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Egyptian Liver Journal
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Evaluation of micronutrients among pediatric liver cirrhosis in Shiraz, Iran

Egyptian Liver Journal volume 12, Article number: 18 (2022) Cite this article

Abstract

Background

Cirrhosis is the final result of most types of liver disease. Zinc, magnesium, and vitamin D have a significantly vital role in the immunologic and physiologic mechanisms in the body. The current study aimed to measure magnesium, zinc, and vitamin D level among children with liver cirrhosis.

Results

One hundred cases were included in the current study. Vitamin D deficiency was found in 53% of the cases. Zinc deficiency was present in 23% of the cases. The magnesium level was more than the normal level among 99% of the cases. There is a significant inverse correlation between zinc level and PELD score (Pearson correlation = − 0.314, P = 0.007).

Conclusion

Zinc deficiency and vitamin D deficiency were seen in children with liver cirrhosis. Serum magnesium level in children with liver cirrhosis was higher than standard. A significant correlation was seen between zinc level and PELD score.

Backgrounds

The liver is the primary organ for metabolism. Liver disease has a profound effect on protein and energy metabolism [1, 2]. Cirrhosis of the liver has several etiology including biliary atresia, Wilson’s disease, and autoimmune hepatitis [3]. Zinc is an essential trace element with various biological actions [4]. In patients with hepatic encephalopathy, zinc deficiency may have a role. Zinc supplementation for the treatment of hepatic encephalopathy was proposed in the literature [5,6,7]. Magnesium deficiency was reported among 30% of children with liver disease [8]. Vitamin D deficiency is an independent risk factor for infection among children with cirrhosis [9]. There are limited studies about zinc, magnesium, and vitamin D deficiencies among children with liver cirrhosis. This study aimed to evaluate the level of zinc, magnesium, and vitamin D among children with liver cirrhosis.

Methods

In this cross-sectional study, all children aged less than 18 years with liver cirrhosis who visited at Pediatric Gastroenterology and Hepatology Clinic of Shiraz University of Medical Sciences were included. The duration of the study was 2 years starting from February 2017. Children with a history of zinc, magnesium, and vitamin D supplementation before the diagnosis of cirrhosis were excluded from the study. Cirrhosis was confirmed after liver biopsy in children using the clinical and radiologic criteria for liver biopsy. For zinc, magnesium, and vitamin D measurement; 5 ml of blood sample was obtained. Zinc and magnesium level measurement was done using atomic absorption spectrometry. Normal zinc level was considered to be 50–150 mcg/dl. The normal level of magnesium was considered to be 0.8–1 mmol/dl. The normal level of vitamin D was considered to be 20–100 ng/dl. In the current study, standard levels of zinc, magnesium, and vitamin D were used for comparison as control.

This study was approved by the ethical committee of the Shiraz University of Medical Sciences. An informed consent form was signed by parents. SPSS ver 25.0 was used for data analysis. The chi-square test was used for comparison.

Results

In the current study, 100 children (m = 52, f = 48) aged less than 18 years were finally included. The mean age of the cases was 7.17 ± 4.84 (min = 5 months, max = 18 years) years with a median age was 6.0 years. Biliary atresia and progressive familial intrahepatic cholestasis were the most frequent etiology of liver cirrhosis among our cases (Table 1).

Table 1 Etiology of liver cirrhosis
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Hepatic encephalopathy was seen in 2% (n = 2) of the cases. Among 2 children with hepatic encephalopathy, one child had zinc deficiency.

Ascites were the most common finding among children with liver cirrhosis and were seen in 21% of children. Among the children, 10% had a history of gastrointestinal bleeding.

The mean of albumin was 3.681 with minimum and maximum levels of 1.2 g/dl and 4.5 g/dl, respectively. Among 69% of cases, the albumin level was in the normal range. Among 31% of the cases, the albumin level was lower than the normal range.

INR was normal among 59% of children with liver cirrhosis. The mean of INR was 1.334, and the median was 1.1 (min = 0.94, max = 4.7) (Table 2).

Table 2 Liver function test among children with liver disease
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The minimum and maximum of serum Na were 128 and 158, respectively. The mean of serum Na was 137.9 meq/dl.

