SUBCLINICAL INFLAMMATION IN NON/ALCOHOLIC FATTY LIVER DISEASE AT THE REMOTE PERIOD AFTER THE CHORNOBYL ACCIDENT. / SUBKLINIChNE ZAPALENNIa PRY NEALKOGOL'NII ZhYROVII KhVOROBI PEChINKY U VIDDALENOMU PERIODI PISLIa ChORNOBYL'S'KOÏ AVARIÏ.

OBJECTIVE: to evaluate the parameters of inflammatory reaction and oxidative stress in patients with non-alcoholicfatty liver disease (NAFLD) in the remote period after the influence of the Chornobyl accident factors. MATERIALS AND METHODS: Eighty two patients with NAFLD who had been exposed to ionizing radiation as a result ofthe Chornobyl accident and have concomitant cardiovascular pathology were examined. Hematological parametersand the level of highly sensitive C-reactive protein (hsCRP) were determined, and the content of products of oxida-tive modification of lipids and proteins was evaluated. RESULTS: Activation of the processes of oxidative modification of lipids and proteins was observed in most patientswith NAFLD. According to the level of hsCRP, the presence of subclinical inflammation and the risk of developingcomplicated cardiovascular pathology was found in 58 % of patients with NAFLD. The neutrophil / lymphocyte ratiocorrelates positively with hsCRP and can be used as an available routine clinical marker for selection among patientswith NAFLD persons with increased risk of cardiovascular complications. CONCLUSIONS: HsCRP, oxidative modification products of lipids and proteins, ESR, and leukograms should be used toassess the degree of systemic inflammation in people affected by the Chornobyl accident, suffering NAFLD with con-comitant cardiovascular disease.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

THE EFFECT OF APPLICATION OF ANTIOXIDANT THERAPY IN THE TREATMENT OF NON-ALKOHOLIC STEATOHEPATATIS IN CHORNOBYL NPP ACCIDENT SUFFERERS IN THE REMOTE PERIOD AFTER IRRADIATION. / ZASTOSUVANNIa ANTYOKSYDANTNOÏ TERAPIÏ V LIKUVANNI NEALKOGOL'NOGO STEATOGEPATYTU U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES U VIDDALENYI PERIOD PISLIa OPROMINENNIa.

OBJECTIVE: to determine the effectiveness of combined treatment with hepatoprotectors and antioxidant a complexpreparation of vitamins A and E (I) in patients with non-alcoholic steatohepatitis (NASH) who suffered from theChornobyl NPP accident based on the results of evaluation of metabolic changes. MATERIALS AND METHODS: The state of the hepatobiliary system of 72 patients with NASH suffered as a result of theChornobyl accident was studied based on the results of the biochemical analysis of blood, indicators characterizingthe processes of oxidative modification of macromolecules and the state of the antioxidant system (AOS), as well asstructural changes in the liver according to ultrasound investigations in the course of the examination before andafter treatment. RESULTS: The treatment of NASH with hepatoprotectors and antioxidant I in the sufferers of the Chornobyl accidentincreased the level of antioxidant defense products (catalase and superoxide dismutase) with the normalization ofthe integral index of the AOS, and a significant decrease in the number of patients with reduced AOS status (from42.6% to 24, 2%, p <0.05), positive dynamics of biochemical parameters of blood with decreasing frequency ofdetection of cholestasis syndrome, hypercholesterolemia and hyperglycemia were established as well as the positivedynamics of structural changes in the liver according to ultrasound data. CONCLUSION: Combined therapy of NASH with hepatoprotectors and antioxidant I in patients who suffered from theChornobyl NPP accident contributes to the restoration of the prooxidant-antioxidant balance, decreases cholestasis,hypercholesterolemia and hyperglycemia, and promotes positive dynamics of structural changes in the liver.

Comparative characteristics of hepatoprotectors used for the treatment of non alcoholic steatohepatitis associated with herpesvirus infection in sufferers of the Chornobyl accident. / PORIVNIaL'NA KhARAKTERYSTYKA GEPATOPROTEKTORIV, ZASTOSOVANYKh DLIa LIKUVANNIa NEALKOGOL'NOGO STEATOGEPATYTU, ASOTsIY̆OVANOGO Z GERPESVIRUSNOIu INFEKTsIIeIu, U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

