We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20–4.67]; GGT, 1.91 [1.17–3.13]). Only GGT level (odds ratio 6.04 [3.68–9.94], SI 2.33 [1.24–4.41]) was significantly elevated when the effect of moderate drinking (<24 g/day) and metabolic syndrome was combined. The combined effect of any level of alcohol consumption and cigarette smoking was also supra-additive on the elevation of GGT level with SIs of 5.57 for drinking <24 g/day and smoking ≤20 pack years, 5.12 for <24 g/day and >20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12–6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.
References
[1]
Clark JM, Brancati FL, Diehl AM (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98: 960–967.
[2]
Oh SY, Cho YK, Kang MS, Yoo TW, Park JH, et al. (2006) The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease. Metabolism 55: 1604–1609.
[3]
Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, et al. (2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42: 44–52.
[4]
Bellentani S, Scaglioni F, Marino M, Bedogni G (2010) Epidemiology of non-alcoholic fatty liver disease. Dig Dis 28: 155–161.
[5]
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, et al. (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40: 1387–1395.
[6]
Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F (2013) The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol 58: 593–608.
[7]
Farrell GC, Wong VW, Chitturi S (2013) NAFLD in Asia-as common and important as in the West. Nat Rev Gastroenterol Hepatol.
[8]
Schindhelm RK, Dekker JM, Nijpels G, Bouter LM, Stehouwer CD, et al. (2007) Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis 191: 391–396.
[9]
Meisinger C, Doring A, Schneider A, Lowel H (2006) Serum gamma-glutamyltransferase is a predictor of incident coronary events in apparently healthy men from the general population. Atherosclerosis 189: 297–302.
[10]
Sattar N, McConnachie A, Ford I, Gaw A, Cleland SJ, et al. (2007) Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor. Diabetes 56: 984–991.
[11]
Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, et al. (2007) Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 13: 1579–1584.
[12]
Bellentani S, Marino M (2009) Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 8 Suppl 1S4–8.
[13]
Clark JM, Brancati FL, Diehl AM (2002) Nonalcoholic fatty liver disease. Gastroenterology 122: 1649–1657.
[14]
Lanthier N, Horsmans Y, Leclercq IA (2009) The metabolic syndrome: how it may influence hepatic stellate cell activation and hepatic fibrosis. Curr Opin Clin Nutr Metab Care 12: 404–411.
[15]
Liou I, Kowdley KV (2006) Natural history of nonalcoholic steatohepatitis. J Clin Gastroenterol 40 Suppl 1S11–16.
[16]
Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, et al. (2007) Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 49: 403–414.
[17]
Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, et al. (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288: 2709–2716.
[18]
Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB (2005) Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112: 3066–3072.
[19]
Li M, Campbell S, McDermott R (2009) gamma-Glutamyltransferase, obesity, physical activity, and the metabolic syndrome in indigenous Australian adults. Obesity (Silver Spring) 17: 809–813.
[20]
Hsieh MH, Ho CK, Hou NJ, Hsieh MY, Lin WY, et al. (2009) Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C. Int J Obes (Lond). 33: 1309–1317.
[21]
Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, et al. (1997) Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut 41: 845–850.
[22]
Puukka K, Hietala J, Koivisto H, Anttila P, Bloigu R, et al.. (2006) Additive effects of moderate drinking and obesity on serum gamma-glutamyl transferase activity. Am J Clin Nutr 83: 1351–1354; quiz 1448–1359.
[23]
Gunji T, Matsuhashi N, Sato H, Fujibayashi K, Okumura M, et al. (2009) Light and moderate alcohol consumption significantly reduces the prevalence of fatty liver in the Japanese male population. Am J Gastroenterol 104: 2189–2195.
[24]
Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, et al. (2012) Protective effect of alcohol consumption for fatty liver but not metabolic syndrome. World J Gastroenterol 18: 156–167.
[25]
Hiramine Y, Imamura Y, Uto H, Koriyama C, Horiuchi M, et al. (2011) Alcohol drinking patterns and the risk of fatty liver in Japanese men. J Gastroenterol 46: 519–528.