PELD score was used for 89% of the children. Among 31% of children, the PELD score was 1. The MELD score was used for 11% of children. The minimum and maximum MELD scores were 6 and 17, respectively.

Zinc level distribution was normal using the Kolmogorov-Smirnov test. The mean of zinc level (71.32 ± 25.01) was significantly lower than normal population (P value = 0.0001, CI95% = 65.5–76.5) (Fig. 1) (Table 3).

Fig. 1
figure 1

Zinc level among children with liver cirrhosis

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Table 3 Magnesium, zinc, and vitamin D level among children with liver cirrhosis
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The minimum and maximum levels of zinc were 25.2 mcg/dl and 147.1 mcg/dl, respectively. Zinc level was lower than the normal range among 23% of children with liver cirrhosis. The mean level of zinc was 71.32 ± 25.01 mcg/dl. The median level of zinc was 69.7mcg/dl (Table 3).

There is a significant inverse correlation between zinc level and PELD score (Pearson correlation = − 0.314, P = 0.007)

The distribution of magnesium levels was abnormal (Fig. 2). There was a significant difference between children with liver cirrhosis and the normal population in terms of the level of magnesium using the chi-square test (χ2 = 32.67, P = 0.0001) (Table 3). Magnesium level according to etiology of cirrhosis is shown in Fig. 3.

Fig. 2
figure 2

Magnesium level among children with liver cirrhosis

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Fig. 3
figure 3

Magnesium level according to the etiology of liver cirrhosis

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There was a significant difference between the level of vitamin D among children with liver cirrhosis and normal level (chi-square = 4, P = 0.0455) (Table 2). There was no significant correlation between vitamin D level and PELD score (Pearson correlation = − 0.205, P = 0.058). Vitamin D, zinc, and magnesium levels according to underlying disease are shown in Table 4. As seen in Table 4, the highest mean level of vitamin D was seen among PFIC patients. Vitamin D levels according to etiology of liver disease are shown in Fig. 4.

Table 4 Magnesium, zinc, and vitamin D among children according to the underlying disease
Full size table
Fig. 4
figure 4

Vitamin D level among different etiologies of cirrhosis

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Discussion

The liver is the main organ for the metabolism of nutrients.

Our study showed that 53% of the children with liver cirrhosis had vitamin D deficiency. In the study by Jamil et al., vitamin D deficiency was found in 88% of patients with liver disease [10]. In the study by Paternostro et al., vitamin D deficiency was seen in 40% of the patients with liver cirrhosis [11]. In the study by Konstantakis et al., vitamin D deficiency had a great relationship with liver function [12]. In the study by Buonomo et al., vitamin D deficiency harmed the survival of the patients with liver cirrhosis [13]. We did not find a significant correlation between vitamin D level and PELD score. A significant correlation between vitamin 25-OH vitamin D3 level and poor outcome according to MELD and Child-Pugh score was found by Kim et al. [14].

Kumar et al. found that 80% of patients with liver cirrhosis had some degree of vitamin D deficiency [15]. In another study, 87% of patients with chronic liver disease showed insufficient or deficient vitamin D [16]. Vitamin D deficiency was shown in most studies. In the study by Jazayeri et al., the prevalence of vitamin D deficiency in Iranian boys and girls were 35% and 61%, respectively [17]. The prevalence of vitamin D insufficiency in Iranian children and adolescents was 31% [17]. As a result, the frequency of vitamin D deficiency was higher than healthy apparent Iranian children.

In the current study, magnesium level was higher than the normal level among 99% of children with liver cirrhosis. But in the study by Kohen et al., magnesium deficiency was frequent among patients with liver cirrhosis [18]. In the study by Wang et al., magnesium deficiency was reported in patients with liver cirrhosis [19]. Significant changes in magnesium levels between patients with liver disease and the healthy population were not found in the study by Rahelic et al. [20]. In another study by Göksu and Ozsoylu, magnesium was decreased among children with liver cirrhosis [21]. Other studies had similar findings in terms of magnesium deficiency in liver cirrhosis [22]. Among Iranian healthy children, the prevalence of hypomagnesemia was 5.9% [23]. Magnesium deficiency was expected in children with liver cirrhosis. But this difference has happened. Diet may have played an important role for example rice which was an important source of Iranian food [24]. Another study is recommended to find the cause of hypermagnesemia among children with liver cirrhosis.

