Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease
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Background/Aims: Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD. Methods: A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day. Results: The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse,dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001). Conclusions: Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD. (Clin Mol Hepatol 2012;18:383-390)
Abstract
Background/Aims: Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD. Methods: A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day. Results: The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse,dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001). Conclusions: Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD. (Clin Mol Hepatol 2012;18:383-390)
참고문헌 (36)
- Browning JD, "Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity", Hepatology, 40, pp.1387~1395 (2004)
- Neuschwander-Tetri BA, "Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference", Hepatology, 37, pp.1202~1219 (2003)
- Salamone F, "Nonalcoholic fatty liver disease: the hepatic trigger of the metabolic syndrome", J Hepatol, 53, pp.1146~1147 (2010)
- Choi SY, "The Relation Between Non-Alcoholic Fatty Liver Disease and the Risk of Coronary Heart Disease in Koreans", AMERICAN JOURNAL OF GASTROENTEROLOGY, 104, pp.1953~1960 (2009), NATURE PUBLISHING GROUP
- Speliotes EK, "Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study", Hepatology, 51, pp.1979~1987 (2010)
- Chen SH, "Relationship between nonalcoholic fatty liver disease and metabolic syndrome", J Dig Dis, 12, pp.125~130 (2011)
- Oliveira CP, "Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet", J Cell Mol Med, 6, pp.399~406 (2002)
- Sumida Y, "Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease", J Hepatol, 38, pp.32~38 (2003)
- Seki S, "Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases", Hepatol Res, 33, pp.132~134 (2005)
- Morita M, "Fatty liver induced by free radicals and lipid peroxidation", Free Radic Res, 46, pp.758~765 (2012)
- Terao K, "Damage to biological tissues induced by radical initiator 2,2’-azobis(2-amidinopropane) dihydrochloride and its inhibition by chain-breaking antioxidants", J Free Radic Biol Med, 2, pp.193~201 (1986)
- Shimasaki H, "Free radical-induced liver injury. II. Effects of intraperitoneally administered 2,2’-azobis(2-amidinopropane) dihydrochloride on the fatty acid profiles of hepatic triacylglycerol and phospholipids", Free Radic Res Commun, 14, pp.247~252 (1991)
- Sanyal AJ, "A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis", Clin Gastroenterol Hepatol, 2, pp.1107~1115 (2004)
- Stocker R, "Bilirubin is an antioxidant of possible physiological importance", Science, 235, pp.1043~1046 (1987)
- Baranano DE, "Biliverdin reductase: a major physiologic cytoprotectant", Proc Natl Acad Sci U S A, 99, pp.16093~16098 (2002)
- Stocker R, "Antioxidant activities of bile pigments", Antioxid Redox Signal, 6, pp.841~849 (2004)
- Lin LY, "Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents", Atherosclerosis, 203, pp.563~568 (2009)
- Cheriyath P, "High Total Bilirubin as a Protective Factor for Diabetes Mellitus: An Analysis of NHANES Data From 1999 - 2006", J Clin Med Res, 2, pp.201~206 (2010)
- Lin JP, "Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study", Circulation, 114, pp.1476~1481 (2006)
- Perlstein TS, "Serum total bilirubin level, prevalent stroke, and stroke outcomes: NHANES 1999-2004", Am J Med, 121, pp.781~788.e1 (2008)
- Chang Y, "A Cohort Study of Serum Bilirubin Levels and Incident Non-Alcoholic Fatty Liver Disease in Middle Aged Korean Workers", PLOS ONE, 7(5), pp.e37241~ (2012), Public Library of Science
- Hjelkrem M, "Unconjugated hyperbilirubinemia is inversely associated with non-alcoholic steatohepatitis (NASH)", Aliment Pharmacol Ther, 35, pp.1416~1423 (2012)
- Kumar R, "Unconjugated hyperbilirubinemia in patients with non-alcoholic fatty liver disease: a favorable endogenous response", Clin Biochem, 45, pp.272~274 (2012)
- Grundy SM, "Diagnosis and management of the metabolic syndrome: an American Heart Association", National Heart, Lung, and Blood Institute Scientific Statement, 2005, pp.112, 2735~2752
- The Asia-Pacific perspective: redefining obesity and its treatment, "World Health Organization", Health Communications, 15~21 (2000)
- Vítek L, "Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels", Atherosclerosis, 160, pp.449~456 (2002)
- Schwertner HA, "Association of low serum concentration of bilirubin with increased risk of coronary artery disease", Clin Chem, 40, pp.18~23 (1994)
- Hopkins PN, "Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease", Arterioscler Thromb Vasc Biol, 16, pp.250~255 (1996)
- Madhavan M, "Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults", Atherosclerosis, 131, pp.107~113 (1997)
- Vítek L, "The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases", Front Pharmacol, 3, pp.55~ (2012)
- Pagano G, "Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association", Hepatology, 35, pp.367~372 (2002)
- Ruhl CE, "Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States", Gastroenterology, 124, pp.71~79 (2003)
- Sanyal AJ, "Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities", Gastroenterology, 120, pp.1183~1192 (2001)
- Wu ML, "A central role of heme oxygenase-1 in cardiovascular protection", Antioxid Redox Signal, 15, pp.1835~1846 (2011)
- Yu J, "Heme oxygenase-1 protects against steatohepatitis in both cultured hepatocytes and mice", Gastroenterology, 138, pp.694~704 (2010)
- Muraca M, "Influence of sex and sex steroids on bilirubin uridine diphosphate-glucuronosyltransferase activity of rat liver", Gastroenterology, 87, pp.308~313 (1984)
