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"Child`s Health" 3 (54) 2014

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The comparative evaluation of the state of hepatobiliary system in children who live in the ecologically unfavourable districts polluted with different types of xenobiotics

Authors: M. Luchak, O. Hnateiko, N. Kech, H. Chaykovska - Institute of Hereditary Pathology of National Academy of Medical Sciences of Ukraine, Lviv.

Categories: Pediatrics/Neonatology

Sections: Clinical researches

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Introduction. Over the past decade epidemiologic studies worldwide have measured increases in mortality and morbidity associated with pollution. Environmental pollution is a significant risk factor for many environmentally triggered diseases. The impact of man-made environmental pollutants on humans leads to environmental maladaptation syndrome and can modulate the clinical course of diseases. The term "environmentally triggered disease" means the pathological processes caused by influence of low doses and low-intensity aggressive environmental factors that generally act without dose-effects relationships. Despite the fact that the environmental toxicants  are at doses far below threshold, but they can appear as susceptibility factors, modifying and enhancing factors and choose the sphere of their action the most susceptible sections of the population, on the one hand, and the most sensitive organs, on the other hand.

Children are the most sensitive to xenobiotics due to the immaturity of biotransformation, elimination, and other physiologic systems as a result it increases risk for various diseases. One of the most sensitive system to environmental toxicants is hepatobiliary system, which on the one hand, is responsible for maintenance of many homeostatic and physiological functions, on the other hand, is involved in the biotransformation of xenobiotics, providing hydrolytic and conjugation reactions of toxic compounds and biliary excretion of high molecular weight and hydrophobic xenobiotics. Therefore, the problem of preclinical diagnosis of environmentally triggered hepatobiliary disease and monitoring of high-risk group of children is actual and advanced.

We studied environmentally triggered hepatobiliary disease in children from the ecologically unfavourable districts (Rogatyn and Bohorodchany districts of Ivano-Frankivsk region). Rogatyn district was accepted as polluted region by mainly inhaled xenobiotics, whereas children were exposed to ingestive toxins in Bohorodchany district.

In view of the foregoing, the purpose of this study was to optimize early diagnosis of environmentally triggered hepatobiliary disease in children who had been living in polluted region on the basis of testing for markers of early liver damage.

Materials and methods. We enrolled 63 children under different ecological conditions. The first group included 31 children who have been living in Rogatyn district which was officially accepted as the area of chemical contamination mainly by inhaled xenobiotics (I-RS). The second group included 32 children from Bohorodchany district. There was chemical contamination of the ingestive toxins (II-GIT). In addition, 34 children who have been living in environmentally safe district of Ivano-Frankivsk region were examined – III-ESD (control group).

General clinical examination, diagnostic ultrasonography of internal organs and laboratory tests were conducted on every patient.Biochemical blood analysis was done by routine biochemical methods. Sorbitol dehydrogenase activity was determined by the method of Pirkov based on conversion of D-fructose to sorbitol with simultaneous oxidation of NADH.

Results and discussion. All the children were in satisfactory condition. The analysis of ultrasonography in children from polluted regions showed the high incidence of thyroid, gallbladder and renal pathologies (I-RS – 74 %, 19 %, 26 %; II-GIT – 37 %, 21 %, 61 %, respectively). The frequencies were significantly higher compared with the results of III-ESD group where thyroid pathology diagnosed in 31 % of children, gallbladder pathology - only in 3 %, kidney - 4 % of children (p < 0.01).It should be noted that ultrasonography signs of hepatomegaly were found in 42 % children of II-GIT who were exposed to ingestive toxins. It was approximately fourteen times more often than in children in the III-ESD (3 %) and 1.6 times more frequently than in children living in the polluted region by inhaled xenobiotics (I-RS – 26 %).

The high frequency of ultrasonographic markers of liver, gallbladder, thyroid and renal diseases provided the opportunity for suspecting these pathologies as dominant in the clinical manifestations of environmentally triggered disease in examined children.

Liver function tests were conducted to identify liver damage in children from districts with different types of the environmental pollution. The average concentrations of serum alanine (ALT) and aspartate transaminases (AST) in I-RS were not differ from that in III-ESD (ALT - 0,12 ± 0,01mmol/l, AST - 0,11 ± 0,01mmol/l vs. 0,12mmol/l, 0,14mmol/l, respectively), whereas the average level of ALT in II-GIT was 0,20 ± 0,02mmol/l and was significantly higher in comparison with the results in III-ESD (p < 0,01). Among the examined children in II-GIT there were 11 patients (34,4%) who had slight increase of serum ALT levels. Consequently, children who were exposed to ingestive toxins had diagnosed mild hepatocellular damagethat was not observed in I-RS and III-ESD groups.

Whereas sorbitol dehydrogenase activity was increased significantly in the both groups of children from polluted regions compared to control group (I-RS - 0,009±0,003 mkmol/ml/min., II-GIT - 0,027±0,003mkmol/ml/min vs. III-ESD - 0,003 ± 0,001mkmol/ml/min, p < 0,01). In 29.0 % patients of I-RS group who were exposed to inhaled xenobiotics and in 75.0 % children of II-GIT group who were exposed to ingestive toxins the mean sorbitol dehydrogenase activities were higher than that in III-ESD group.

The average activities of alkaline phosphatase in both groups from polluted regions were significantly higher compared to that in III group (I-RS - 8 681,8 ± 482,5nmol/s.l., II-GIT - 6286 ± 528nmol/s.l., vs. III-ESD - 4135,9 ± 432,9nmol/s.l., p < 0,01). The mean concentration of gamma-glutamyltransferase (GGT) in II-GIT group who were exposed to ingestive xenobiotics was statistically different from that in the III group (0,58 ± 0,07mKat/L. vs. 0,27 ± 0,05mKat/L, p < 0,01). The 62 % of patients in II-GIT group had mild increase of serum GGT levels. Thus, the mean GGT activity in children of I-RS who were exposed to inhaled toxins was not significantly higher than the results of III-ESD group, but cohort of patients with hyperfermentemia was significantly different to III-ESD group (48 vs. 3 %, p < 0,01). These data suggested that a possible early manifestation of liver dysfunction in children from polluted regions was the beginning of cholestasis, the early manifestation of which was the rise of the activities of GGT and alkaline phosphatase in serum.

Conclusions.

Environmentally triggered disease in children was a multi-system disorder, the leading of which were hepatobiliary, renal and thyroid pathologies.

Our results found that early sign of liver dysfunction was the beginning of cholestasis, the early biochemical markers of which were gamma-glutamyltransferase and alkaline phosphatase in children from polluted regions regardless of the route of exposure.

It was observed the elevation of the activity of cholestatic and hepatocellular enzymes in children who were exposed to ingestive toxins whereas there were only early laboratory signs of cholestasis in exposed patients to inhaled xenobiotics. Consequently, environmentally triggered hepatobiliary disease was more severe disorder in children who were exposed to ingestive toxins than in those who were exposed to inhaled xenobiotics.


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