Vitamin D and non-alcoholic fatty liver disease in children

Česká verze

Authors: T. Kráľová ¹ ; Pršo M. ¹; Čierny D. ²; Michnová Z. ¹; Havlíčeková Z. ¹; Kostková M. ¹
Authors place of work: Klinika detí a dorastu JLF UK a UN Martin ¹; Ústav klinickej biochémie JLF UK v Martine ²
Published in the journal: Gastroent Hepatol 2021; 75(4): 335-343
Category: Dětská gastroenterologie: původní práce
doi: https://doi.org/10.48095/ccgh2021335

Summary

Background: Insulin resistance (IR) plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Hypovitaminosis D is associated with several diseases, including hepatic steatosis and obesity. Vitamin D (VD) affects insulin secretion and improves tissue sensitivity to insulin, suggesting that hypovitaminosis D is also associated with IR. The leptin-to-adiponectin ratio (LAR) was investigated as a new marker of IR. Aim: The aim of our study was to determine the association between the VD status, NAFLD and IR in paediatric overweight or obese patients. Methods: The study ran from January 2018 to August 2020 and included 100 subjects. We measured their anthropometric parameters, determined their basic laboratory parameters and the level of leptin and adiponectin, calculated BMI, WHR, WHtR, LAR and HOMA-IR. We measured the degree of hepatic steatosis by obtaining the hepatorenal index (HRI) using ultrasonography, and used real-time elastography to determine the elasticity of the liver parenchyma (LFI). Subsequently, we compared the groups of patients with and without hepatic steatosis and looked for correlations in relation to the level of VD and IR. Results: 4.4% of patients had a severe VD deficiency, 55% of the children had hypovitaminosis D, 28.6% had VD insufficiency and 12% of patients had sufficient VD levels. Patients with significant hepatic steatosis (HRI 1.5 and more) had the lowest level of VD (16.61 ±5.62 μg/l, P = 0.015). The level of VD in patients with hepatic steatosis was inversely correlated with waist circumference, hip circumference, height, weight, triacylglycerols, GMT, C-peptide, insulin, HOMA-IR, HRI and LFI. Leptin levels were highest in patients with hepatic pre-steatosis. LAR was highest in the group with hepatic steatosis, but we did not observe significant correlations in relation to other parameters. Conclusion: VD levels are inversely associated with the degree of hepatic steatosis in overweight or obese paediatric patients. HOMA-IR inversely correlates with VD levels and positively with LFI. The LAR value was highest in the group of patients with steatosis, although we did not find out any significant correlations in relation to VD status and HRI.

Keywords:

vitamin D – non-alcoholic fatty liver disease – insulin resistance – leptin – Adiponectin – obesity – childhood

Zdroje

1. Pludowski P, Holick MF, Grant WB et al. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 2018; 175: 125–135. doi: 10.1016/j.jsbmb.2017.01.021.

2. Nosáková L, Bánovčin P, Pindura M et al. Prevalencia hypovitaminózy D a poruchy glukózovej tolerancie u pacientov s neuroendokrinnými tumormi podstupujúcich liečbu somatostatínovými analógmi. Gastroent Hepatol 2020; 74 (5): 410–414. doi: 10.14735/amgh2020410.

3. Ayina CN, Endomba FT, Mandengue SH et al. Association of the leptin-to-adiponectin ratio with metabolic syndrome in a sub-Saharan African population. Diabetol Metab Syndr 2017; 9 (1): 66. doi: 10.1186/s13098-017- 0265-6.

4. Siebert T, Malachovský I, Statelová D et al. Motivational interviewing for improving periodontal health. Bratisl Lek Listy 2020; 121 (9): 670–674. doi: 10.4149/BLL_2020_110.

5. Brůha R, Dvořák K, Fejfar T et al. Doporučený postup České hepatologické společnosti ČLS JEP pro diagnostiku a léčbu nealkoholové tukové choroby jater. Gastroent Hepatol 2020; 74 (2): 103–110. doi: 10.14735/amgh2020103.

6. Cimini FA, Barchetta I, Carotti S et al. Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease. World J Gastroenterol 2017; 23 (19): 3407–3417. doi: 10.3748/wjg.v23.i19.3407.

7. Shah J, Okubote T, Alkhouri N. Overview of updated practice guidelines for pediatric nonalcoholic fatty liver disease. Gastroenterol Hepatol 2018; 14 (7): 407–414.

8. Fedelešová M, Kupčová V, Szántová M et al. Možnosti použitia neinvazívnych metód pri nealkoholovej tukovej chorobe pečene. Gastroent Hepatol 2017; 71 (4): 325–332. doi: 10.14735/amgh2017325.

9. Pršo M, Kozár M, Kráľová T et al. Ultrasonografické hodnotenie steatózy pečene u obéznych pediatrických pacientov. Gastroent Hepatol 2018; 72 (6): 473–478. doi: 10.14735/amgh2018473.

