Aim of investigation. To estimate the role of polymorphic variants of genes IL4 (C-590T), IL4RA (I50V), TNF (G-308A) and SLC11A1 (D543N) in chronic viral hepatitis progression. Material and methods. Overall 121 patients with chronic viral hepatitis C and B. Results. Study results have demonstrated, that of all investigated polymorphic variants of genes IL4 (C-590T), IL4RA (I50V), TNF (G-308A) and SLC11A1 (D543N) in patients with chronic liver diseases of various etiology the «Val/Val» IL4RA gene variant (II50Val) is associated with HBV-infection chronization. The allele «A» gene TNF-α (G-308A) is protective for chronic viral hepatitis and is associated with a low level of production by mononuclear cells of TNF-α and IL-12, high secretion of IL-4 and low degree of collagenopathy in the liver. Genotype «CT» of IL4 (C-590T) gene is an adverse marker for progression of chronic viral hepatitis B. There was significant correlation of polymorphic variants TNF (G-308A) and IL4 (C-590T) genes with production of the key interleukins, that determine type of immune response (Th-1, Th-2) and products of collagen metabolism that testifies genetic determination of system immune response and collagen formation processes in the liver at chronic viral hepatitis.

In a prospective non-randomized comparative open, parallel-group study evaluated the clinical efficacy of succinic acid on the impact on symptoms of anxiety and depression in patients with acute exacerbation of COPD and severe. A total of 134 patients. All subjects men 5168 years. The survey was conducted according to the criteria GOLD 2011. To assess the level of anxiety and depression questionnaire used HADS depression and samooprosnik CES-D. Patients in group 1 (n=61) standard therapy exacerbation. Patients in Group 2 (n=72), the standard therapy was supplemented with acute drug Amber-antitoks within 14 days, 1 tablet (0.5 g) 3 times daily after meals. Between groups were compared indicators characterizing COPD before and after treatment. The positive effect would be achieved in both groups. Patients whose treatment included succinic acid reached higher levels in relation to the comparison group: FEV 1p=0.01; FVCp=0.01; distance traversed in the test with the 6-min walk p=0.003; oxygen saturation after the 6-minute walk test p=0.0001; expiratory pressure at the mouth p=0.01; decreased symptoms of anxiety p=0.003; manifestations of depression decreased p=0.0001. It is concluded that succinic acid is included in the standard treatment of exacerbations of COPD, severe effective for relief of elevated levels of anxiety and depression. This effect is largely associated with improved somatic condition of patients after treatment. This is evidenced by the correlation between the level of anxiety and depression prior to treatment with the clinical manifestations of COPD exacerbations. In particular, the FEV1 (r=-0,72; p=0,01), with the distance traveled by a 6-minute walk test (r=-0,61; p=0,001); with oxygen saturation after 6 minutes walk test (r=-0,77; p=0,001); with expiratory pressure in the oral cavity (r=-0,53; p=0,01), with the oxygen saturation (r=-0,69; p=0,01).

Проведено 3-летнее обсервационное проспективное исследование по оценке прогностической значимости показателей алкогольного анамнеза у 203 больных циррозом печени алкогольной этиологии. Группы умерших и выживших больных за одинаковые периоды наблюдения сравнивались по суточной дозе алкоголя, суммарной (за все годы) дозы принятого алкоголя и частотам (режимам) приема алкоголя. Статистически значимые отличия в сравниваемых группах получены только по показателям частоты приема алкоголя. Более частый режим приема алкоголя связан с повышенной летальностью цирроза печени. Это обусловлено трудностью определения суточной дозы алкоголя больными, которым легче вспомнить частоту употребления алкоголя, чем его количество. Наличие энцефалопатии (печеночной и алкогольной) у данной категории больных осложняет процесс определения суточной дозы употребляемого алкоголя и является основной причиной ограничения использования данного показателя при прогнозировании выживаемости больных алкогольным циррозом печени. По нашим данным, в клинической практике наиболее высокую значимость в прогнозе выживания больных алкогольным циррозом печени с признаками энцефалопатии (печеночной и алкогольной) имеет анамнестическое определение частоты приема алкоголя.

