Boiko V. Pаtogenetic value of cytokine regulatory network and the genotype of the virus in the formation of clinical course in patients with viral hepatitis A

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0420U100919

Applicant for

Specialization

  • 14.01.13 - Інфекційні хвороби

30-06-2020

Specialized Academic Board

Д 64.609.05

The Kharkiv Medical Academy of Postgraduate Education, Ministry of Health of Ukraine

Essay

The aim of the study is to improve the diagnosis of hepatitis A by determining prognostic criteria for the development of a protracted course of the disease based on the study of clinical and laboratory features and cytokine reactivity of patients, depending on the genotype of the virus. Integrated clinical diagnostic laboratory tests were held in order to examine 141 patients at the age of 18-60 years with HA. For the first time in Ukraine was held HAV genotyping. It was also determined two genotypes circulation IA and IIIA. But however only genotype IA was identified in some regions of Ukraine in another ones both IA and IIIA genotypes were registered. The HAV genotype role in disease severity formation was defined: IIIA HAV genotype is one of the factors leading to moderate form of disease formation as well as to unfavorable course of disease. For the first time peculiarities of HA with different virus genotypes were revealed. HA peculiarities resulted from IIIA HAV include often registration of fever during jaundice, headache, nausea, bad mouth smell, enlarged spleen, muffled heart sounds, itchy skin (p<0,05), higher content of ALT and alkaline phosphatase (p<0,05), more expressive changes of liver ultrasound (p<0,05). General bilirubin level is higher in moderateA H of the IIIA genotype (p<0.05). For the first time it was found out that disease severity formation as well as recovery processes in HA patients with different virus genotypes take place against the background of different reactivity of cytokines system. It was detemined that course of HA caused by IIIA virus genotype is accompanied by expressive reaction of pro-inflammatory cytokines (p<0,01) at the beginning of the disease with insignificant fluctuations of anti-inflammatory IL levels (p>0,05); and in patients with VHA of IA genotype significant fluctuations both – pro-inflammatory and anti-inflammatory blood IL (р<0,01). First-rank position according to the importance degree in HA patients of IA genotype occupies IL-2 and as for IIIA genotype patients – there goes to TNFα. Hypoactive cytokine response during convalescence in patients with genotype IIIA was revealed. It was firstly uncovered that the severity of HA at the beginning is characterized by more frequent registration of the following symptoms: fever, nausea, bad mouth smell, headache, joint pain, heaviness in the right hypochondrium, enlarged spleen, itchy skin, dyspeptic syndrome, intense urine colour (p<0,05), higher indexes of bilirubin, higher indexes of cytolytic enzymes levels, higher indexes of the thymol turbidity test, higher indexes of alkaline phosphatase and γ-glutamyltransferase against the background of decreasing content of protein (p<0,05), increased vascular pattern of the liver according to ultrasound, signs of splenitis and mesadenitis (p<0,05),expressive reaction of both pro- and anti-inflammatory IL in the blood(p<0,05). The feasibility of using clinical and laboratory predictors (a diagnostic algorithm has been developed) for the prolonged course of HA, which allows one to predict its development with high reliability (≥95 %).

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