CLINICAL PHASES OF CHRONIC HEPATITIS B AMONG GEORGIAN PATIENTS.

Hepatitis B virus infection remains one of the major healthcare problems in Georgia with an exposure prevalence of 25.9% (Positive Anti-HBc) and chronic HBV infection (Positive HBsAg) 2.9%. Determination of clinical phase of chronic HBV infection is crucial for evaluation prognosis and accordingly, initiation of antiviral treatment, which might be lifelong. The specific aim of our study was to collect data on clinical characteristics of HBV-infected patients and determine the clinical phases of chronic HBV infection in the Georgian population. We randomly selected 111 chronic HBV-infected patients from the database of the medical center Mrcheveli. Liver fibrosis was assessed by Fibroscan, and viral load data were computed by the Real Time polymerase chain reaction (PCR) methodology. Liver fibrosis results were available for 74 of the patients (67%), and a majority of patients (72 of the 74, 97%) had no signs of advanced liver fibrosis. Viral load data were available for 94 patients, of whom 70 (74.5%) had an HBV-DNA level less than 2000 IU/ml, while 18 (19.1%) had an HBV-DNA level between 2000 and 20000 IU/ml and 6 (6.4%) were higher than 20000 IU/ml. Data for the assessment of the clinical phase of chronic HBV infection were available for 54% of patients (60 of the 111). Only 3.3% (2/60) of patients had undetectable HBV-DNA and 75% (45/60) had a viral load <2000 IU/ml. Two patients were HBeAg-positive, one of them with hepatitis and another with normal ALT. A few patients classified as HBeAg-negative with chronic hepatitis given normal ALT criteria: 3/60 (5%) by EASL and 6/50 (10%) patients by AASLD. In summary, 11/60 (18.5%) and 8/60 (13.5%) patients had HBV-DNA >2000 IU/ml but a normal ALT. Given the small number of patients, we cautiously conclude that most patients (75%) had HBeAg-positive or -negative chronic HBV infection without hepatitis. However, up to 19% of patients were not possible to classify in any of the internationally recognized phases of HBV infection. Patients within this indeterminate grey area, should be evaluated cautiously and management needs to be individualized. It will be interesting to evaluate the reason high viral load in HBeAg negative patients with normal ALT and long-term outcome among these patients (liver fibroses and/or HCC development).

DISTRIBUTION OF HBV GENOTYPES AMONG GEORGIAN PATIENTS OF DIFFERENT AGE GROUPS.

Hepatitis B virus (HBV) infection is one of the major healthcare problems in Georgia with a prevalence of 2.9% in the adult population. There is no published data on HBV genotype distribution among different age groups in the country. The study aims to evaluate genotype distribution in Georgian HBV-infected patients among different age groups. Data was extracted from the clinical database of Mrcheveli medical center. Genotyping was performed using INNO-LiPA methodology. Statistical analysis was done using the statistical software SPSS 23.0. The total number of patients enrolled in the study was 84, of which 52 (62.1%) were males. Participants were mostly from Tbillisi (63.2%, N=53). Even though HBV genotype D was more predominant (found in 57.1% (N=48) of study participants), than genotype A (found in 42.9% (N=36) of the study population). Age was significantly associated with genotype distribution. The majority of the participants (58.3%, N=49) were 35 years old or younger. Genotype D was predominant in 71.4% of the study participants older than 35 years old, versus 46.9% of individuals 35 or younger with genotype D (p<0.001). Genotype A, among those <35 and >= 35 was presented in 53.1% and 28.6% of cases, respectively. Our data suggests that HBV genotype D is most prevalent among older Georgian patients chronically infected with hepatitis B. More than half of younger patients (35 years old or younger) have Genotype A.

RESOLUTION OF NATIONAL ADVISORY BOARD.

On October 2, 2020, by Novo Nordisk initiative, an expert council was held in Tbilisi, Georgia, dedicated to the problems of introducing innovative insulin therapy on the example of insulin degludek into the clinical practice. The council chaired by prof. R. Kurashvili included seven leading endocrinology experts in Georgia and a specialist in the field of pharmaco-economics from Russian Federation Prof. A. Kulikov. During the expert council, important scientific, clinical and economic emphases were made on the benefits of using insulin degludec associated with its unique structure and mechanism of action. Special emphasis was placed on the difficulty in managing children and adolescents with type 1 diabetes. The meeting provided compelling evidence that insulin degludec reduces the incidence of hypoglycemia and diabetic ketoacidosis, thereby contributing to overall health and the prevention of vascular complications in children and adolescents with diabetes. The members of the council resolved to petition the Georgian Ministry of Health to include insulin degludek in the state program for children and adolescents with diabetes.

