Reproductive Endocrinology

Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease, affecting 10–20% of the total pediatric population, including 8% of non-obese children and 50–80% of those who are obese.

Purpose of the study was to determine the characteristics of vitamin D status in Ukrainian adolescent girls with NAFLD and metabolically unhealthy obesity.

Materials and methods. 120 girls aged 12–17 years with NAFLD and metabolically unhealthy obesity, as well as 180 conditionally somatically healthy girls with normal sexual development and normal body weights (control group) were under observation. The examination set included clinical and anamnestic data, anthropometry, assessment of sexual development, clinical blood test, general urinalysis, coprogram, parasitological examination of feces, electrocardiography, lipid profile, glucose, insulin, HOMA index, alanine aminotransferase, aspartate aminotransferase, total protein, amylase, blood test for markers of hepatitis B, C, autoimmunological studies, ultrasound and elastography of the hepatobiliary system, consultation with an endocrinologist, gastroenterologist, according to the indications - cardiologist, pulmonologist, allergist and other specialists.

Results. A characteristic feature of vitamin D status in adolescent girls with NAFLD and metabolically unhealthy obesity was its deficiency in 65.83% of cases, while in the control deficiency was observed less often 1.5 times – in 43.89 % of patients. The average 25(OH)D level in the group without steatosis was 22.00 ± 0.56 ng/ml, while in patients with NAFLD and metabolically unhealthy obesity it was 1.34 times lower – 16.44 ± 0.73 ng/ml. Conclusion. Correlation analysis showed the role of 25(OH)D deficiency in the development of diffuse liver diseases, disorders of lipid, carbohydrate, and purine metabolism in adolescent girls with NAFLD and obesity, that is requires an adequate correction of the status of this vitamin during treatment.

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9.            Alexander, J., Torbenson, M., Wu, T.T, et al. “Non-alcoholic fatty liver disease contributes to hepatocarcinogenesis in non-cirrhotic liver: a clinical and pathological study.” J Gastroenterol Hepatol 28.5 (2013): 848–54. DOI: 10.1111/jgh.12116

10.          Alterio, A., Alisi, A., Liccardo, D., et al. “Non-alcoholic fatty liver and metabolic syndrome in children: A vicious circle.” Horm Res Paediatr 82 (2014): 283–9. DOI: 10.1159/000365192

11.          Arsik, I., Frediani, J.K., Frezza, D., et al. “Alanine Aminotransferase as a Monitoring Biomarker in Children with Nonalcoholic Fatty Liver Disease: A Secondary Analysis Using TONIC Trial Data.” Children (Basel) 5.6 (2018): 64. DOI: 10.3390/children5060064

12.          Binkley, N., Wiebe, D. “Clinical controversies in vitamin D: 25(OH)D measurement, target concentration, and supplementation.” Journal of clinical densitometry16.4 (2013): 402–8. DOI: 10.1016/j. jocd.2013.08.006

13.          Cashman, K.D., Dowling, K.G., Skrabakova, Z., et al. “Vitamin D deficiency in Europe: pandemic?” The American journal of clinical nutrition 103.4 (2016): 1033–44. DOI: 10.3945/ajcn.115.120873

14.          Centers for Disease Control and Prevention. Defining Childhood Obesity (2018).

15.          Clemente, M.G., Mandato, C., Poeta, M., Vajro, P. “Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.” World J Gastroenterol 22.36 (2016): 8078–93. DOI: 10.3748/wjg. v22.i36.8078

16.          Commission of the European Communities. “Vitamin D.” In: Nutrient and energy intakes of the European Community: report of the Scientific Committee for Food. 31st series. Brussels (Luxembourg). Office of Official Publications of the European Communities (1993): 132–9.