Zinc deficiency was seen in 23% of children in our study. Zinc deficiency is a major health problem especially in developing countries [25]. Zinc deficiency was very frequent among developing countries rated between 46% in the Middle East and 79% in South Asia [26, 27]. Even in Western European countries, the prevalence of zinc deficiency was high [28]. Zinc deficiency may lead to hepatic encephalopathy [29, 30]. Zinc deficiency was reported as a frequent finding among cirrhotic patients [31]. In the study by Katayama et al., zinc deficiency was common among patients with liver cirrhosis. In the study by Sengupta et al., zinc deficiency was highly prevalent among children with liver cirrhosis [32]. Sengupta and colleagues recommended screening for zinc deficiency [32]. In the study by Azemati et al. among 3500 Iranian healthy children aged 7–15 years, the prevalence of zinc deficiency was 5% [33]. In the study by Dehghani et al., the prevalence of zinc deficiency was 7.9% [27]. In the study by Dehghani et al. on 902 children without liver disease [27], zinc level was 122.3 ± 55 mcg/dl. The result of our study was lower than Dehghani et al.’s study and show zinc level was lower in children with cirrhosis than in children without liver disease. Although due to the high frequency of zinc deficiency in the world [26], multiple factors play a role in zinc deficiency in children with liver cirrhosis. As a result, the prevalence of zinc deficiency among children with liver cirrhosis was higher than that among Iranian healthy apparent children [27]. According to the high prevalence of zinc deficiency in the world, cirrhosis may play as one factor in zinc deficiency.

Conclusion

Zinc and vitamin D deficiency was prevalent among children with liver cirrhosis. The serum magnesium level was higher in cirrhotic children compared to the standard level. Further studies are recommended to clarify changes in magnesium and zinc in children with liver cirrhosis with more samples.

Limitation

This study was a single-center study. In this study, we used standard values as the reference instead of healthy control. We used the standard level of zinc and magnesium for comparison. Due to the low sample size of some etiologies, some analysis was not possible. Dietic history was not included in the current research.

Abbreviations

AIH:

Autoimmune hepatitis

CHF:

Congenital hepatic fibrosis

INH:

Idiopathic neonatal hepatitis

PELD Score:

Pediatric Endstage Liver Disease Score

PFIC:

Progressive familial intrahepatic cholestasis 

PSC:

Primary sclerosing cholangitis

References

  1. Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, Caregaro L (2001) Nutrition and survival in patients with liver cirrhosis. Nutrition (Burbank, Los Angeles County, Calif) 17(6):445–450

    CAS  Article  Google Scholar 

  2. Tajika M, Kato M, Mohri H, Miwa Y, Kato T, Ohnishi H, Moriwaki H (2002) Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition (Burbank, Los Angeles County, Calif) 18(3):229–234

    CAS  Article  Google Scholar 

  3. Dehghani SM, Imanieh MH, Haghighat M, Malekpour A, Falizkar Z (2013) Etiology and complications of liver cirrhosis in children: report of a single center from southern Iran. Middle East J Digest Dis 5(1):41–46

    Google Scholar 

  4. Stamoulis I, Kouraklis G, Theocharis S (2007) Zinc and the liver: an active interaction. Dig Dis Sci 52(7):1595–1612

    CAS  Article  Google Scholar 

  5. Capocaccia L, Merli M, Piat C, Servi R, Zullo A, Riggio O (1991) Zinc and other trace elements in liver cirrhosis. Italian J Gastroenterol 23(6):386–391

    CAS  Google Scholar 

  6. Shen YC, Chang YH, Fang CJ, Lin YS (2019) Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis. Nutr J 18(1):34

    Article  Google Scholar 

  7. Alsahhar JS, Rahimi RS (2019) Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy. Curr Opin Gastroenterol 35(3):145–154