10. Michnová Z, Pršo M, Zúbriková L et al. Diagnostika ložiskových lézí jater u dětí s využitím kontrastní ultrasonografie. Gastroent Hepatol 2019; 73 (6): 481–487. doi: 10.14735/amgh2019481.

11. Serai SD, Panganiban J, Dhyani M et al. Imaging modalities in pediatric NAFLD. Clin Liver Dis 2021; 17 (3): 200–208. doi: 10.1002/cld.994.

12. Eliades M, Spyrou E. Vitamin D: a new player in non-alcoholic fatty liver disease? World J Gastroenterol 2015; 21 (6): 1718–1727. doi: 10.3748/wjg.v21.i6.1718.

13. Chen LW, Chien CH, Kuo SF et al. Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: a community-based study. BMC Gastroenterol 2019; 19 (1): 126. doi: 10.1186/s12876-019-1040-y.

14. Angın Y, Arslan N, Kuralay F. Leptin-to-adiponectin ratio in obese adolescents with nonalcoholic fatty liver disease. Turk J Pediatr 2014; 56 (3): 259–266.

15. Cole TJ, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes 2012; 7 (4): 284–294. doi: 10.1111/j.2047-6310.2012.00064.x.

16. Zimmet P, Alberti KG, Kaufman F et al. IDF Consensus Group. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 2007; 8 (5): 299–306. doi: 10.1111/j.1399-5448.2007.00271.x.

17. WHO. Waist circumference and waist-hip ratio. 2008 [online]. Available from: http: //apps.who.int/iris/bitstream/handle/10665/44583/ 9789241501491_eng.pdf; jsessionid=F20C447A 6049B0A6E960C774A000F65A?sequence=1.

18. Rambhojan C, Larifla L, Clepier J et al. Vitamin D status, insulin resistance, leptin-to-adiponectin ratio in adolescents: results of a 1-year lifestyle intervention. Open Access Maced J Med Sci 2016; 4 (4): 596–602. doi: 10.3889/oamjms.2016.131.

19. Webb M, Yeshua H, Zelber-Sagi S et al. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol 2009; 192 (4): 909–914. doi: 10.2214/AJR.07.4016.

20. Račanská E. Vitamín D – hormón, ktorý nám chýba. Prakt lekárn 2014; 4 (2–3): 53–55.

21. Zhai HL, Wang NJ, Han B et al. Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)). Br J Nutr 2016; 115 (8): 1352–1359. doi: 10.1017/S0007114516000386.

22. Manco M, Ciampalini P, Nobili V. Low levels of 25-hydroxyvitamin D (3) in children with biopsy-proven nonalcoholic fatty liver disease. Hepatology 2010; 51 (6): 2229. doi: 10.1002/hep.23 724.

23. Nelson JE, Roth CL, Wilson LA et al. Vitamin D deficiency is associated with increased risk of non-alcoholic wteatohepatitis in adults with non-alcoholic fatty liver disease: possible role for MAPK and NF-kB? Am J Gastroenterol 2016; 111 (6): 852–863. doi: 10.1038/ajg.2016.51.

24. Nier A, Huber Y, Labenz C et al. Adipokines and endotoxemia correlate with hepatic steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients 2020; 12 (3): 699. doi: 10.3390/nu12030699.

25. Ramírez-Vélez R, González-Ruíz K, González-Jiménez E et al. Serum leptin as a mediator of the influence of insulin resistance on hepatic steatosis in youths with excess adiposity. Nutr Metab Cardiovasc Dis 2021; 31 (4): 1308–1316. doi: 10.1016/j.numecd.2020.12.014.

26. Małecki P, Mania A, Tracz J et al. Adipocytokines as risk factors for development of nonalcoholic fatty liver disease in children. 2021 [online]. Avaible from: https: //www.sciencedirect.com/science/article/abs/pii/S0973688321000 542.

27. Mikami K, Endo T, Sawada N et al. Leptin/adiponectin ratio correlates with hepatic steatosis but not arterial stiffness in nonalcoholic fatty liver disease in Japanese population. Cytokine 2020; 126: 154927. doi: 10.1016/j.cyto.2019.154927.

28. Dasarathy J, Varghese R, Feldman A et al. Patients with nonalcoholic fatty liver disease have a low response rate to vitamin D supplementation. J Nutr 2017; 147 (10): 1938–1946. doi: 10.3945/jn.117.254292.

29. Gad AI, Elmedames MR, Abdelhai AR et al. Efficacy of vitamin D supplementation on adult patients with non-alcoholic fatty liver disease: a single-center experience. Gastroenterol Hepatol Bed Bench 2021; 14 (1): 44–52.

30. Sakpal M, Satsangi S, Mehta M et al. Vitamin D supplementation in patients with nonalcoholic fatty liver disease: a randomized controlled trial. JGH Open 2017; 1 (2): 62–67. doi: 10.1002/jgh3.12010.