Objective: to study influence of age and sex on the survival of patients with cirrhosis of viral and alcoholic etiology. For realization of the objective conducted cohort study with the inclusion of 249 patients with cirrhosis of viral (B, C, B+C), alcohol and mixed (alcohol+virus) etiology with the assessment of the ultimate solid point occurrence of death from cirrhosis or its complications. Age of patients from 17 to 75 years (Me=50 years), 114 men and 135 women. Observation period amounted to 47 months. For all the time of observation died 119 patients. It is established that the chances of dying in men with cirrhosis class C of Child-Pugh are 2.2 times higher than in women. Statistically significant differences began to be defined about 3 months of observation. This may be due to the best compensatory abilities of the female body. Because patients were at different stages of the disease for a correct estimation of the influence of age on survival was held stratification of patients according to the classes of Child-Pugh of cirrhosis and a correlation of age and the time prior to death studied within each class of cirrhosis. Not statistically significant effect of age of the patients with cirrhosis on survival.

In comparative, prospective, non-randomized cohort study the frequency of hospital relapse of infectious COPD exacerbation was evaluated in patients hospitalized with non-infectious exacerbation of the disease; typical spec-trum of sputum microflora for hospital exacerbations of COPD was defined. It was found that 57 % of patients hospitalized with non-infectious type of COPD exacerbations demonstrated relapse of infectious type exacerbation by 10–16 day of hospitalization in which initiation involved nosocomial microorganisms: Pseudomonas ae-ruginosa, Klebsiellapneumoniae (ESBl), Acinobacterboumonii, St. aureus (MRSA), Klebsiellaoxytoca (ESBL), E.coli (ESBL), Citrobactercoseri, Stenotrophomonasmaltophilia, Morganellamorganii. Multidrug-resistant mi-croorganisms in patients with hospital exacerbation of COPD were more common than in patients with commu-nity-acquired COPD exacerbation (45 % and 18 % respectively). The assigned antibiotic therapy for hospitalized patients with non-infectious exacerbation did not prevent the aggravation of hospital infection.

С целью изучения прогностической значимости уровня альфа-фетопротеина крови при циррозе печени проведено 3-летнее проспективное, когортное исследование с включением 107 больных циррозом печени вирусной (В, С, В + С), алкогольной и смешанной этиологии. За время наблюдения умерли 43 больных. Получено отсутствие статистически значимых различий уровня альфа-фетопротеина крови в группах умерших и выживших больных циррозом печени в периоды наблюдения от 1 до 36 месяцев. Также не получено статистически значимых различий уровня альфа-фетопротеина крови между группами больных циррозом печени различных этиологических вариантов, но одного класса по Чайлду-Пью. Методом анализа 95 % доверительных интервалов уровня альфа-фетопротеина между классами цирроза печени по Чайлду‒Пью определен пороговый уровень АФП (5,96 МЕ/л), превышение которого ассоциируется с развитием декомпенсации цирроза печени (чувствительность 0,58; специфичность 0,81). Не получено статистически значимых корреляций уровня альфа-фетопротеина с активностью индикаторных ферментов цитолиза − АсАТ и АлАТ, что позволяет сделать вывод о том, что повышение уровня альфа-фетопротеина в основном обусловлено стадией цирроза печени, а не его активностью.

A new method of predicting the probability of death in individual patients with liver cirrhosis or its complications, by determining serum levels of AST and creatinine duringone, three and six months. There has been conducted the cross-sectional prospective study of the 249 patients with viral liver cirrhosis, alcoholic and mixed etiology aged from 17 to 75 years in the stage of decompensation. The period of observation was from 10 days to 57 weeks. The patients were divided into 2 groups (deaths and survivors).

Изучена ассоциация делеционного полиморфизма генов глутатион-S-трансфераз GSTT1 и GSTM1 и однонуклеотидного полиморфизма A313G гена GSTP1 с заболеваемостью циррозом печени (ЦП) и выживаемостью больных в течение 4-летнего периода наблюдения. Исследование проведено на группе больных, проживающих в городе Томске и Томской области. Показано, что “нулевой” генотип гена GSTM1 является протективным фактором развития ЦП алкогольной и смешанной (вирусы гепатита C и B, алкоголь) этиологии. Частота “нулевого” генотипа гена GSTM1 в объединенной группе больных ЦП (без разделения по этиологическому фактору) составляет 39.2%, у больных алкогольным циррозом – 39% и при заболевании смешанной этиологии (HCV или HBV + алкоголь) – 34.2%, что значительно ниже, чем в контрольной группе (64.6%). Выявлено, что делеционный полиморфизм гена GSTM1 и вариант A313G гена GSTP1 коррелируют с выживаемостью больных ЦП. Так, частота “нулевого” генотипа GSTM1 в группе выживших больных выше (46.6%), чем в группе умерших (30.2%). Кроме того, в группе выживших частота генотипа АА гена GSTP1 выше, а генотипа AG ниже по сравнению с умершими за тот же период (63.1 против 40.5 и 31.1% против 51.2% соответственно). Выживаемость больных ЦП за 4-летний период в 2.5 раза выше у носителей генотипа АА гена GSTP1, чем у носителей GG и AG генотипов, и в 2 раза выше у пациентов с “нулевым” GSTM1 генотипом по сравнению с носителями этого гена. Вероятность летального исхода в течение 4 лет у гетерозигот AG (A313G) гена GSTP1 в 2.3 раза выше, чем у носителей гомозиготных генотипов AA и GG.