17.          Dowla, S., Pendergrass, M., Bolding, M., et al. “Effectiveness of a carbohydrate restricted diet to treat non-alcoholic fatty liver disease in adolescents with obesity: Trial design and methodology.” Contemp Clin Trials 68 (2018): 95–101. DOI: 10.1016/j.cct.2018.03.014

18.          Eyles, D.W., Smith, S., Kinobe, R., et al. “Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.” J Chem Neuroanat 29.1 (2005): 21–30. DOI: 10.1016/j.jchemneu.2004.08.006

19.          Frommherz, L., Bub, A., Hummel, E., et al. “Age-Related Changes of Plasma Bile Acid Concentrations in Healthy Adults – Results from the Cross-Sectional KarMeN Study”. PLoS ONE 11 (2016): e0153959. DOI: 10.1371/journal.pone.0153959

20.          González-Gross, M., Valtueña, J., Breidenassel, C., et al; HELENA Study Group. “Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by Nutrition in Adolescence study.” Br J Nutr 107.5 (2012): 755–64. DOI: 10.1017/S0007114511003527

21.          Holick, M.F., Chen, T.C., Lu, Z., et al. “Vitamin D and skin physiology: a D-lightful story.” J Bone Miner Res 22.2 (2007): 28–33. DOI: 10.1359/jbmr.07s211

22.          Husmann, C., Frank, M., Schmidt, B., et al. “Low 25(OH)-vitamin D concentrations are associated with emotional and behavioral problems in German children and adolescents”. PLoS One. 2017 Aug 23;12(8):e0183091. DOI: 10.1371/journal.pone.0183091.

23.          Institute of Medicine Food and Nutrition Board. Dietary reference intakes for calcium and vitamin D. Washington (DC). National Academies Press (2011).

24.          Kelsey, M.M., Zaepfel, A., Bjornstad, P., et al. “Age-related consequences of childhood obesity.” Gerontology 60 (2014): 222–8. DOI: 10.1159/000356023

25.          Lawlor, D.A., Callaway, M., Macdonald-Wallis, C., et al. “Nonalcoholic fatty liver disease, liver fibrosis, and cardiometabolic risk factors in adolescence: a cross-sectional study of 1874 general population adolescents.” J Clin Endocrinol Metab 99.3 (2014): 410–7. DOI: 10.1210/jc.2013-3612

26.          Mauz, E., Lange, M., Houben, R., et al.; on behalf of the KiGGS Cohort Research Team. “Cohort profile: KiGGS cohort longitudinal study on the health of children, adolescents and young adults in Germany.” International Journal of Epidemiology 49.2 (2020): 375–375k. DOI: org/10.1093/ije/dyz231

27.          Nobili, V., Alisi, A., Newton, K.P., et al. “Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease.” Gastroenterology 150.8 (2016): 1798–810. DOI: 10.1053/j.gastro.2016.03.009

28.          Pike, J.W., Meyer, M.B., Martowicz, M.L., et al. “Emerging regulatory paradigms for control of gene expression by 1,25-dihydroxyvitamin D3.” The Journal of steroid biochemistry and molecular biology 121.1–2 (2010): 130–5. DOI: 10.1016/j.jsbmb.2010.02.036

29.          Polkowska, G., Polkowski, W., Kudlicka, A., et al. “Range of serum bile acid concentrations in neonates, infants, older children, and in adults.” Med Sci Monit 7 Suppl 1 (2001): 268–70.

30.          Shah, J., Okubote, T., Alkhouri, N. “Overview of Updated Practice Guidelines for Pediatric Nonalcoholic Fatty Liver Disease.” Gastroenterol Hepatol (N Y) 14.7 (2018): 407–14.

31.          Temple, J.L., Cordero, P., Li, J., et al. “A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence.” Int J Mol Sci 17.6 (2016): 947. DOI: 10.3390/ijms17060947

32.          Vieth, R. “Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids.” The Journal of steroid biochemistry and molecular biology 89–90.1–5 (2004): 571–3. DOI: 10.1016/j.jsbmb.2004.03.037

33.          Wallis, D.E., Penckofer, S., Sizemore, G.W. “The "sunshine deficit" and cardiovascular disease.” Circulation 118.14 (2008): 1476–85. DOI: 10.1161/CIRCULATIONAHA.107.713339