    CAS  Article  Google Scholar 

  8. Oralewska B, Zawadzki J, Jankowska I, Popinska K, Socha J (1996) Disorders of magnesium homeostasis in the course of liver disease in children. Magnes Res 9(2):125–128

    CAS  PubMed  Google Scholar 

  9. Ramadan HK, Makhlouf NA, Mahmoud AA, Abd Elrhman M, El-Masry MA (2019) Role of vitamin D deficiency as a risk factor for infections in cirrhotic patients. Clin Res Hepatol Gastroenterol 43(1):51–57

    CAS  Article  Google Scholar 

  10. Jamil Z, Arif S, Khan A, Durrani AA, Yaqoob N (2018) Vitamin D deficiency and its relationship with child-Pugh class in patients with chronic liver disease. J Clin Transl Hepatol 6(2):135–140

    Article  Google Scholar 

  11. Paternostro R, Wagner D, Reiberger T, Mandorfer M, Schwarzer R, Ferlitsch M, Trauner M, Peck-Radosavljevic M, Ferlitsch A (2017) Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr 129(1-2):8–15

    CAS  Article  Google Scholar 

  12. Konstantakis C, Tselekouni P, Kalafateli M, Triantos C (2016) Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol 29(3):297–306

    PubMed  PubMed Central  Google Scholar 

  13. Buonomo AR, Scotto R, Zappulo E, Nerilli M, Pinchera B, Perruolo G, Formisano P, Nappa S, Gentile I (2019) Severe vitamin D deficiency increases mortality among patients with liver cirrhosis regardless of the presence of HCC. In vivo (Athens, Greece) 33(1):177–182

    CAS  Google Scholar 

  14. Kim TH, Yun SG, Choi J, Goh HG, Lee HA, Yim SY, Choi SJ, Lee YS, Yoon EL, Jung YK et al (2020) Differential impact of serum 25-hydroxyvitamin D3 levels on the prognosis of patients with liver cirrhosis according to MELD and child-Pugh scores. J Korean Med Sci 35(19):e129

    CAS  Article  Google Scholar 

  15. Kumar R, Kumar P, Saxena KN, Mishra M, Mishra VK, Kumari A, Dwivedi M, Misra SP (2017) Vitamin D status in patients with cirrhosis of the liver and their relatives-a case control study from North India. Indian J Gastroenterol 36(1):50–55

    Article  Google Scholar 

  16. Fernandez Fernandez N, Linares Torres P, Joao Matias D, Jorquera Plaza F, Olcoz Goni JL (2016) Vitamin D deficiency in chronic liver disease, clinical-epidemiological analysis and report after vitamin d supplementation. Gastroenterol Hepatol 39(5):305–310

    Article  Google Scholar 

  17. Jazayeri M, Moradi Y, Rasti A, Nakhjavani M, Kamali M, Baradaran HR (2018) Prevalence of vitamin D deficiency in healthy Iranian children: a systematic review and meta-analysis. Med J Islam Repub Iran 32:83

    Article  Google Scholar 

  18. Cohen-Hagai K, Feldman D, Turani-Feldman T, Hadary R, Lotan S, Kitay-Cohen Y (2018) Magnesium deficiency and minimal hepatic encephalopathy among patients with compensated liver cirrhosis. Israel Med Assoc J: IMAJ 20(9):533–538

    Google Scholar 

  19. Wang FJ, Cao J, Ma LP, Jin ZX (2004) Study on cellular and serum concentration of calcium and magnesium in peripheral blood cells of cirrhosis. Zhonghua Gan Zang Bing Za Zhi 12(3):144-7.

