hayashi J. An epidemiological study of effects of alcohol in the liver in hepatitis B surface antigens carriers. Am J Epidemiol 1988; 128: 277–284.

    PubMed  Google Scholar 

  10. Chung HT, Lai CL, Wu PC. Synergism of chronic alcoholism in hepatitis B infection in liver disease. J Gastroenterol Hepatol 1989; 4: 11–16.

    PubMed  Google Scholar 

  11. Brillanti S, Barbara L, Miglioli M, Bonino F. Hepatitis C virus: A possible cause of chronic hepatitis in alcoholies. Lancet 1989; 2: 1390–1391.

    Article  Google Scholar 

  12. Tabone M, Galatola G, Corrao G, Aricò S. Anti-HCV antibodies in patients with chronic liver disease and different amounts of alcohol intake: A multivariate analysis. Eur J Gastroenterol Hepatol 1993; 5: 749–754.

    Google Scholar 

  13. Corrao G, Carle F, Lepore AR, Zepponi E, Galatola G, di Orio F. Interaction between alcohol consumption and positivity for antibodies to hepatitis C virus on the risk of liver cirrhosis: A case-control study. Eur J Epidemiol 1992; 8: 634–639.

    PubMed  Google Scholar 

  14. Corrao G, Ferrari PA, Galatola G. Exploring the role of diet in modifying the effect of known disease determinants: Application to risk factor of liver cirrhosis. Am J Epidemiol 1995; 142: 1136–1146.

    PubMed  Google Scholar 

  15. Corrao G, Busellu GP, Valenti M, Torchio PF, Galatola G, di Orio F. Reproducibility of measuring lifetime alcohol consumption by a simple interview administered questionnaire. Alcologia 1994; 6: 127–135.

    Google Scholar 

  16. Aricò S, Galatola G, Tabone M, et al. The measure of lifetime alcohol consumption in cirrhotic patients: Reproducibility and clinical relevance. Liver 1995; 15: 202–208.

    PubMed  Google Scholar 

  17. Van Der Poel, Reesing HW, Schaasberg W. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990; 335: 558–560.

    Article  PubMed  Google Scholar 

  18. Breslow NE, Day NE. Statistical methods in cancer research. Vol. I The analysis of case-control studies. IARC Scientific Publications No 32. Lyon: International Agency for Research on Cancer, 1980.

    Google Scholar 

  19. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies. J Natl Cancer Inst 1959; 22: 719–748.

    PubMed  Google Scholar 

  20. Mantel N. Chi-square tests with one degree of freedom: Extension of the Mantel-Haenszel procedure. J Am Stat Assoc 1963; 59: 690–700.

    Google Scholar 

  21. Rothman KJ. The estimation of synergy or antagonism. Am J Epidemiol 1976; 103: 506–511.

    PubMed  Google Scholar 

  22. Breslow NE, Storer BE. General relative risk functions for case-control studies. Am J Epidemiol 1985; 122: 149–162.

    PubMed  Google Scholar 

  23. McCullagh RJ, Nelder JA. Generalized linear models. Cambridge: Chapman and Hall University Press, 1988.

    Google Scholar 

  24. Baker RJ, Nelder JA. The GLIM System. Release 3.77. Oxford: Numerical Algorithms Group, 1985.

    Google Scholar 

  25. EGRET Reference Manual. Statistics and Epidemiology Research Corporation and Cytel Software Corporation. 1990.

  26. Caldwell SH, Li X, Rourk RM. Hepatitis C infection by polymerase chain reaction in alcoholics: False positive ELISA results and the influence of infection on a clinical prognosis score. Am J Gastroenterol 1993; 88: 1016–1021.

    PubMed  Google Scholar 

  27. Nakano M, Maruyama K, Okuyama K, et al. The characteristics of alcoholies with HCV infection: Histopathologic comparison with alcoholics without HCV infection and chronic type C hepatitis. Alcohol Alcohol Suppl 1993; 1: 35–40.

    Google Scholar 

  28. Santos A, Carvalho A, Bento D. Hepatitis C epidemiology in the central area of Portugal. Prevalence of anti-HCV in the population of the district of Coimbra. Acta Med Port 1993; 6: 567–572.

    PubMed  Google Scholar 

  29. Ishii K, Furudera S, Tanaka S. Chronic hepatitis C in alcoholic patients: Studies with various HCV assay procedure. Alcohol Alcohol Suppl 1993; 1: 71–76.

    Google Scholar 

  30. Befrits R, Hedman M, Blomquist L, et al. Chronic hepatitis C in alcoholic patients: Prevalence, genotypes, and correlation to liver disease. Scand J Gastroenterol 1995; 30: 1113–1118.

    PubMed  Google Scholar 

  31. Coclho-Little ME, Jeffers LJ, Bernstein DE, et al. Hepatitis C virus in alcoholic patients with and without clinically apparent liver disease. Alcohol Clin Exp Res 1995; 19: 1173–1176.

    PubMed  Google Scholar 

  32. Bird GL, Tibbs CJ, Orton D, et al. Does hepatitis C contribute to liver injury in alcohol abusers in the west of Scotland? Eur J Gastroenterol Hepatol 1995; 7: 161–163.

    PubMed  Google Scholar 

  33. Freni MA, Ajello A, Resta ML. HCV infection, hepatic HLA display and composition of the mononuclear cell inflammatory infiltrate in chronic alcoholic liver disease. Eur J Clin Invest 1991; 21: 586–591.

    PubMed  Google Scholar 

  34. Brillanti S, Masci C, Siringo S, Di Febo G, Miglioli M, Barbara L. Serological and histological aspects of hepatitis C virus infection in alcoholic patients. J Hepatol 1991; 13: 347–350.

