Relationships with Alanine Aminotransferase Activity, and Anthropometric and Biochemical Measures in Obese Children

단순 비만아에서 간효소치와 신체 계측 및 생화학 측정치와의 관련성

  • Yun, Gyoung-Bin (Department of Pediatrics, Chungnam National University, School of Medicine) ;
  • Kim, Jae-Young (Department of Pediatrics, Chungnam National University, School of Medicine)
  • 윤경빈 (충남대학교 의학전문대학원 소아과학교실) ;
  • 김재영 (충남대학교 의학전문대학원 소아과학교실)
  • Received : 2009.01.23
  • Accepted : 2009.03.09
  • Published : 2009.03.30

Abstract

Purpose: To investigate the physical and biochemical parameters related with elevated serum alanine aminotransferase (ALT) levels in obese children. Methods: One hundred forty-two obese or overweight children who visited the out-patient clinics of Chungnam National University Hospital between January 2006 and August 2008 were enrolled. Physical measures and biochemical tests were performed in all patients. Liver sonography was performed in 43 patients. They were divided into the following 2 groups based on ALT levels: group I, normal ALT levels (n=65); and group II, elevated ALT levels (n=77). We compared the physical measures, biochemical results, and ultrasonographic findings of the livers in both groups. Other causes of elevated serum ALT levels were ruled out. Results: The male-to-female ratios were 1.6:1 in group I and 7.6:1 in group II. Among physical parameters, the waist circumference-to-height ratio and hip circumference-to-height ratio were significantly higher in group II (p=0.001 and 0.046, respectively). Among biochemical parameters, aspartate aminotransferase (AST), ${\gamma}$-glutamyltransferase (${\gamma}$-GT), and total cholesterol levels were significantly higher in group II (p<0.001, 0.001, and 0.001, respectively). The AST/ALT ratio was <1 (mean, 0.55) and statistically lower in group II. There was a positive correlation between the serum ALT level and ${\gamma}$-GT (p<0.001, r=0.750), and a positive correlation between the serum ALT level and the waist circumference-to-height ratio in group II (p<0.001, r=0.401). Conclusion: The results suggest that the waist circumference-to-height ratio and ${\gamma}$-GT may be associated with elevated alanine aminotransferase activity in obese children.

목 적: 비만에서 발생하는 비알코올성 지방간질환은 대부분 무증상이어서 혈청 검사에서 간효소치 상승이 있거나 간초음파검사에서 지방간이 발견되는 경우에 이 질환에 대한 의학적 관심이 증가한다. 본 연구에서는 비만아와 과체중아에서 간세포손상을 반영하는 ALT 상승과 신체 계측치 및 생화학적 검사치들과의 관련성을 알아보고자 하였다. 방 법: 2006년 1월부터 2008년 6월까지 충남대병원 소아청소년과에서 비만 또는 과체중으로 진단받은 142예를 대상으로 신체 계측, 생화학 검사를, 간초음파검사는 일부 환자에서 시행하였다. ALT치를 기준으로 정상 군(I군)과 상승 군(II군)으로 분류하여 신체 계측치, 생화학 검사치, 간초음파 소견을 비교하였다. 바이러스간염, 약물 유발 간염, 대사이상 간염, 내분비 장애, 유전 질환이 있는 경우는 연구 대상에서 제외하였다. 결 과: 단순 비만아에서 간전이효소치의 상승은 전체의 54.2%에서 있었으며, 남녀별로는 남아 63.0%, 여아 26.5%에서 있었다. I군과 II군의 나이는 각각 11.4${\pm}$3.3, 11.7${\pm}$3.2세로 차이가 없었다. 성별 분포는 I군은 남아 40예, 여아 25예로 총 65예, II군은 남아 68예, 여아 9예로 총 77예로 양군 모두 남아가 통계적으로 유의하게 많았으며(p=0.003, 0.001) 남녀 비는 I군 1.6:1, II군 7.6:1로 II군에서 남아의 발생빈도가 4.8배 더 높았다. 신체 계측치는 허리둘레/키 비, 엉덩이둘레/키 비가 II군에서 통계적으로 유의하게 높았으며(p=0.001, 0.046), 키, 체중, 체질량지수, 허리둘레, 엉덩이둘레, 허리둘레/엉덩이둘레 비, 비만 정도는 양 군 간에 유의한 차이가 없었다. 생화학 검사치와 인슐린 저항성에서는 AST, ${\gamma}$-GT, 총콜레스테롤 수치가 II군에서 통계적으로 유의하게 높았고, AST/ALT비는 I군 1.10${\pm}$0.41, II군 0.55${\pm}$0.17로 II군에서 유의하게 낮았다(p<0.001, <0.001, <0.001). 중성지방, 고밀도지질단백 콜레스테롤, 저밀도지질단백 콜레스테롤 수치, 공복 시 인슐린 농도, 혈당, 인슐린 저항성 지표는 두 군 간에 통계적으로 유의한 차이가 없었다. 단변량 상관관계분석에서는 체질량지수, 엉덩이둘레/키 비, 허리둘레/키 비, ${\gamma}$-GT, 중성지방이 양의 상관관계를 보였다. 간초음파검사는 I군 11예, II군 32예에서 시행되었는데, 양 군 모두 경도의 지방간 소견이 가장 많았으며, 양 군 간에 지방간 빈도에는 통계적으로 유의한 차이가 없었다. 결 론: 비만아에서 허리둘레/키 비, AST, AST/ALT비, ${\gamma}$-GT, 총 콜레스테롤 농도가 ALT치가 정상인 군 보다 상승된 군에서 통계적으로 유의한 차이를 보였으며, 허리둘레/키 비와 ${\gamma}$-GT가 ALT 상승과 통계적으로 유의한 양의 상관관계를 보여 쉽게 측정할 수 있는 신체 계측치인 허리둘레/키 비를 ALT치가 상승된 비만아의 관리에 참고 자료로 이용해 볼 수 있겠다. 그러나 이에 대해서는 향후 더 많은 연구가 필요하다.

