Skip to main content

Advertisement

Log in

The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD)

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children.

Methods

Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol.

Results

In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07–10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11–13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28).

Conclusions

We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-health crisis, common sense cure. Lancet. 2002;360:473–82.

    Article  PubMed  Google Scholar 

  2. Gopinath B, Baur LA, Teber E, et al. Effect of obesity on retinal vascular structure in pre-adolescent children. Int J Pediatr Obes. 2011;6(2–2):e353–9.

    Article  PubMed  Google Scholar 

  3. Adams LA, Lindor KD. Nonalcoholic fatty liver disease. Ann Epidemiol. 2007;17(11):863–9.

    Article  PubMed  Google Scholar 

  4. Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7(4):195–203.

    Article  PubMed  Google Scholar 

  5. Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54:700–13.

    Article  PubMed  Google Scholar 

  6. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–9.

    Article  PubMed  Google Scholar 

  7. Hübscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathology. 2006;49:450–65.

    Article  PubMed  Google Scholar 

  8. Brunt EM, Janney CG, Di Bisceglie AM, et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.

    Article  CAS  PubMed  Google Scholar 

  9. Kleiner DE, Brunt EM, van Natta M, et al. Design and validation of a histological scoring system for non-alcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  10. Nobili V, Svegliati-Baroni G, Alisi A, et al. A 360-degree overview of paediatric NAFLD: recent insights. J Hepatol. 2013;58(6):1218–29.

    Article  PubMed  Google Scholar 

  11. Alisi A, Cianfarani S, Manco M, Agostoni C, Nobili V. Non-alcoholic fatty liver disease and metabolic syndrome in adolescents: pathogenetic role of genetic background and intrauterine environment. Ann Med. 2012;44(1):29–40.

    Article  CAS  PubMed  Google Scholar 

  12. Sundaram SS, Zeitler P, Nadeau K. The metabolic syndrome and non-alcoholic fatty liver disease in children. Curr Opin Pediatr. 2009;21:529–35.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Alisi A, Nobili V. Overlapping clinical features between NAFLD and metabolic syndrome in children. EMJ Hepatol. 2014;1:55–61.

    Google Scholar 

  14. Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C. Pediatric non-alcoholic fatty liver disease metabolic syndrome and cardiovascular risk. World J Gastroenterol. 2011;17(26):3082–91.

    PubMed Central  PubMed  Google Scholar 

  15. Wong TY, Barr EL, Tapp RJ, Harper CA, Taylor HR, Zimmet PZ, Shaw JE, et al. Retinopathy in persons with impaired glucose metabolism: the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Am J Ophthalmol. 2005;140:1157–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wong TY, Klein R, Islam FM, et al. Three-year incidence and cumulative prevalence of retinopathy: the Atherosclerosis Risk in Communities study. Am J Ophthalmol. 2007;143:970–6.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Cheung N, Saw SM, Islam FM, et al. BMI and retinal vascular caliber in children. Obesity Silver Spring. 2007;15(1):209–15.

    Article  PubMed  Google Scholar 

  18. Wang JJ, Taylor B, Wong TY, et al. Retinal vessel diameters and obesity: a population-based study in older persons. Obesity (Silver Spring). 2006;14(2):206–14.

    Article  Google Scholar 

  19. Shore AC, Tooke JE. Microvascular function in human essential hypertension. J Hypertens. 1994;12:717–28.

    Article  CAS  PubMed  Google Scholar 

  20. Noon JP, Walker BR, Webb DJ, et al. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest. 1997;99:1873–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Antonios TF, Singer DR, Markandu ND, et al. Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. Hypertension. 1999;34:655–8.

    Article  CAS  PubMed  Google Scholar 

  22. Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HA. Microcirculation in hypertension: a new target for treatment? Circulation. 2001;104:735–40.

    Article  CAS  PubMed  Google Scholar 

  23. Yu T, Mitchell P, Berry G, et al. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol. 1998;16:83–9.

    Article  CAS  Google Scholar 

  24. Wong TY, Klein R, Sharrett AR, et al. The prevalence and risk factors of retinal microvascular abnormalities in older persons: the Cardiovascular Health Study. Ophthalmology. 2003;110:658–66.

    Article  PubMed  Google Scholar 

  25. Klein R, Klein BE, Moss SE, et al. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol. 1994;112:92–8.

    Article  CAS  PubMed  Google Scholar 

  26. Keith NM, Wagener HP, Barker NW. Some different types of essential hypertension: their course and prognosis. Am J Med Sci. 1939;197:332–43.

    Article  Google Scholar 

  27. Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med. 2004;351:2310–7.

    Article  CAS  PubMed  Google Scholar 

  28. Katsi V, Vlachopoulos C, Souretis G, et al. Association between retinal microcirculation and aortic stiffness in hypertensive patients. Int J Cardiol. 2012;157(3):370–3.

    Article  PubMed  Google Scholar 

  29. Leung H, Wang JJ, Rochtchina E, et al. Relationships between age, blood pressure, and retinal vessel diameters in an older population. Invest Ophthalmol Vis Sci. 2003;44(7):2900–4.

    Article  PubMed  Google Scholar 

  30. Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabetes Med. 2007;24:137–44.