[26]
Adams LA, Knuiman MW, Divitini ML, Olynyk JK (2008) Body mass index is a stronger predictor of alanine aminotransaminase levels than alcohol consumption. J Gastroenterol Hepatol 23: 1089–1093.
[27]
Bataller R (2006) Time to ban smoking in patients with chronic liver diseases. Hepatology 44: 1394–1396.
[28]
Azzalini L, Ferrer E, Ramalho LN, Moreno M, Dominguez M, et al. (2010) Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats. Hepatology 51: 1567–1576.
[29]
El-Zayadi AR (2006) Heavy smoking and liver. World J Gastroenterol 12: 6098–6101.
[30]
Pessione F, Ramond MJ, Njapoum C, Duchatelle V, Degott C, et al. (2001) Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology. 34: 121–125.
[31]
Koh WP, Robien K, Wang R, Govindarajan S, Yuan JM, et al. (2011) Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study. Br J Cancer 105: 1430–1435.
[32]
National Institute on Alcohol Abuse and Alcoholism (1992) Moderate drinking. Alcohol Alert No.16.
[33]
WHO expert consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363: 157–163.
[34]
Shin A, Lim SY, Sung J, Shin HR, Kim J (2009) Dietary intake, eating habits, and metabolic syndrome in Korean men. J Am Diet Assoc 109: 633–640.
[35]
National Cholesterol Education Program Expert Panel (2002) Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Bethesda: National Institutes of Health.
Sakugawa H, Nakayoshi T, Kobashigawa K, Nakasone H, Kawakami Y, et al. (2004) Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women. World J Gastroenterol 10: 1052–1055.
[38]
Hamabe A, Uto H, Imamura Y, Kusano K, Mawatari S, et al. (2011) Impact of cigarette smoking on onset of nonalcoholic fatty liver disease over a 10-year period. J Gastroenterol 46: 769–778.
[39]
Breitling LP, Raum E, Muller H, Rothenbacher D, Brenner H (2009) Synergism between smoking and alcohol consumption with respect to serum gamma-glutamyltransferase. Hepatology 49: 802–808.
[40]
Haren MT, Li M, Petkov J, McDermott RA (2010) Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians. BMC Public Health 10: 454.
[41]
Bellentani S, Tiribelli C, Saccoccio G, Sodde M, Fratti N, et al. (1994) Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. Hepatology 20: 1442–1449.
[42]
Lee DH, Ha MH, Christiani DC (2001) Body weight, alcohol consumption and liver enzyme activity–a 4-year follow-up study. Int J Epidemiol 30: 766–770.
[43]
Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114: 147–152.
[44]
McClain CJ, Mokshagundam SP, Barve SS, Song Z, Hill DB, et al. (2004) Mechanisms of non-alcoholic steatohepatitis. Alcohol 34: 67–79.
[45]
Nobili V, Alisi A, Raponi M (2009) Pediatric non-alcoholic fatty liver disease: preventive and therapeutic value of lifestyle intervention. World J Gastroenterol 15: 6017–6022.
[46]
Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, et al.. (2010) SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 138: 1357–1364, 1364 e1351–1352.
[47]
Zheng MH, Shi KQ, Fan YC, Liu WY, Lin XF, et al. (2012) Upper limits of normal for serum alanine aminotransferase levels in Chinese Han population. PLoS One 7: e43736.
[48]
Kim HC, Nam CM, Jee SH, Han KH, Oh DK, et al. (2004) Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ 328: 983.
[49]
Yoon YS, Oh SW, Park HS (2006) Socioeconomic status in relation to obesity and abdominal obesity in Korean adults: a focus on sex differences. Obesity (Silver Spring) 14: 909–919.
[50]
Lim H, Nguyen T, Choue R, Wang Y (2012) Sociodemographic disparities in the composition of metabolic syndrome components among adults in South Korea. Diabetes Care 35: 2028–2035.
[51]
Park SJ, Kang HT, Nam CM, Park BJ, Linton JA, et al. (2012) Sex differences in the relationship between socioeconomic status and metabolic syndrome: the Korean National Health and Nutrition Examination Survey. Diabetes Res Clin Pract 96: 400–406.
