Trace elements play a major role as both oxidants and antioxidants, promoting and protecting from tissue damage. The liver plays a pivotal role in the metabolism of trace elements and consequently their bioavailability. Therefore, we aimed to measure serum levels of essential trace elements in children with chronic liver diseases (CLDs) and to study their correlation with liver function tests.

1. Serum copper, iron and zinc in children with chronic liver disease
Noha L. Ibrahim*, Ahmad M. Sira**
* Molecular Diagnostics Departments, Genetic Engineering and Biotechnology Research Institute (GEBRI), Menofiya
University, Egypt.
** Pediatrics Hepatology Department, National Liver Institute, Menofiya University, Egypt.
AIM OF THE WORK
AIM OF THE WORK
Measurement of serum level of essential trace elements
in children with CLD regardless the etiology and
correlate these serum levels with biochemical measures
of liver damage and other liver function tests.
CONCLUSION
In conclusion, our finding of significantly higher serum Fe,
Cu, and ferritin in children with CLD than healthy controls
and its positive correlation with biochemical parameters of
liver damage and the significantly lower serum Zn in CLD
than that in healthy controls and its negative correlation
with biochemical parameters of liver damage encourage
the inclusion of these trace elements as biomarkers for
monitoring the severity of liver damage during routine
assessment of children with CLD. Finally, we recommend
caution to avoid excess Fe and Cu intake in such patients,
while zinc supplementation is encouraged regardless the
etiology of CLD.
Study population
This study included 50 children with CLD (27 males and 23 females, with mean of age 5.86 ± 4.76 years).
They were taken from the attendants of the outpatient and inpatient clinic of pediatric hepatology
department, National Liver Institute, Menofiya University from October 2010 to February 2012. Another
group of 50 age and sex matched healthy children were enrolled as a control group (25 males and 25
females, with mean of age 6.62 ± 3.54 years). None of the participants had received mineral supplements
before blood sampling.
Etiological diagnosis
After full history taking, thorough clinical examination, the etiological diagnoses of the CLD group were
autoimmune hepatitis (n=7), chronic hepatitis C (n=5), Alagille syndrome (n=5), cytomegalovirus
hepatitis (n=4), progressive familial intrahepatic cholestasis (n=3), neglected biliary atresia (n=3), chronic
hepatitis B (n=2), glycogen storage disease (n=2), Crigler Najjar syndrome (n=2), congenital hepatic
fibrosis (n=2), Niemann Pick disease (n=2), inspissated bile syndrome (n=2), toxoplasma hepatitis (n=2),
Caroli syndrome (n=2), portal vein thrombosis (n=2), Wilson disease (n=1), Dubin-Johnson syndrome
(n=1), Budd Chiari syndrome (n=1), alpha1 antitrypsin deficiency (n=1) and cystic fibrosis (n=1).
Laboratory investigations
Liver function tests (Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase
(ALP), gamma glutamyle transpeptidase (GGT), total bilirubin, direct bilirubin, total proteins and serum
albumin) were measured using Automated Beckman Coulter. Serum Zn, Cu, and Fe were measured by
colorimetric assay at a wave length of 560 nm (for Zn), 580 nm (for Cu), 546 nm (for Fe) using
Biosystems BTS-310 photometer chemistry analyzer. TIBC was measured based on ferrozine method by
Spectrum Diagnostic for the in-vitro quantitative, diagnostic determination of TIBC in human serum,
serum ferritin was measured by ELISA (enzyme-linked immunosorbent assay) using the UBI
MAGIWEL™ FERRITIN QUANTITATIVE device and serum transferrin saturation (TS) was calculated
by dividing serum Fe by TIBC.
Statistical analysis
Descriptive results were expressed as mean ± SD (standard deviation) or number and percentage. For
qualitative data, significance was tested using Chi square test. For quantitative data, significance between
groups was tested using the Student's t- test for parametric data and by Mann-Whitney test for nonparametric data. Correlation was tested using Pearson’s correlation. Results were considered significant
when P-value was less than 0.05. Statistical analysis was carried out using SPSS (statistical package for
social science) program version 13 (SPSS Inc., Chicago, Illinois, USA) on an IBM compatible computer.
RESULTS
Box-and-whiskers plot for serum trace elements in the studied groups. The top and bottom of each box are the 75th and 25th centiles.
The line through the box is the median and the error bars are the maximum and minimum. The horizontal bar represents the
significance between the designated groups. Serum Cu, Fe, ferritin, and TS were significantly higher in the CLD than that in the control
group; while Zn and TIBC were significantly lower in the CLD than that in the control group (P < 0.01)
6.62
250
50
6
200
40
5
46
6
5
4
3
2
50
50
Control
20
2
0
50
1
Femal
Male
CLD Control
Figure 1: Comparison between the
CLD and control group regarding
age.
100
3
0
CLD
150
4
30
10
1
0
54
300
8
7
5.86
7
Percentage (%)
Chronic liver disease (CLD) in children constitutes a
major health burden on both parents and the diseased
child. They may be caused by infectious, autoimmune,
metabolic, vascular, drugs and toxins or unidentified
etiologies. Many of these CLDs progress towards
cirrhosis and eventually liver failure. In spite some of
these disease categories are subjected to specific
treatment with good prognosis, much are not, specially
when there is no an identifiable etiology.
 Liver regulates the metabolic pathways and transport
of trace elements, and consequently their bioavailability,
tissue distribution and eventual toxicity. The liver also
has a role in the excretion of trace elements through bile
formation. Growing evidence indicates that many trace
elements play important roles in a number of biological
processes through activation or inhibition of enzymatic
reactions, competing with other elements and
metalloproteins for binding sites, and affecting the
permeability of cell membranes. Moreover, some trace
elements such as zinc (Zn), iron (Fe), and copper (Cu)
exert important protective or enhancing effects on the
progression of some diseases .
Zinc is involved in stabilizing the cell membrane and
prevents oxidative destruction caused by free radicals.
The antioxidant actions of Zn include the induction of
metallothionein (Zn-binding protein, formed by the
liver), which is a potent scavenger of toxic metals and
hydroxyl radical ). Fe and Cu ions catalyze the
production of hydroxyl radical from hydrogen peroxide
(H2O2). Zn is known to compete with both Fe and Cu
for binding to cell membrane, thus decreasing the
production of hydroxyl radical. Thus, it is clear that Zn
has multiple roles as an antioxidant and is therefore, an
excellent candidate for clinical chemoprevention trials in
humans.
PATIENTS & METHODS
PATIENTS & METHODS
Age in years
INTRODUCTION
0
ALT
Total Bil
D. Bil
Total prot
AST
ALP
GGT
Alb
CLD Control
Figure 3: Comparison of total
Figure
2:
Comparison
protein, albumin, total and
between the CLD and control
direct bilirubin between CLD
group regarding sex.
CLD
Control
Figure 4: Comparison of
ALT,AST,ALP and GGT
between CLD group and
control group.