PROSPECTIVE OBSERVATIONAL COHORT STUDY OF PREDICTORS OF THE EFFECTIVENESS OF PEGYLATED INTERFERON IN PATIENTS WITH HEPATITIS C IN GEORGIA.

The main objective of the study was to evaluate the predictive values of virological response at 4th and 12th weeks after treatment initiation on sustained virological response by HCV genotype in patients with hepatitis C in Georgia. Local, non-interventional, prospective, cohort study was conducted in 2011-2016. A cohort of adult peginterferon treatment naïve patients with chronic hepatitis C were observed during the complete active treatment period with PEGASYS®/COPEGUS® and 24 weeks after the end of treatment. HCV RNA titers were assessed prior to treatment, after 4, 12 weeks of treatment, at the end of treatment and 24 weeks after the end of treatment.530 men and women aged ≥18 years with serologically proven CHC (all genotypes) were enrolled in this study. Enrolles study subjects were treated with PEGASYS® 180mkg (peginterferon alfa-2a) in combination with COPEGUS® 200mg (ribavirin) according to the current standard of care and in line with current summary of product characteristics. All clinical information for this cohort study was collected from the patient's medical records. All laboratory parameters which were collected for this observational study according to the protocol were performed in study centers. All data were analyzed with descriptive and analytical statistics. Our analysis demonstrated that the early achievement of viral response predicts the higher probability of achieving sustainvirul response. The viral response itself was strongly associated with baseline liver fibrosis quantitive HCV RNA level. Early starting of treatment determines the probability of achievement higher osustain viral response.

Cytokines and T regulatory cells in the pathogenesis of type 1 diabetes.

Type 1 diabetes (T1D) is an inflammatory disease of the pancreatic islet, in which insulin-producing ß-cells are preferentially destroyed to varying degrees by the concerted action of autoreactive T-cells and monocytic cells. Th1-type cytokines (IL-2 and IFN-γ) correlate with T1D, whereas Th2 (IL-4 and IL-10), Th3 (TGF-ß), and T regulatory cell-type cytokines (IL-10 and TGF-ß) correlate with protection from T1D. An altered balance between the proinflammatory and regulatory T-cell responses, in which T regulatory cells lose the battle, leads to T1D. The aim of current study was to determine the role of CD4+CD25+ regulatory T cells and cytokines: IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17 in pathogenesis of T1D.The study was carried out on 71 patients suffering from T1D at the department of endocrinology, Tbilisi State Medical University and Diabetic Children Association. The circulating levels of (IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17) were determined by ELISA according manufactures' protocol (R&D Systems Inc., USA). Tregs - CD4+CD25+ frequency was determined on cytofluorometer (BD FACSCalibur flow cytometer, USA). Statistical analysis was performed by using STATISTICA 8.0 for PC (Statsoft Inc., Minneapolis, USA) and Mann-Whitney U-test. Our study revealed significant decrease of IL-6, TNF-α, IL-10 and IL-4 plasma levels (1.197-, 1.188-, 1.504- and 1.840-times respectively) and increase of IL-17 plasma level (2.311-times) on the background of almost unchanged frequency of Tregs in patients with type 1 diabetes. In T1D patients CD4+CD25+ Tregs frequency did not correlate with diabetes duration and positivly correlated with age and IL-4. We supposed that decreased level of IL-4 and IL-10 reflects inhibited functional activity of these cells. We suggested that shifted balance of Th17/Tregs towards inflammatory IL-17 producing cells and decreased levels of suppressive cytokines IL-4 and IL-10 play crucial role in T1D. Future studies are needed to clarify changes in which subsets of heterogenous population of regulatory cells are associated with diabetes duration and how the therapy affects their frequency and function.

[Microbial structure of acute bacterial conjunctivitis].