Objective of the study was to determine the effectiveness of various groups of hepatoprotectors in the treatment of patients with nonalcoholic steatohepatitis (NASH) sufferers of the accident at the Chornobyl NPP following the assessment of metabolic changes and control of persistent infections. MATERIALS AND METHODS: The study included 104 males with NASH, who were sufferers of the Chornobyl disaster and underwent examination and treatment in the conditions of the clinics of the National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine. Analysis of the course of the functional state of the liver before and after treatment with hepatoprotectors was carried out using laboratory methods of investiga tion. RESULTS: Hepatoprotectors of different groups used for the treatment of patients affected by the Chornobyl accident with NASH, differed in their effect on various chains in the pathogenesis of disease. Ursodeoxycholic acid (UDCA) drugs and preparations of holy thistle normalized the functional state of the liver and disorders of fat metabolism. Treatment with essential phospholipids eliminated cytolytic syndrome with a significant decrease in alanine amino transferase (p < 0.05), but increased alkaline phosphatase (p < 0.001), beta lipoproteins (p < 0.05), triglycerides (p < 0.05), the total cholesterol level remained elevated to (7.0 ± 0.8) mmol/L. Amino acid (AA) preparations normal ized the level of aminotransferases, eliminated the symptoms of cholestasis with a significant decrease in bilirubin (p < 0.001) and alkaline phosphatase (p < 0.001), positively influenced on fat and carbohydrate metabolism decreasing levels of beta lipoproteins (p < 0.05), triglycerides and glucose. Treatment with hepatoprotectors posi tively influenced on the state of antioxidant protection (AOP) - decreased before treatment in 56.5 % of patients, after treatment it reduced to 28.6 % (p < 0.05), the number of patients with elevated lipid peroxidation indices decreased from 39.1 % to 21.4 %. Titres of antibodies to persistent herpes virus infections, elevated before treat ment, under the influence of hepatoprotectors did not decrease to reference values. CONCLUSION: The most effective were drugs on the basis of AA, when applied they normalized the functional state of the, fat and carbohydrate metabolism, decreased lipoperoxidation and improved AOP state. Effect of drugs AA and UDCA on the level of antibodies to herpesvirus infection requires further study.

Peculiarity of prooxidant-antioxidant balance indicators in patients with nonalcoholic fatty liver disease who have been exposed to ionizing radiation due to the Chornobyl NPP accident. / OSOBLYVOSTI POKAZNYKIV PROOKSYDANTNO ANTYOKSY DANTNOI RIVNOVAGY U KhVORYKh NA NEALKOGOL'NU ZhYROVU KhVOROBU PEChINKY, IaKI ZAZNALY DII IONIZUIuChOGO VYPROMINIuVANNIa VNASLIDOK AVARII NA ChAES.

OBJECTIVE: To define the features of prooxidant antioxidant balance in patients with nonalcoholic fatty liver disease who have been exposed to radiation as a result of the Chornobyl accident. METHODS: using Indicators characterizing the processes of oxidative modification of macromolecules by blood lev els of compounds with isolated double bonds (CIDB), diene conjugates (DC) oxodiene conjugates (ODC), secondary products of lipid peroxiodation reacting with thiobarbituric acid, products of oxidative modification of proteins in blood serum by levels of neutral and basic 2,4 dynitrofenilhidrazones, superoxide dismutase and catalase content in erythrocytes and ceruloplasmin in plasma were determined for the diagnosis of oxidative stress. The factor of antiox idant state was calculated. RESULTS: In the absence of differences between the ratios between the primary and intermediate products of lipids peroxidation increasing relative content of DC and ODC in patients with nonalcoholic steatohepatitis (NASH), which suffered radiation exposure, was found compared with patients without nonalcoholic fatty liver disease (NAFLD) and NASH patients, who had no history of radiation exposure. This may be a manifestation of insignificant activation of lipid peroxidation and disturbance of LPO products transformation at different stages. In irradiated steatohepato sis (SH) patients, unlike SH patients who have not undergone radiation exposure,, the proportionalityof lipid perox idation products between the content of izopropanol phase lipid extracts of blood was violated, and Spearman cor relation coefficients between CIDB and DC and DC and ODC did not exceed the limits average values. In the group of patients with SH who suffered from radiation exposure level CIDB was slightly higher compared with patients with NASH. Regardless of whether there was a history of radiation exposure, the level of oxidative protein modification (OMB) products in NASH patients was higher compared with patients with SH, but the difference reached significant values only in the subgroup of non irradiated patients with NASH by 2.4 dinitrophenilhydrazones of neutral charac ter. Mean values ??of catalase activity in patients with NASH also exceeded the corresponding values of SH patient. The average values of the factor of antioxidant status in patients with both SH and NASH subjected to radiation exposure, were lower than in the corresponding subgroups of non irradiated patients by 29 and 21%, respectively. CONCLUSION: Existing dismetabolic disorders may contribute to the development of endogenous intoxication and deepening of pathological changes in the liver of NAFLD patients from SH to NASH.

Structure of comorbid diseases in patients with non-alcoholic fatty liver disease, exposed to ionizing radiation as a result of the Chornobyl NPP accident. / Struktura komorbidnoi' patologii' u hvoryh na nealkogol''nu zhyrovu hvorobu pechinky, jaki zaznaly vplyvu ionizujuchogo vyprominjuvannja vnaslidok avarii' na ChAES.

