Abstract
Alcohol abuse is related to a wide variety of medical complications including liver diseases, pancreatitis, cardiovascular diseases, immunological abnormalities, malignant neoplasms, endocrine disturbances, and kidney problems. The liver is the organ most severely affected by alcoholism. Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality in Korea. The mainstay of therapy for alcohol-related medical problems is cessation of drinking. This article summarizes alcohol-related medical complications and treatment with focus on alcoholic liver injury.
Figures and Tables
References
1. Rehm J, Gmel G, Sempos CT, Trevisan M. Alcohol-related morbidity and mortality. Alcohol Res Health. 2003. 27:39–51.
2. Korean health and welfare ministration. 2001 health and nutrition survey. 2002. 81–85.
4. Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000. 95:1505–1523.
6. Stewart S, Jones D, Day CP. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol Med. 2001. 7:408–413.
7. Espina N, Lima V, Lieber CS, Garro AJ. In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase. Carcinogenesis. 1988. 9:761–766.
8. Lieber CS, Baraona E, Hernandez-Munoz R, Kubota S, Sato N, Inatomi N, et al. Impaired oxygen utilization. A new mechanism for the hepatotoxicity of ethanol in sub-human primates. J Clin Invest. 1989. 83:1682–1690.
9. Wondergem R, Davis J. Ethanol increases hepatocyte water volume. Alcohol Clin Exp Res. 1994. 18:1230–1236.
10. Hoerner M, Behrens UJ, Worner T, Lieber CS. Humoral immune response to acetaldehyde adducts in alcoholic patients. Res Commun Chem Pathol Pharmacol. 1986. 54:3–12.
11. Garro AJ, McBeth DL, Lima V, Lieber CS. Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res. 1991. 15:395–398.
12. Lieber CS, DeCarli LM. Hepatic microsomal ethanol-oxidizing system. In vitro characteristics and adaptive properties in vivo. J Biol Chem. 1970. 245:2505–2512.
13. Tsutsumi M, Lasker JM, Shimizu M, Rosman AS, Lieber CS. The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver. Hepatology. 1989. 10:437–446.
14. Sato C, Matsuda Y, Lieber CS. Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. Gastroenterology. 1981. 80:140–148.
15. Whitcomb DC, Block GD. Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA. 1994. 272:1845–1850.
16. Frezza M, di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990. 322:95–99.
17. Palmer RH, Frank WO, Nambi P, Wetherington JD, Fox MJ. Effects of various concomitant medications on gastric alcohol dehydrogenase and the first-pass metabolism of ethanol. Am J Gastroenterol. 1991. 86:1749–1755.
18. Sato N, Lindros KO, Baraona E, Ikejima K, Mezey E, Ramchandani VA, et al. Sex difference in alcohol-related organ injury. Alcohol Clin Exp Res. 2001. 25:40S–45S.
19. Baraona E, Abittan CS, Dohmen K, Moretti M, Pozzato G, Lieber CS, et al. Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res. 2001. 25:502–507.
20. Parrish KM, Dufour MC, Stinson FS, Harford TC. Average daily alcohol consumption during adult life among decedents with and without cirrhosis: the 1986 National Mortality Followback Survey. J Stud Alcohol. 1993. 54:450–456.
21. Potter JF, James OF. Clinical features and prognosis of alcoholic liver disease in respect of advancing age. Gerontology. 1987. 33:380–387.
22. Crabb DW. Ethanol oxidizing enzymes: roles in alcohol metabolism and alcoholic liver disease. Prog Liver Dis. 1995. 13:151–172.
23. Ehrig T, Bosron WF, Li TK. Alcohol and aldehyde dehydrogenase. Alcohol Alcohol. 1990. 25:105–116.
24. Yin SJ, Liao CS, Chen CM, Fan FT, Lee SC. Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: implications for ethanol metabolism and cytotoxicity. Biochem Genet. 1992. 30:203–215.
25. Harada S, Misawa S, Agarwal DP, Goedde HW. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. Am J Hum Genet. 1980. 32:8–15.
26. Crabb DW, Matsumoto M, Chang D, You M. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004. 63:49–63.
27. Shen YC, Fan JH, Edenberg HJ, Li TK, Cui YH, Xia GY, et al. Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism. Alcohol Clin Exp Res. 1997. 21:1272–1277.
28. Lee HC, Lee HS, Jung SH, Yi SY, Jung HK, Kim CY, et al. Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci. 2001. 16:745–750.
29. Tome S, Lucey MR. Review article: current management of alcoholic liver disease. Aliment Pharmacol Ther. 2004. 19:707–714.
30. Teli MR, Day CP, Burt AD, Bennett MK, James OF. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet. 1995. 346:987–990.
31. Becker U, Deis A, Sorensen TI, Gronbaek M, Borch-Johnsen K, Jensen G, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996. 23:1025–1029.
32. Tuyns AJ, Pequignot G. Greater risk of ascitic cirrhosis in females in relation to alcohol consumption. Int J Epidemiol. 1984. 13:53–57.
33. Bosron WF, Ehrig T, Li TK. Genetic factors in alcohol metabolism and alcoholism. Semin Liver Dis. 1993. 13:126–135.
34. Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatology. 1997. 26:143–146.
35. Pares A, Barrera JM, Caballeria J, Ercilla G, Bruguera M, Rodes J, et al. Hepatitis C virus antibodies in chronic alcoholic patients: association with severity of liver injury. Hepatology. 1990. 12:1295–1299.
36. Savolainen VT, Liesto K, Mannikko A, Penttila A, Karhunen PJ. Alcohol consumption and alcoholic liver disease: evidence of a threshold level of effects of ethanol. Alcohol Clin Exp Res. 1993. 17:1112–1117.