    Article  Google Scholar 

  31. Kawasaki R, Wang JJ, Rochtchina E, et al. Cardiovascular risk factors and retinal microvascular signs in an adult Japanese population: the Funagata Study. Ophthalmology. 2006;13:1378–84.

    Article  Google Scholar 

  32. van Leiden HA, Dekker JM, Moll AC, et al. Blood pressure, lipids, and obesity are associated with retinopathy: the Hoorn Study. Diabetes Care. 2002;25:1320–5.

    Article  PubMed  Google Scholar 

  33. De Jongh RT, Serne EH, IJzerman RG, et al. Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation. 2004;109:2529–35.

    Article  PubMed  Google Scholar 

  34. Daniels SR, Lipman MJ, Burke MJ, Loggie JM. The prevalence of retinal vascular abnormalities in children and adolescents with essential hypertension. Am J Ophthalmol. 1991;111:205–8.

    Article  CAS  PubMed  Google Scholar 

  35. Skalina ME, Annable WL, Kliegman RM, Fanaroff AA. Hypertensive retinopathy in the newborn infant. J Pediatr. 1983;103:781–6.

    Article  CAS  PubMed  Google Scholar 

  36. Băloşeanu CL, Streba CT, Vere CC, Comănescu V, Rogoveanu I. Association between liver histology, carotid ultrasonography and retinal vascular changes in patients with nonalcoholic fatty liver disease (NAFLD). Rom J Morphol Embryol. 2012;53(3):609–14.

    PubMed  Google Scholar 

  37. Centers for Disease Control and Prevention. About BMI for children and teens [cited 2013 Jul 13]. Available http://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html.

  38. Cole TJ, Freeman JV, Preece MA. Body mass index reference curves for the UK, 1990. Arch Dis Childhood. 1995;73:25–9.

    Article  CAS  Google Scholar 

  39. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.

    Article  CAS  PubMed  Google Scholar 

  40. Giordano U, Della CC, Cafiero G, et al. Association between nocturnal blood pressure dipping and insulin resistance in children affected by NAFLD. Eur J Pediatr. 2014;173(11):1511–8.

    Article  PubMed  Google Scholar 

  41. Taarnhoj NCBB, Munch IC, Sander B, et al. Straight versus tortuous retinal arteries in relation to blood pressure and genetics. Br J Ophthalmol. 2008;92:1055–60.

    Article  CAS  PubMed  Google Scholar 

  42. Wilkinson CP, Ferris FL, Klein RE, et al. Global diabetic retinopathy project group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677–82.

    Article  CAS  PubMed  Google Scholar 

  43. Brunner EJ, Shipley MJ, Witte DR, et al. Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study. Diabetes Care. 2006;29:26–31.

    Article  PubMed  Google Scholar 

  44. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria: the DECODE study group: European Diabetes Epidemiology Group: Diabetes Epidemiology: Collaborative analysis of diagnostic criteria in Europe. Lancet. 1999;354:617–21.

  45. Gu D, Wildman RP, Wu X, et al. Incidence and predictors of hypertension over 8 years among Chinese men and women. J Hypertens. 2007;25:517–23.

    Article  CAS  PubMed  Google Scholar 

  46. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  PubMed  Google Scholar 

  47. Targher G, Bertolini L, Padovani R, et al. Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care. 2004;27(10):2498–500.

    Article  PubMed  Google Scholar 

  48. Targher G, Bertolini L, Padovani R, et al. Associations between liver histology and carotid intima-media thickness in patients with nonalcoholic fatty liver disease. Arterioscler Thromb Vasc Biol. 2005;25(12):2687–8.

    Article  CAS  PubMed  Google Scholar 

  49. Nguyen TT, Wang JJ, Wong TY. Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications. Diabetes Care. 2007;30(10):2708–15.

    Article  PubMed  Google Scholar 

  50. Wong TY, Mitchell P. The eye in hypertension. Lancet. 2007;369(9559):425–35.

    Article  PubMed  Google Scholar 

  51. Gopinath B, Baur LA, Wang JJ, et al. Blood pressure is associated with retinal vessel signs in preadolescent children. J Hypertens. 2010;28(7):1406–12.

    Article  CAS  PubMed  Google Scholar 

  52. Manco M, et al. Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease. Atherosclerosis. 2010;209:463–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The following authors were involved in the different stages of manuscript writing: study guarantor: V.N; study concept and design: V.N., D.L., L.B, A.M; acquisition of clinical data: D.L., A.M, S.P, P.V, U.G, A.G.A.M, S.P, L.B, V.N and drafting of the manuscript: D.L, A.M, L.B, V.N. No authors received any funding for this manuscript. All the authors certify to have participated sufficiently in the conception and design of this work as well as in the writing of the manuscript to take public responsibility for it. Neither this manuscript nor one with substantially similar content under our authorship has been published or is being considered for publication elsewhere. If requested, we will produce the data on which the manuscript is based for examination by the editors or their assignees.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Valerio Nobili.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liccardo, D., Mosca, A., Petroni, S. et al. The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD). J Gastroenterol 50, 903–912 (2015). https://doi.org/10.1007/s00535-014-1024-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-014-1024-1

Keywords

Navigation