Objective - to study of the structure of comorbid diseases in patients with nonalcoholic fatty liver disease (NAFLD), exposed to ionizing radiation due to the Chornobyl accident, and in the groups of comparison. Materials and methods. Array of surveyed males was divided into 4 groups: the main group - 136 patients with NAFLD affected by the Chornobyl NPP accident, the first comparison group (І CG) - 28 affected by Chornobyl NPP accident without liver disease, the second comparison group (II CG) - 50 patients with NAFLD not exposed to factors of the Chornobyl disaster, and the third comparison group (III CG) - 16 unexposed persons without liver disease. Results. A significant amount of co-morbid pathology was found in all studied groups but III CG: at the average from 4.1 ± 0.4 diseases in II CG to 5.2 ± 0.2 in the main group of patients (p < 0.05), among which in 6.6-7.1 % of cases more than 10 diseases were established. The most common disorders were cardiovascular and cerebrovascular and endocrine diseases. Structure of comorbid pathology in NAFLD in the main study group differed from this in II CG by a significantly greater frequency of detection of cerebrovascular diseases (73.5 and 56 %, p < 0.05). As for features of the metabolic syndrome in Chornobyl accident sufferers essential hypertension (71.3 % ), discirculatory encephalopathy (48.5 %) and thyroid diseases (47.1 %) were more frequent than in II GC: correspondingly 58 % (p < 0.001), 28 %, (p < 0.01), and 30 %, (p < 0.05). Essential hypertension in only 35.7 % patients without NAFLD (I CG) was detected (71.3 % in the study group, p < 0.01), and chronic cerebrovascular insufficiency in 71.4 % (39.7 % in the study group, p < 0.01). Conclusion. Structure of comorbid pathology in NAFLD patients sufferers of the Chornobyl NPP accident was different both in a large number of identified diseases and nosological structure. The most common disorders were cardiovascular, cerebrovascular, and endocrine diseases. Significantly higher incidence of essential hypertension, vascular encephalopathy, and thyroid disease was determined.

Peculiarities of viruses Herpesviridae family persistence in patients with non-alcoholic fatty liver disease who had been exposed to the factors of Chornobyl NPP accident. / Osoblyvosti persystencii' virusiv rodyny herpesviridae u hvoryh na nealkogol''nu zhyrovu hvorobu pechinky, jaki zaznaly dii' faktoriv Chornobyl''s''koi' avarii'

Objective - to define the features of viruses persistence belonging to the Herpesviridae family in patients with non-alcoholic fatty liver disease (NAFLD) who had been exposed to the factors of Chornobyl NPP accident. Material and methods. The main group included 45 male NAFLD patients sufferers of Chornobyl NPP accident with absorbed doses of external irradiation in the range of 10-580 mSv. The group of nosology comparison consisted of 20 male NAFLD patients with the doses of irradiation within the limits of natural radiation background and regulated doses of medical irradiation. Antibodies to the viruses of herpes simplex 1/2 types (anti-HSV-1/2 IgG), cytomegalovirus (anti-CMV IgG) and Epstein-Barr virus (anti-EBV IgG) were determined by ELISA according to instructions of manufacturer. Results. There were no patients in both groups without IgG antibodies characterizing persistence of some Herpesviridae representative. Tendencies to the increase of antibodie levels to the viruses of herpes simplex, cytomegaly and Epstein-Barr in the seropositive patients, who had been exposed to the factors of Chornobyl NPP accident relative to the patients of group of nosology comparison were found. There were no differences between the subgroups of patients with steatohepatosis (SH) and nonalcoholic steatohepatitis (NASH) in the main group by anti-HSV-1/2 IgG and anti-CMV IgG levels while in the group of comparison SH patients had 60.5 % higher level of anti-HSV-1/2 IgG (p < 0.05) than NASH patients and anti-CMV IgG - 88.2 % respectively. Besides for NASH patients of main group anti-CMV IgG level exceeded 79.6 % (p = 0,02) analogical level for NASH patients in the group of comparison. The mixt infection by the viruses of 1/2 types herpes simplex and cytomegaly was most often determined in all groups with the direct correlation between the levels of anti-HSV-1/2 IgG and anti-CMV IgG. The markers of cytomegalovirus monoinfection were registered only in NASH patients both in main group and in the group of comparison. Conclusion. According to the presence of class IgG antiviral antibodies, NAFLD patients regardless of radiation influence in anamnesis have high prevalence of Herpesviridae family viral infection: herpes simplex 1/2 types, cytomegalovirus and Epstein-Barr virus. In the group of patients who had been exposed to the factors of Chornobyl NPP accident greater part of seropositive results and higher mean values of the probed antibodies titres were registered than in the groups of comparison. The mixt infection by the viruses of herpes simplex 1/2 types and cytomegaly was registered in most patients with existence of direct correlation between the levels of anti-HSV-1/2 IgG and anti-CMV IgG.

Comorbidity and radiation: methodological aspects of health assessment of persons exposed to the Chornobyl accident factors.

Comorbidity is one of the most challenging problems of a modern medicine. In a population exposed to the factors of the Chornobyl accident there is an obvious increase in the number of diseases occurring simultaneously against the background of rising prevalence of different classes of chronic medical nosology. The scientific data analysis are presented on the methodological approaches that can be used to create a specialized system for integrated assessment of the health of patients with comorbid disorders. Developing such a system it should be taken into account the trends of changes in the incidence, prevalence and structure of chronic disease, factors and regularities of comorbid disease in the cohorts of Chornobyl accident clean-up workers, evacuees and dwellers of contaminated territories. The system should provide a non-random selection of combinations (clusters) of the most common diseases with serious consequences for the survivors.