Microbiological investigation of 124 patients with acute conjunctivitis which were treated in one of Tbilisi policlinics in 2010-12 years, was performed; microbial structure containing 124 microbial strains of different species was detected. Namely, following species of microorganisms were isolated: S. aureus - 35 strains (28,2%), Str. pneumoniae - 10 strains (8,1%), S. epidermidis - 6 strains (4,8%), Ps. aeruginosa - 24 strains (19,4%), Moraxella catarrhalis - 21 strains (16,9%), Haemophilus influenzae biogroup aegipticus - 17 strains (13,7%), and Klebsiella pneumoniae - 11 strains (8,9%). Identification of microorganisms was performed using classic methods of microbiological explorations and test systems API (bio Meriux). Study of sensitivity/resistance to antibiotics (ciprofloxacin, levofloxacin, tobramicin, norfoloxacin, moxifloxacin) containing in eye drops, was performed by diffusion in agar. High level of resistance to this antibiotic was found. As a result it is recommended to perform microbiological investigation in each case of acute conjunctivitis, to receive rational treatment.

[Antibiotic resistance of nosocomial strains of Staphylococcus spicies].

115 clinical strains of Staphylococcus spicies were isolated in 2005-2010 and investigated from patients with wound infections hospitalized in Tbilisi surgical clinics. Detection of sensitivity/resistance to several groups of antibiotics, was detected by serial dilution method on agar media. During the period of testing, was detected increase in 2-fold of meticillin-resistant St. aureus and in 3-fold of meticillin-resistant St. epidermidis strains. Important increase of resistant Staphylococcus strains was identified to aminoglycosides, macrolides, lincosamines, tetracyclines and ftorchuinolons. Investigated strains of staphylococci were characterized by 100% sensitivity to vancomycine and linezolid.

[Microbial spectrum of nosocomial pneumonia in traumatological patients].

In this article there are given results of microbiological investigation of nosocomial pneumonia agents, microbial structure. Investigation was held in 727 cases of traumatological patients treated because of hip replacement or osteosinthesis of limbs. Complications with nosocomial pneumonia was found in 27 cases (3,7%). In 27 cases of diagnosed pneumonia, 66 microbial strains were isolated. In 4 cases (14,8%) was detected mono infection, different microbial association were isolated in 23 cases (85,2%) - 2 microbes in 7 and 3 microbes in 16 cases. Microbial structure was presented by: S.aureus (27,3%), Kl.pneumoniae (19.7%), S. pneumoniae (15,2%), A. baumanii (10,6%), E. coli (4,6%), enterobacter spp. (9,1%), P. aeruginosa (13,6%). Study of sensitiveness/resistance of separated stains to different groups of antibiotics showed, that micro organisms have high level of resistance to antibiotics and also pan-resistance. So, success of antimicrobial therapy depends on prompt and correct choice of antibiotics, based on aetiology of infection and sensitiveness to antibiotics. In cases of empirical administration, it is necessary to use antibiotics with high level of activity against pneumonia agents - carbapenems, and in case of high probability of MRSA - it is better to use linezolid or vancomicin.

[Microbiological investigation of diabetic foot infections].

The aim of the article was to determine the structure of infections agents in diabetic foot infections and their sensibility to antibiotics A total of 295 microbial isolates were obtained from 115 patients with confirmed diabetic foot infection, treated in 2005-2009 years. Of these aerobes were found in 92.88%, anaerobes - in 7.12%. Microbal associations, various aerbal bacteria were found in 58,49% of cases, associations of aerobes with anaerobes - in 17.92% of cases; from 21.70% of patients were isolated microbial monocultures. The most common gram positive infect in diabetic foot infection was S. aureus, gram negative - P. aeroginosa. Methicillinresistent S. aureus were - 57,52%. In 95.57% of cases S. aureus strains were sensitive to vancomicin. Strains of P.aeruginosa were highly resistant to all investigated antibiotics. Enterobactericeae shown high sensitivity to karbopenemes (95.96%). It is concluded, that success of antimicrobial therapy depends on correct choice of antibiotic, based on in time exposal of etiology of infection, determination of its sensitivity to antimicrobial remedy, considering of its pharmacocinetical features.

Local blood flow in the dorsal hippocampus and cerebellar cortex in the offspring of iodine-deficient rats.

Experimental studies demonstrated that hypothyroidism can lead to depressive behavior and that thyroid hormones can have antidepressant effects. Postnatal changes in local blood flow in the dorsal hippocampus and cerebellar cortex were studied in the offspring of rats kept in conditions of iodine deficiency at conception and throughout gestation. The data obtained from these studies showed that severe limitation of iodine intake before and during gestation leads to marked deficiency in the blood supply to both of these brain structures, though the decrease in local blood flow in the dorsal hippocampus was more marked. Addition of iodine to the diet of females prevented this deficit of blood flow in both structures.