    PubMed  Google Scholar 

  35. Shiomi S, Kuroki T, Minanitami S. Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C. J Gastroenterol Hepatol 1992; 7: 274–276.

    PubMed  Google Scholar 

  36. Amarapurkar DN, Kumar A, Parikh SS, et al. Hepatitis C virus infection in chronic liver disease in Bombay. Indian J Gastroenterol 1992; 11: 162–163.

    PubMed  Google Scholar 

  37. Tsai JF, Chang WY, Jeng JE. Hepatitis C virus infection as a risk factor for non-alcoholic liver cirrhosis in Taiwan. J Med Virol 1993; 41: 296–300.

    PubMed  Google Scholar 

  38. Takase S, Takada N, Sawada M, Tsutsumi M, Takada A. Relationship between alcoholic liver disease and HCV infection. Alcohol Alcohol Suppl 1993; 1: 77–84.

    Google Scholar 

  39. Chang TT, Lin CY, Chow NH. Hepatitis B and hepatitis C virus infection among chronic alcoholic patients with liver disease in Taiwan. J Formos Med Assoc 1994; 93: 128–133.

    PubMed  Google Scholar 

  40. Deny P, Halimi C, Trinchet JC, et al. Role du virus de l'hepatite C dans la genese des lesions hepatiques observees chez des malades alcooliques atteints de cirrhose. Gastroenterol Clin Biol 1994; 18: 110–114.

    PubMed  Google Scholar 

  41. Serfaty L, Nousbaum JB, Elghouzzi MH, Giral P, Legendre C, Poupon R. Prevalence, severity, and risk factors of liver disease in blood donors positive in a second-generation anti-hepatitis C virus screening test. Hepatology 1995; 21: 725–729.

    Article  PubMed  Google Scholar 

  42. Nalpas B, Thiers V, Pol S, et al. Hepatitis C viremia and anti-HCV antibodies in alcoholies. J Hepatol 1992; 14: 381–384.

    PubMed  Google Scholar 

  43. Thomas DC. General relative risk models for survival time and matched case-control analysis. Biometries 1981; 37: 673–686.

    Google Scholar 

  44. Guerrero VM, Johnson RA. Use of the Box-Cox transformation with binary response models. Biometrika 1982; 69: 309–314.

    Google Scholar 

  45. Valseechi MG. Modelling the relative risk of esophageal cancer in case-control study. J Clin Epidemiol 1992; 45: 347–355.

    Article  PubMed  Google Scholar 

  46. Orrego H, Blendis LM, Blake JE. Unreliability of assessment of alcohol intake based on personal interviews in a liver clinic. Lancet 1979; 2: 1354–1356.

    Article  PubMed  Google Scholar 

  47. Aricò S, Galatola G, Tabone M, Corrao G. Amount and duration of alcohol intake in patients with chronic liver disease: An Italian multicentric study. It J Gastroenterol 1994; 26: 59–65.

    Google Scholar 

  48. Pol S, Thiers V, Nalpas B, Degos F, Gazengel C, Carnot F, Tiollais P, Wands JR, Berthelot P, Brechot C. Monoclonal anti-HBs antibodies radioimmunoassay and serum HBV-DNA hybridization as diagnostic tools of HBV infection: Relative prevalence among HBsAgnegative alcoholics, patients with chronic hepatitis or hepatocellular carcinomas and blood donors. Eur J Clin Invest 1987; 17: 515–521.

    PubMed  Google Scholar 

  49. D'Amico G, Morabito A, Pagliaro L, Marubini E. Survival and prognostic indicators in compensed and decompensed cirrhosis. Digest Dis Sci 1986; 31: 468–475.

    PubMed  Google Scholar 

  50. Corrao G, Aricò S, Russo R, et al. Alcohol consumption and non-cirrhotic chronic hepatitis: A case-control study. Int J Epidemiol 1991; 20: 1037–1042.

    PubMed  Google Scholar 

  51. Corrao G, Aricò S, Carle F, et al. A case-control study on alcohol consumption and the risk of chronic liver disease. Revue Epidemiol Sante 1991; 39: 333–343.

    Google Scholar 

  52. Corrao G, Aricò S, Lepore AR, et al. Amount and duration of alcohol intake as risk factor of symptomatic liver cirrhosis: A case-control study. J Clin Epidemiol 1993; 46: 601–607.

    Article  PubMed  Google Scholar 

  53. Mendenhall CL, Moritz T, Chedid A, et al. Relevance of anti-HCV reactivity in patients with alcoholic hepatitis. VA cooperative study Group 275. Gastroenterol Jpn 1993; 28(suppl.): 95–100.

    Google Scholar 

  54. Sherlock DS. Chronic hepatitis C. Dis Mon 1994; 40: 117–196.

    PubMed  Google Scholar 

  55. West DW, Schuman KL, Lyon JL. Differences in risk estimation from a population-based case-control study. Int J Epidemiol 1984; 13: 235–239.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Statistics, University of Milan, ITALY

    Giovanni Corrao, Pierfederico Torchio, Antonella Zambon & Pieralda Ferrari

  2. Division of Gastroenterology, Hospital Mauriziano Umberto I, Turin

    Sarino Aricò

  3. Department of Internal Medicine and Public Health, University of L'Aquila, Italy

    Ferdinando di Orio

Authors
  1. Giovanni Corrao
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  2. Pierfederico Torchio
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  3. Antonella Zambon
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  4. Pieralda Ferrari
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  5. Sarino Aricò
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  6. Ferdinando di Orio
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Corrao, G., Torchio, P., Zambon, A. et al. Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis. Eur J Epidemiol 14, 447–456 (1998). https://doi.org/10.1023/A:1007411423766

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