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

We tested the association of deletion polymorphism in the GSTT1 and GSTM1 genes for glutathione S-transferases and the A313G single-nucleotide polymorphism in the GSTP1 gene with cirrhosis morbidity and 4-year survival rate among residents of the Tomsk region, West Siberia. The homozygous deletion of the GSTM1 gene (null genotype) proved to be a protective factor against alcoholic and mixed (viral and alcoholic) liver cirrhosis. The frequency of this genotype in patients of the combined group having cirrhosis of any etiology was 39.2%, in patients with alcoholic cirrhosis it was 39.0%, and in patients with mixed cirrhosis it was 34.2%. This genotype was much more frequent among patients of the control group: 64.6%. The GSTM1 null genotype and the GSTP1 A313G polymorphic variant correlated with survival rate. The survivors had a higher GSTM1 null genotype frequency than the dead patients, 46.6 and 30.2%, respectively; a higher frequency of the GSTP1 AA genotype, 63.1 and 40.5%; and a lower frequency of the GSTP1 AG (A313G) genotype (31.1 and 51.2%). The survival rate in patients with the GSTP1 AA genotype was 2.5 times as high as in GG or AG genotype carriers. In patients with the GSTM1 null genotype, the survival rate was twice as high as in patients without the deletion. The 4-year fatal case probability in patients having the heterozygous GSTP1 AG genotype was 2.3 times higher than in patients with the homozygous AA or GG genotypes.

AIM:To study a relationship of the plasma activity of elastase-like and collagenase-like proteinases and their inhibitors to hepatic collagen metabolism and to detect the serum markers of fibrosis severity.SUBJECTS AND METHODS:Three hundred and fifty-nine patients with chronic liver diseases (CLD), including 118 patients with chronic viral hepatitis (CVH), 113 with CVH concurrent with alcoholic liver disease (ALD), 109 with ALD, and 19 with CLD in the presence of opiomania were examined. The activities of alpha1-proteinase inhibitor and alpha2-macroglobulin (alpha2-MG) were determined by the unified spectrophometric assay from the inhibition of N-benzoyl-arginine ethyl ester hydrolysis. The activity of elastase-like proteinases was determined by enzymatic assay from the hydrolysis of the synthetic substrate N-butyloxycarbonyl-L-alanine-para-nitrophenyl ester. That of collagenase-like proteinases was determined, by using a collagen type 1 substrate and expressed in terms of micromoles of the resultant hydroxyproline. The content of hydroxyproline was determined by a color reaction with demethylbenzaldehyde, a free, peptide- and protein-bound hydroxyproline; their fraction was obtained under various conditions of plasma protein isolation and hydrolysis. Plasma fibronectin levels were measured by solid-phase immunoassay. Liver biopsy specimens were morphologically studied in the majority of patients to determine the histological hepatitis activity index and the stage of fibrosis.RESULTS:Fibrois formation in the liver in its chronic diseases was attended by a significant reduction in the activity of collagenase-like proteinases hydrolyzing collagen and by the lower activity of alpha2-MG, an inhibitor limiting collagen formation.CONCLUSION:The identified changes make themselves evident just in early fibrosis, which suggests the rapid onset of imbalance in the mechanisms responsible for regulation of connective tissue synthesis and promotes intensified fibrosis formation.

Article presents the modern data on pathogenesis of portopulmonary hypertension and hepatopulmonary syndrome, its clinical value, classification and diagnostics. Significance of endogenic substances of liver dysfunctions in development of pulmonary blood flow disorders has also been considered.

An original method of proximal gastrectomy was used to eliminate hemorrhage from gastric and oesophagal varicose veins in 27 patients with portal hypertension. The follow up period varied from 1 to 23 years. The risk of hemorrhage and the degree of vein dilatation were assessed by endoscopy and endoscopic ultrasonography. It is concluded that the method used in the study may be recommended as the first-line surgery for the management of hemorrhage from gastric and oesophagal varicose veins with good functional results in the late postoperative period and rare complications.