The hearing system under thyroid hypofunction.

The auditory system has been investigated in 50 patients with thyroid hypofunction. Hearing thresholds were estimated by the pure tone audiometry, PTA. The brief tone audiometry, BTA, was carried out, evaluating differences between thresholds of shorter and longer 1-kHz tonal stimuli, 20 and 200 ms, respectively. The objective studies were established by registrations of evoked otoacoustic emissions, EOAEs, and of auditory brainstem responses, ABRs. The thresholds of ipsilateral and contralateral middle-ear muscle acoustic reflexes, ARs, were also compared. By the PTA, sensorineural hearing loss was detected in 74.0% of cases. The BTA revealed disturbances of temporal summation of excitation in cochlear receptors in 26.0% of inspected subjects. The data of the EOAE mostly corresponded to those of the PTA. In some patients, however, the PTA demonstrated normal thresholds, while the EOAEs as well as the BTA indicated abnormalities. The ABR and AR procedures detected the central hearing disorders in 30.0% and 26.0% of the tested patients, respectively. The investigations have shown that the specific hormonal therapy hardly improves either peripheral or central hearing disorders associated with hypothyroidism.

[About correlation of dysfunction of the thyroid gland with fibrocystic diseases in women].

The reference data contain a lot of information on the interrelation between destroying of a thyroid gland and fibrocystic diseases. However contradictions in these data proves that this issue is not solved completely. The aim of the given study was the investigation of interrelations between frequency of occurrence of pathology of a functional condition of the thyroid gland and the frequency of occurrence of fibrocystic diseases. 90 women aged 23-50 were investigated. Concentration of thyroxin (FT4), thyrotrophic hormone (TSH), titers of antibodies to thyreoperoxidase, microsomal fraction of thyreocytes and thyreoglobulin were measured by ELISA. Palpation and ultrasonic investigations of thyroid and mammary glands were used, morphology of central formations of mammary glands according to indications was also carried out. A special questionnaire was completed for each patient. Our investigations showed that along with the declining of function of thyroid gland and the increased level of TSH in the blood, the risk of development of fibrocystic diseases is increased twice.

Growth hormone (GH) determinations by RIA and IFA during GH stimulation tests in children with short stature.

Growth hormone deficiency (GHD) as a syndrome comprises multiple pathogenetically distinct entities caused by disorders of secretion or peripherial action of growth hormone (GH). Confirmation of the diagnosis of GH deficiency in children is based on provocative testing for human growth hormone (hGH). Immunofunctional assay (IFA) allows quantitation of only biological active GH forms in circulation. The aim of this study was to compare the results of GH determinations by radioimmunoassay (RIA) and IFA, and to establish cut-off-levels for IFA in insulin tolerance test (ITT). We have investigated 32 children (30 males and 2 females) with short stature. All patients underwent insulin tolerance test (ITT), GH was measured in duplicate by radioimmunoassay (RIA, Seria) and IFA (DSL). Children with peak GH concentration below 10 ng/ml in ITT (by RIA) underwent arginin tolerance test (ATT, arginin 0,5 g/kg). The correlation between the results of growth hormone determination by radioimmunoassay and immunofunctional assay was excellent and cut-off-level in stimulatory test was established for the immunofunctional assay.

[Local blood flow in the dorsal hippocampus and cerebellar cortex in progeny of iodine-deficient rats].

Experimental studies show depressive behavior in rats caused by hypothyroidism and antidepressant effect of thyroid hormones. The present study analyses changes in the hippocampal and cerebellar cortex local blood flow in the progeny of rats suffering from iodine deficiency before mating and during the whole period of gestation. The diet with very low iodine content results in a decrease of local blood flow in both brain structures, but the greatest changes were observed in hippocampus. Addition of the iodine to the diet eliminates the above blood flow changes.

[Monitoring of level of antibiotic resistance of microbial strains, isolated in cases of surgical infections in period from 2003 to 2005 years].

Microbial structure of surgical infections and level of antibiotic resistance of microbial strains isolated in period from 2003 to 2005 years was investigated. As a result of performed investigation, 871 strains of different microbial species were isolated. It occurred that, in microbial structure of wound infections isolation of gram-positive microflora (509 strains) was 1,5 times higher than gram-negative (362 strains). Quantitative analisation has shown, that microorganisms were isolated in high amount, COU=10(5)-10(8). In 49% of cases microorganisms were isolated as microbial associations. In 37% of isolated microorganisms they had Nosocomial features. Investigation of sensitivity of microorganisms to antibiotics of all known group has shown tendency of rise of level of resistance even to modern antibiotics. It was found out Cephalosporins, Phtorhinolons and Karbapenems are showing good result. Basing on performed investigations could be recommended--strictening of strategy and control in use of antibiotics.

