Mykhailiuk K. Improvement of diagnosis and evaluation of clinical course of autoimmune hepatitis in children.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0419U004515

Applicant for

Specialization

  • 14.01.10 - Педіатрія

22-10-2019

Specialized Academic Board

Д 26.553.01

SI «Institute of Pediatrics, Obstetrics and Gynecology named academician O. M. Lukyanovaya NAMS of Ukraine»

Essay

Dissertation is devoted to the problem of increasing of the diagnostic efficiency of the autoimmune hepatitis progressive course in children by studying the influence of vitamin D supply on the disease course, variants of the VDR gene polymorphism and evaluation of the results of shear wave elastography in the diagnosis of liver fibrosis in these patients. It is known that AH is predominantly spread among girls of prepubertal and pubertal age and this quantity makes 68,0% against 32,0% among boys (р < 0,005). Autoimmune pathology was high enough in the families of patients with AH reaching 30% among first line relatives. AH I type predominates in children and makes 80,0%; AH II type was detected in one patient and seronegative type of AH was found in 12%. Clinical manifestations of the diseases were found nonspecific and similar to the same in acute hepatitis. Histological activity (Knodell) degree and inflammation biochemical activity in the liver, according to our data, are not identical but significantly complement each other what can be proved by the fact of 5 times transaminases level increase in 19,0% of children with high histological activity. According to the results of liver’s biopsy morphology it was detected that prevailing majority of children with AH had marked fibrosis and initial signs of cirrhosis (F3-4 METAVIR) - 67,0%. Morphological signs of cirrhosis were found in 22,0% of children. Moderate and high histological activity was diagnosed in 62,0% patients. 68,0% of children with AH have vitamin D deficiency, which doesn’t depend on the season and region of residence. Histological activity and stage of fibrosis affect the level of 25(OH)D in serum. In patients with IHA <9 points, the proportion of children with vitamin D deficiency was 25,0%, and in patients with IНA> 9 points - 75,0%.Analysis of vitamin D availability in patients with different stages of fibrosis according to morphological study showed that in children with stage F2 METAVIR the proportion of children with vitamin D deficiency was 67,0%, with fibrosis stage F3- 75,0% and in patients with liver cirrhosis –90,0% (р>0,05). Vitamin D deficiency in children with autoimmune hepatitis is associated with genetic peculiarities of patients such as GA genotype VDR gene BsmI polymorphic variant and AC/TC/GA genotypes combinations of VDR receptor’s gene ApaI, TagI and BsmI variants(p<0,05). CC genotype of VDR receptor’s gene TagI polymorphic type and combination of AA/CC/AA genotypes ofApaI, TagI, BsmI gene’s polymorphic variants were associated with remarkable fibrosis F3and F4 METAVIR (p<0,05). Immunosuppressive therapy has been shown to lead to curative pathomorphosis of AH. In 66,0% of patients fibrosis stage detected in histological investigation coincided with liver elastography results. The use of shear wave ultrasound elastography for fibrosis stage detection in children with AH during period of thriving clinical manifestations is not reasonable as far as hepatitis activity influences the indexes of liver’s parenchyma density. A method of determining the stage of liver fibrosis by a non-invasive method for treatment without taking into account the activity of the inflammatory process in the liver using the developed formula is proposed and the optimal timing of this study. Diagnostic predictors of the progressive course of AH in children have been as well established.

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