  20. Rahelic D, Kujundzic M, Romic Z, Brkic K, Petrovecki M (2006) Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis. Collegium Antropologicum 30(3):523–528

    CAS  PubMed  Google Scholar 

  21. Göksu N, Ozsoylu S (1986) Hepatic and serum levels of zinc, copper, and magnesium in childhood cirrhosis. J Pediatr Gastroenterol Nutr 5(3):459–462

    Article  Google Scholar 

  22. Peng X, Xiang R, Li X, Tian H, Li C, Peng Z, Xiang M (2021) Magnesium deficiency in liver cirrhosis: a retrospective study. Scand J Gastroenterol 56(4):463–468

    CAS  Article  Google Scholar 

  23. Ghasemi A, Syedmoradi L, Zahediasl S, Azizi F (2010) Pediatric reference values for serum magnesium levels in Iranian subjects. Scand J Clin Lab Invest 70(6):415–420

    CAS  Article  Google Scholar 

  24. Shariatifar N, Rezaei M, Alizadeh Sani M, Alimohammadi M, Arabameri M (2020) Assessment of rice marketed in Iran with emphasis on toxic and essential elements; effect of different cooking methods. Biol Trace Elem Res 198(2):721–731

    CAS  Article  Google Scholar 

  25. Maxfield L, Shukla S, Crane JS (2022) Zinc deficiency. In: StatPearls. StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC, Treasure Island

    Google Scholar 

  26. Maret W, Sandstead HH (2006) Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 20(1):3–18

    CAS  Article  Google Scholar 

  27. Dehghani SM, Katibeh P, Haghighat M, Moravej H, Asadi S (2011) Prevalence of zinc deficiency in 3-18 years old children in shiraz-Iran. Iran Red Crescent Med J 13(1):4–8

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Vreugdenhil M, Akkermans MD, van der Merwe LF, van Elburg RM, van Goudoever JB, Brus F (2021) Prevalence of zinc deficiency in healthy 1-3-year-old children from three Western European countries. Nutrients 13(11):3713. https://doi.org/10.3390/nu13113713.

  29. Himoto T, Masaki T (2018) Associations between zinc deficiency and metabolic abnormalities in patients with chronic liver disease. Nutrients 10(1):88

  30. McClain CJ, Antonow DR, Cohen DA, Shedlofsky SI (1986) Zinc metabolism in alcoholic liver disease. Alcohol Clin Exp Res 10(6):582–589

    CAS  Article  Google Scholar 

  31. Katayama K, Kawaguchi T, Shiraishi K, Ito T, Suzuki K, Koreeda C, Ohtake T, Iwasa M, Tokumoto Y, Endo R et al (2018) The prevalence and implication of zinc deficiency in patients with chronic liver disease. J Clin Med Res 10(5):437–444

    CAS  Article  Google Scholar 

  32. Sengupta S, Wroblewski K, Aronsohn A, Reau N, Reddy KG, Jensen D, Te H (2015) Screening for zinc deficiency in patients with cirrhosis: when should we start? Dig Dis Sci 60(10):3130–3135

    CAS  Article  Google Scholar 

  33. Azemati B, Khoramdad M, Qorbani M, Rastad H, Shafiee G, Heshmat R, Kelishadi R (2020) Percentile values of serum zinc concentration and prevalence of its deficiency in Iranian children and adolescents: the CASPIAN-V study. J Pediatr Endocrinol Metab 33(4):525-531

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Authors and Affiliations

  1. Gastroenterohepatology Research Center, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Mohsen Dehghani

  2. Dept. of Pediatric Endocrinology and Metabolism, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Anis Amirhakimi

  3. Dept. of Pediatrics, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Parisa Baligh

  4. Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Clinical Sciences Research Institute, Ahvaz, Iran

    Hazhir Javaherizadeh

Authors
  1. Seyed Mohsen Dehghani
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  2. Anis Amirhakimi
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  3. Parisa Baligh
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  4. Hazhir Javaherizadeh
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Contributions

SMD had the main idea and wrote the manuscript and also has a role in the revision of the manuscript. AA has arole in writing the manuscript and revision of the manuscript. PB has a role in data collection, writing a researchproposal, and data analysis. HJ performed the literature review and has a role in writing manuscript, revision ofmanuscript, and data analysis. All the authors read and approved the manuscript.

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Correspondence to Hazhir Javaherizadeh.

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Dehghani, S.M., Amirhakimi, A., Baligh, P. et al. Evaluation of micronutrients among pediatric liver cirrhosis in Shiraz, Iran. Egypt Liver Journal 12, 18 (2022). https://doi.org/10.1186/s43066-022-00182-3

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Keywords

  • Cirrhosis
  • Liver
  • Magnesium
  • Zinc