Keywords

References

  1. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2008;48:1-12. https://doi.org/10.1002/hep.22373
  2. Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008;48:119-28. https://doi.org/10.1002/hep.22336
  3. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31. https://doi.org/10.1056/NEJMra011775
  4. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123: 134-40. https://doi.org/10.1053/gast.2002.34168
  5. Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis- Arch Pathol Lab Med 2008;132:1761-6.
  6. Manco M, Bedogni G, Marcellini M, Devito R, Ciampalini P, Sartorelli MR, et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut 2008;57:1283-7. https://doi.org/10.1136/gut.2007.142919
  7. Utzschneider KM, Kahn SE. Review: The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006;91:4753-61. https://doi.org/10.1210/jc.2006-0587
  8. Kim CH, Younossi ZM. Nonalcoholic fatty liver disease:a manifestation of the metabolic syndrome. Cleve Clin J Med 2008;75:721-8. https://doi.org/10.3949/ccjm.75.10.721
  9. Boppidi H, Daram SR. Nonalcoholic fatty liver disease:hepatic manifestation of obesity and the metabolic syndrome. Postgrad Med 2008;120:E1-7.
  10. Papandreou D, Rousso I, Mavromichalis I. Update on non-alcoholic fatty liver disease in children. Clin Nutr 2007;26:409-15. https://doi.org/10.1016/j.clnu.2007.02.002
  11. Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, Papademetris X, et al. Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 2006;91:4287-94. https://doi.org/10.1210/jc.2006-1010
  12. Kral JG, Schaffner F, Pierson RN Jr, Wang J. Body fat topography as an independent predictor of fatty liver. Metabolism 1993;42:548-51. https://doi.org/10.1016/0026-0495(93)90210-F
  13. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450-5. https://doi.org/10.1016/S0002-9343(99)00271-5
  14. Oh SY, Cho YK, Kang MS, Yoo TW, Park JH, Kim HJ, et al. The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease. Metabolism 2006;55:1604-9. https://doi.org/10.1016/j.metabol.2006.07.021
  15. Hubscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathology 2006;49:450-65. https://doi.org/10.1111/j.1365-2559.2006.02416.x
  16. Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008;28:13-24. https://doi.org/10.1111/j.1365-2036.2008.03703.x
  17. American Gastroenterological Association. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology 2002;123:1702-4. https://doi.org/10.1053/gast.2002.36569
  18. Westerbacka J, Cornér A, Tiikkainen M, Tamminen M, Vehkavaara S, Häkkinen AM, et al. Women and men have similar amounts of liver and intra-abdominal fat, despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk. Diabetologia 2004;47:1360-9.
  19. Sartorio A, Del Col A, Agosti F, Mazzilli G, Bellentani S, Tiribelli C, et al. Predictors of non-alcoholic fatty liver disease in obese children. Eur J Clin Nutr 2007;61:877-83. https://doi.org/10.1038/sj.ejcn.1602588
  20. Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC, et al. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997;42:1428-32. https://doi.org/10.1023/A:1018850223495