37. Skude G, Wadstein J. Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics. Acta Med Scand. 1977. 201:53–58.
38. MacSween RN, Burt AD. Histologic spectrum of alcoholic liver disease. Semin Liver Dis. 1986. 6:221–232.
39. Carithers RL Jr, Herlong HF, Diehl AM, Shaw EW, Combes B, Maddrey WC. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med. 1989. 110:685–690.
40. Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000. 119:1637–1648.
41. Alexander JF, Lischner MW, Galambos JT. Natural history of alcoholic hepatitis. II. The long-term prognosis. Am J Gastroenterol. 1971. 56:515–525.
42. Galambos JT. Natural history of alcoholic hepatitis. 3. Histological changes. Gastroenterology. 1972. 63:1026–1035.
44. Ammann RW, Muellhaupt B. Progression of alcoholic acute to chronic pancreatitis. Gut. 1994. 35:552–556.
45. Durbec JP, Sarles H. Multicenter survey of the etiology of pancreatic diseases. Relationship between the relative risk of developing chronic pancreaitis and alcohol, protein and lipid consumption. Digestion. 1978. 18:337–350.
46. Ahlgren JD. Epidemiology and risk factors in pancreatic cancer. Semin Oncol. 1996. 23:241–250.
47. Velema JP, Walker AM, Gold EB. Alcohol and pancreatic cancer. Insufficient epidemiologic evidence for a causal relationship. Epidemiol Rev. 1986. 8:28–41.
48. Haber PS, Pirola RC, Wilson JS. Clinical update: management of acute pancreatitis. J Gastroenterol Hepatol. 1997. 12:189–197.
49. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg. 1997. 84:1665–1669.
50. Windsor AC, Kanwar S, Li AG, Barnes E, Guthrie JA, Reynolds JV, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998. 42:431–435.
51. Olah A, Pardavi G, Belagyi T, Nagy A, Issekutz A, Mohamed GE. Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate. Nutrition. 2002. 18:259–262.
52. Zakhari S. Alcohol and the cardiovascular system: molecular mechanisms for beneficial and harmful action. Alcohol Health Res World. 1997. 21:21–29.
53. Murray RP, Connett JE, Tyas SL, Bond R, Ekuma O, Barnes GE, et al. Alcohol volume, drinking pattern, and cardiovascular disease morbidity and mortality: is there a U-shaped function? Am J Epidemiol. 2002. 155:242–248.
54. Szabo G. Alcohol's contribution to compromised immunity. Alcohol Health Res World. 1997. 21:30–41.
55. Bagnardi V, Blangiardo M, La Vecchia C, Corrao G. Alcohol consumption and the risk of cancer: a meta-analysis. Alcohol Res Health. 2001. 25:263–270.
56. Emanuele N, Emanuele MA. The endocrine system: alcohol alters critical hormonal balance. Alcohol Health Res World. 1997. 21:53–64.
57. Epstein M. Alcohol's impact on kidney function. Alcohol Health Res World. 1997. 21:84–92.
58. Powell WJ Jr, Klatskin G. Duration of survival in patients with Laennec's cirrhosis. Influence of alcohol withdrawal, and possible effects of recent changes in general management of the disease. Am J Med. 1968. 44:406–420.
59. Merkel C, Marchesini G, Fabbri A, Bianco S, Bianchi G, Gatta A, et al. The course of galactose elimination capacity in patients with alcoholic cirrhosis: possible use as a surrogate marker for death. Hepatology. 1996. 24:820–823.
60. Mendenhall C, Roselle GA, Gartside P, Moritz T. Relationship of protein calorie malnutrition to alcoholic liver disease: a reexamination of data from two Veterans Administration Cooperative Studies. Alcohol Clin Exp Res. 1995. 19:635–641.
61. Cabré E, Rodríguez-Iglesias P, Caballería J, Quer JC, Sánchez-Lombraña JL, Gassull MA, et al. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology. 2000. 32:36–42.
62. Mendenhall CL, Anderson S, Garcia-Pont P, Goldberg S, Kiernan T, Zetterman R, et al. Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone. N Engl J Med. 1984. 311:1464–1470.
63. Maddrey WC, Boitnott JK, Bedine MS, Weber FL Jr, Mezey E, White RI Jr. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978. 75:193–199.
64. Mathurin P, Mendenhall CL, Carithers RL Jr, Ramond MJ, Maddrey WC, Poynard T, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002. 36:480–487.
65. Strieter RM, Remick DG, Ward PA, Spengler RN, Lynch JP 3rd, Kunkel SL, et al. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun. 1988. 155:1230–1236.
66. Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Schneider B, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989. 9:105–113.
67. Pares A, Planas R, Torres M, Caballeria J, Viver JM, Rodes J, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol. 1998. 28:615–621.
68. Mato JM, Alvarez L, Ortiz P, Pajares MA. S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacol Ther. 1997. 73:265–280.
69. Arteel G, Marsano L, Mendez C, Bentley F, McClain CJ. Advances in alcoholic liver disease. Best Pract Res Clin Gastroenterol. 2003. 17:625–647.
70. McClain CJ, Hill DB, Song Z, Chawla R, Watson WH, Barve S, et al. S-Adenosylmethionine, cytokines, and alcoholic liver disease. Alcohol. 2002. 27:185–192.
71. Mato JM, Camara J, Fernandez de Paz J, Caballeria L, Coll S, Rodes J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999. 30:1081–1089.
72. Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest. 1995. 96:2461–2468.
73. de la Maza MP, Petermann M, Bunout D, Hirsch S. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr. 1995. 14:192–196.