본문 바로가기
KERD
논문KCI 등재

Hepcidin Levels and Pathological Characteristics in Children with Fatty Liver Disease

0

조회

0

다운로드

1

인용

0

참고문헌

키워드

주제분류소아과학

초록

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6–17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gammaglutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

Abstract

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6–17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gammaglutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

참고문헌 (39)

  1. American Gastroenterological Association, "American Gastroenterological Association medical position statement : nonalcoholic fatty liver disease", Gastroenterology, 123, pp.1702~1704 (2002)
  2. Neuschwander-Tetri BA, "Nonalcoholic steatohepatitis : summary of an AASLD single topic conference", Hepatology, 37, pp.1202~1219 (2003)
  3. Adams LA, "The natural history of nonalcoholic fatty liver disease : a population-based cohort study", Gastroenterology, 129, pp.113~121 (2005)
  4. Eguchi Y, "JSG-NAFLD. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study", J Gastroenterol, 47, pp.586~595 (2012)
  5. Moran JR, "Steatohepatitis in obese children : a cause of chronic liver dysfunction", Am J Gastroenterol, 78, pp.374~377 (1983)
  6. Chalasani N, "The diagnosis and management of nonalcoholic fatty liver disease : practice guidance from the American Association for the Study of Liver Diseases", Hepatology, 67, pp.328~357 (2018)
  7. Anderson EL, "The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis", PLoS One, 10, pp.e0140908~ (2015)
  8. Schwimmer JB, "Prevalence of fatty liver in children and adolescents", Pediatrics, 118, pp.1388~1393 (2006)
  9. Tominaga K, "Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey", Dig Dis Sci, 40, pp.2002~2009 (1995)
  10. Park HS, "Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents", Am J Clin Nutr, 82, pp.1046~1051 (2005)
  11. Milic S, "The role of iron and iron overload in chronic liver disease", Med Sci Monit, 22, pp.2144~2151 (2016)
  12. Zhao N, "Iron regulation by hepcidin", J Clin Invest, 123, pp.2337~2343 (2013)
  13. Ramos E, "Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis", Blood, 120, pp.3829~3836 (2012)
  14. Ahmed U, "Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis", World J Gastroenterol, 18, pp.4651~4658 (2012)
  15. Messner DJ, "Iron overload causes oxidative stress and impaired insulin signaling in AML-12 hepatocytes", Dig Dis Sci, 58, pp.1899~1908 (2013)
  16. Nelson JE, "Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease", Hepatology, 53, pp.448~457 (2011)
  17. Chalasani N, "The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association", Am J Gastroenterol, 107, pp.811~826 (2012)
  18. Matteoni CA, "Nonalcoholic fatty liver disease : a spectrum of clinical and pathological severity", Gastroenterology, 116, pp.1413~1419 (1999)
  19. Kleiner DE, "Design and validation of a histological scoring system for nonalcoholic fatty liver disease", Hepatology, 41, pp.1313~1321 (2005)
  20. Brunt EM, "Nonalcoholic steatohepatitis : a proposal for grading and staging the histological lesions", Am J Gastroenterol, 94, pp.2467~2474 (1999)
  21. Park CH, "Hepcidin, a urinary antimicrobial peptide synthesized in the liver", J Biol Chem, 276, pp.7806~7810 (2001)
  22. Leong WI, "Hepcidin, the recently identified peptide that appears to regulate iron absorption", J Nutr, 134, pp.1~4 (2004)
  23. Vuppalanchi R, "Serum hepcidin levels are associated with obesity but not liver disease", Obesity(Silver Spring), 22, pp.836~841 (2014)
  24. Cakir M, "Hepcidin levels in children with chronic liver disease", Saudi J Gastroenterol, 21, pp.300~305 (2015)
  25. Takahashi Y, "Histopathological characteristics of nonalcoholic fatty liver disease in children : comparison with adult cases", Hepatol Res, 41, pp.1066~1074 (2011)
  26. Schwimmer JB, "Histopathology of pediatric nonalcoholic fatty liver disease", Hepatology, 42, pp.641~649 (2005)
  27. Lee P, "Regulation of hepcidin transcription by interleukin-1 and interleukin-6", Proc Natl Acad Sci U S A, 102, pp.1906~1910 (2005)
  28. Tomosugi N, "The discovering of hepcidin and following develop", Nihon Naika Gakkai Zasshi, 99, pp.1180~1187 (2010)
  29. Gardenghi S, "Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus", Blood, 123, pp.1137~1145 (2014)
  30. Verga Falzacappa MV, "STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation", Blood, 109, pp.353~358 (2007)
  31. Datz C, "Iron homeostasis in the metabolic syndrome", Eur J Clin Invest, 43, pp.215~224 (2013)
  32. Chung B, "Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells", J Nutr, 137, pp.2366~2370 (2007)
  33. Aigner E, "Pathways underlying iron accumulation in human nonalcoholic fatty liver disease", Am J Clin Nutr, 87, pp.1374~1383 (2008)
  34. Barisani D, "Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload", J Hepatol, 49, pp.123~133 (2008)
  35. Aigner E, "Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver", World J Hepatol, 7, pp.177~188 (2015)
  36. Rockey DC, "Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing", J Clin Invest, 98, pp.1381~1388 (1996)
  37. Han CY, "Hepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt", Nat Commun, 7, pp.13817~ (2016)
  38. Mitsuyoshi H, "Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease", Hepatol Res, 39, pp.366~373 (2009)
  39. Bekri S, "Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH", Gastroenterology, 131, pp.788~796 (2006)

관련 논문AI추천

The Clinical Significance of Serum Ferritin in Pediatric Non-Alcoholic Fatty Liver Disease고홍, 김승, 강윤구, 나지훈, 박소원대한소아소화기영양학회 · Pediatric Gastroenterology, Hepatology & Nutrition2014 · 제17권 제4호Pathologic Impact of Insulin Resistance and Sensitivity on the Severity of Liver Histopathology in Pediatric Non-Alcoholic Steatohepatitis김용주, 김자혜, 문진화, 박병한, 윤정민, 이영호, 장세민연세대학교의과대학 · Yonsei Medical Journal2017 · 제58권 제4호Serologic Biomarkers for Hepatic Fibrosis in Obese Children with Nonalcoholic SteatohepatitisHye Ran Yang, In Hyuk Yoo, Jung Yeon Joo대한소아소화기영양학회 · Pediatric Gastroenterology, Hepatology & Nutrition2024 · 제27권 제4호Serum prohepcidin levels in chronic hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease김나영, 김진욱, 박영수, 이동호, 이상협, 정숙향, 황진혁대한간학회 · Clinical and Molecular Hepatology2010 · 제16권 제3호Low Serum Potassium Levels Associated with Disease Severity in Children with Nonalcoholic Fatty Liver DiseaseAdam Tabbaa, Kazem Hoshemand, Mina Shaker, Naim Alkhouri, Rocio Lopez, Valerio Nobili대한소아소화기영양학회 · Pediatric Gastroenterology, Hepatology & Nutrition2015 · 제18권 제3호Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in ChildrenAtike Atalay, Aygen Yılmaz, Cihat Aksoy, Gulsah Kaya Aksoy, Reha Artan, Sebahat Özdem대한소아소화기영양학회 · Pediatric Gastroenterology, Hepatology & Nutrition2019 · 제22권 제5호

이 간행물의 다른 논문 (8건)