  21. Bergomi A, Lughetti L, Corciulo N. Italian multicenter study on liver damage in pediatric obesity. Int Obes Relat Metab Disord 1998;22(Suppl):22S.
  22. Louthan MV, Theriot JA, Zimmerman E, Stutts JT, McClain CJ. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. J Pediatr Gastroenterol Nutr 2005;41:426-9. https://doi.org/10.1097/01.mpg.0000177314.65824.4d
  23. Strauss RS, Barlow SE, Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr 2000;136:727-33. https://doi.org/10.1067/mpd.2000.102940
  24. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 2005;115:e561-5. https://doi.org/10.1542/peds.2004-1832
  25. Kinugasa A, Tsunamoto K, Furukawa N, Sawada T, Kusunoki T, Shimada N. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gastroenterol Nutr 1984;3:408-14. https://doi.org/10.1097/00005176-198406000-00018
  26. Kawasaki T, Hashimoto N, Kikuchi T, Takahashi H, Uchiyama M. The relationship between fatty liver and hyperinsulinemia in obese Japanese children. J Pediatr Gastroenterol Nutr 1997;24:317-21. https://doi.org/10.1097/00005176-199703000-00015
  27. Tazawa Y, Noguchi H, Nishinomiya F, Takada G. Serum alanine aminotransferase activity in obese children. Acta Pediatr 1997;86:238-41. https://doi.org/10.1111/j.1651-2227.1997.tb08881.x
  28. Zou CC, Liang L, Hong F, Fu JF, Zhao ZY. Serum adiponectin, resistin levels and non-alcoholic fatty liver disease in obese children. Endocr J 2005;52:519-24. https://doi.org/10.1507/endocrj.52.519
  29. Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK, et al. Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord 2004;28:1257-63. https://doi.org/10.1038/sj.ijo.0802734
  30. Yoo JS, Lee SY, Kim KN, Yoo SM, Sung EJ, Yim JE. Relationship between insulin resistance and serum alanine aminotransferase as a surrogate of NAFLD (nonalcoholic fatty liver disease) in obese Korean children. Diabetes Res Clin Pract 2008;81:321-6. https://doi.org/10.1016/j.diabres.2008.05.006
  31. Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J Pediatr 1995;127:700-4. https://doi.org/10.1016/S0022-3476(95)70156-7
  32. Park JY, Ko JS, Seo JK, Lee R, Shin CH, Kang GH, et al. Nonalcoholic fatty liver disease progressing to cirrhosis in an obese boy with hypopituitarism. Korean J Pediatr Gastroenterol Nutr 2008;2:204-13.
  33. Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004;53:413-9. https://doi.org/10.1136/gut.2003.027581
  34. Tazawa Y, Noguchi H, Nishinomiya F, Takada G. Effect of weight reduction on serum transaminase activities in children with simple obesity. J Pediatr 1996;128:587-8.
  35. Uslan I, Acarturk G, Karaca E, Albayrak R, Yuksel S, Colbay M, et al. The effects of weight loss on normal transaminase levels in obese patients. Am J Med Sci 2007;334:327-30. https://doi.org/10.1097/MAJ.0b013e3181557702
  36. Vajro P, Fontanella A, Perna C, Orso G, Tedesco M, De Vincenzo A. Persistent hyperaminotransferasemia resolving after weight reduction in obese children. J Pediatr 1994;125:239-41. https://doi.org/10.1016/S0022-3476(94)70202-0
  37. Palmer M, Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990;99:1408-13. https://doi.org/10.1016/0016-5085(90)91169-7