[Results of serotyping of strains isolated from patients with ulcerative colitis (colitis gravis), adaptive colitis and chronic catarrhal colitis].

Serotyping of 565 E.coli strains isolated from 273 patients with ulcerative colitis (70 patients); chronic catarrhal colitis (96 patients), adaptive colitis (107 patient) and of 72 E. coli strains isolated from 50 practically healthy persons (control group) was performed. Serotyping was performed in reaction of agglutination, on stage-glass, by use of commercial set consisting of O and H monovalent serum. As a result of performed investigation it was determined, that in patients with different intestinal inflammatory pathologies, there were found significant pathologic changes in intestinal microbiocenosis, in which main role are playing by strains of E. coli. Such violations of intestinal microbiocenosis often are leading to complications of basic disease. Serotyping of E. coli strains has shown, that in formation of pathologic microbiocenosis with more or less equal frequency are taking part enteropathogenic, enteroinvasive, enterotoxic strains of E. coli and also some definite serotypes of E. coli - representatives of normal intestinal microflora with ability of synthesis of thermolabile enterotoxin.

[Altered ability to learn of rat offspring with iodine deficiency].

Experimental data demonstrate that hypothyroidism could result in depressive behavior and subsequently thyroid hormones could act as antidepressants. Postnatal changes in learning ability, memory and emotional status in posterity of rats, which have experienced different level of iodine deficiency before conception and during all gestation period were investigated in this study. Results obtained suggest that sudden iodine deprivation before and during gestation led to a significant neurological defect, which was represented by loss of ability to learn, one of the most important functions of brain in newborn and by evidence of depression. Iodine supply to the diet of female rats eliminates these effects completely.

[Open field testing of the progeny of rats with iodine deficiency].

Experimental studies show depressive behavior of rats caused by hypothyroidism and anti-depressive effect of thyroid hormones. The present study analysis changes in emotional state of the progeny of rats suffered from iodine deficiency of different severity before mating and during whole period of gestation. The basic diet with low content of iodine markedly decreased animal's motor activity and that was clearly demonstrated in open field testing. More pronounced changes in open field behavior was observed in group of animals with more restricted iodine diet (addition of KClO(4) to the basic diet) -- animals show significant decrease number crossed squares, number of entering into central squares and vertical standings, and increased frequency of gumming. Addition of the iodine to the diet prevents development of the mentioned changes.

[The association of autoimmune thyroiditis with HLA-B8 in the Georgian population].

The study of distribution of HLA antigens among Georgian population in case of autoimmune thyreoiditis revealed a statistically significant association of HLA-B8 antigen with autoimmune thyreoiditis. For statistical analysis we used following criterion: relative risk, attributive risk, preventive fraction, correlation coefficient and immunogenetic correction (P). Without compatibility to these criteria, there were no associations of the HLA antigens with the diseases. Although 8 of the antigens gave relative risk more than one, but only HLA B8 gave real association with autoimmune thyreoiditis. Typing of HLA antigens of class I and class II loci was done by classic microlymphocytotoxic test. The test performed on the lymphocytes from patients with autoimmune thyreoiditis. The character of association of HLA antigens among Georgian population with Hashimoto disease differs in character from other populations that evidently can be explained by the distributional character of HLA antigens among normal Georgian population.

[Pathogenesis of diabetic lesions of the myocardium]. / O patogeneze diabeticheskogo porazheniia miokarda.

On the basis of both literature data and their own observations, the authors suggest the identification of various forms of diabetic cardiopathy in relation to the pathogenetic mechanisms of the development of this complication. The microangiopathic form of diabetic cardiopathy develops as a result of cardiac diabetic microangiopathy. Vegetoneuropathic cardiopathy arises secondary to the impairment of the cardiac performance neural regulation associated with damage to the parasympathetic and/or sympathetic innervation of the heart secondary to diabetic vegetoneuropathy. Diabetic metabolic cardiopathy is induced by diabetic disorders in myocardial metabolism. A combined form of diabetic cardiopathy results from the combined lesion of the heart under the impact of the above specific mechanisms.