Alexander Yagoda

Risk factors of advanced fibrosis in non-alcoholic fatty liver disease, associated with type 2 diabetes mellitus | Koroy | Experimental and Clinical Gastroenterology Факторы риска тяжелого фиброза при неалкогольной жировой болезни печени, ассоциированной с сахарным диабетом 2 типа | Корой | Экспериментальная и клиническая гастроэнтерология

Aim of the investigation. To study the relationship of blood levels of vitamin D-binding protein (VDBP) with clinical and laboratory manifestations of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus. Materials and methods. The study included 80 patients with type 2 diabetes mellitus aged 33 to 69 years (67 women, 13 men). NAFLD was detected in 75.0% patients with type 2 diabetes mellitus. Severe liver steatosis was observed in 40.0% cases of NAFLD, fibrosis F3-4 in 23.3%. Serum levels of VDBP were determined by enzyme-linked immunosorbent assay. Results. The presence of NAFLD in patients with type 2 diabetes mellitus was characterized by lower blood levels of VDBP. Biochemical syndromes of liver pathology, as well as manifestations of diabetes mellitus (except for its duration) did not affect serum levels of VDBP in NAFLD. In patients with NAFLD and obesity, abdominal obesity or dyslipidemia, a lower concentration of VDBP in blood was determined. VDBP values did not depend on the presence of arterial hypertension and metabolic syndrome in NAFLD. Patients with severe liver steatosis or fibrosis F3-4 had lower blood levels of VDBP. Conclusion. Thus, in NAFLD associated with type 2 diabetes mellitus, there is a decrease of blood levels of VDBP, which is associated with the duration of diabetes, the presence of obesity, abdominal obesity and dyslipidemia. Cases of NAFLD with severe steatosis or severe fibrosis/liver cirrhosis are characterized by a lower serum concentration of VDBP.

A clinical case of lymphoid tumor hiding under the «mask» of recurrent polychondritis with high activity of inflammatory process and limited response to treatment is presented. In addition to auricle damage, the disease was accompanied by non-erosive non-deforming arthritis, tenosynovitis of the Achilles tendon with its rupture, episcleritis, nasal chondritis, skin lesions in the form of Sweet neutrophilic dermatosis, ascending aorta dilation, subclinical signs of lung and pericardial damage, and development of macrocytic anemia with normal blood levels of vitamin B12 and folic acid, absence of laboratory manifestations of autoimmunity. Despite the fact that recurrent polychondritis with similar clinical and laboratory signs may be part of the phenotype of recently described adult autoinflammatory syndrome (VEXAS), the determination of its genetic marker gave a negative result.

Cogan’s syndrome is a systemic vasculitis belonging to the group of variable vasculitis. It is characterized by damage to the eyes (interstitial keratitis) and the audiovisual system (sensorineural hearing loss, vestibular disorders), less often by the development of systemic manifestations (aortitis, neurological disorders). Systemic damage involving the eyes and audiovestibular apparatus requires differential diagnosis of a wide range of diseases, including Wegener's granulomatosis. The review provides detailed information on the etiopathogenesis, clinical picture, diagnosis, principles of therapy, and prognosis of this rare disease. The complexity of the diagnosis and treatment of Cogan’s syndrome highlights the need for an interdisciplinary approach to the management of such patients.

Aim of investigation. To study the prognostic significance of clinical and laboratory markers of liver pathology, including components of the matrix metalloproteinase (MMP) system, to identify moderate/significant activity in chronic liver diseases (CLD). Materials and methods. 76 patients with CLD of viral or alcoholic etiology aged from 18 to 64 years were examined. Minimal (histological activity index — HAI 1-3 points), minor (HAI 4-8 points), moderate (HAI 9-12 points) and significant morphological activity (HAI more than 12 points) were detected in 19 (25.0 %), 34 (44.7 %), 14 (18.4 %) and 9 (11.9 %) of cases, respectively. Enzyme immunoassay was used to determine the blood levels of MMP-1, MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and the of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. Results. According to multivariate logistic regression data, moderate/significant histological activity of CLD was associated with γ-glutamyltranspeptidase (GGT) (odds ratio (OR) 1.016; 95 % confidence interval (CI) (1.006-1.024), p=0.001), international normalized ratio (INR) (OR 1.079; 95 % CI (1.028-1.132), p=0.002), and TIMP-1/MMP- 9 ratio (OR 0.554; 95 % CI (0.380-0.809), p=0.002). The combination of these parameters had sensitivity of 82.6 %, specificity of 92.5 % and accuracy of 89.5 % in detecting HAI of 9 or more points. Conclusion. The increased values of GGT and INR, as well as a reduced ratio of TIMP-1/MMP-9, are independent risk factors for moderate/significant histological activity in CLD, due to their participation in the processes of hepatic inflammation.

Aim. To study the place and role of adhesive molecules (E-, L-, P-selectins, intercellular and vascular adhesion molecules of type 1 — ICAM-1, VCAM-1) in development of unfavorable one-year prognosis in young patients with acute coronary syndrome (ACS).Material and methods. A 12-month prospective follow-up included 95 patients (90 men, 5 women, mean age 41.00 [39.00-43.00] years) with ACS who underwent percutaneous coronary intervention (PCI). The endpoints were evaluated (primary — cardiovascular death, and combined secondary — nonfatal acute myocardial infarction and acute cerebrovascular accident, emergency hospitalization due to cardiovascular causes — unstable angina, arrhythmias, heart failure). Blood concentrations of E-, L-, P-selectins, ICAM-1, VCAM-1 were determined by enzyme immunoassay on the 1st (before PCI) and on the 7th day of hospitalization (after PCI).Results. During 12 months, 22 (23.16 %) patients had estimated endpoints: death in 2 (2.1 %) patients, nonfatal myocardial infarction in 6 (6.32 %), hospitalization due to unstable angina in 14 (14.73 %). In ACS patients with unfavorable annual prognosis, the levels of leukocytes, P-selectin and ICAM-1 on day 1 (before PCI), L- and P-selectins on day 7 (after PCI) were significantly higher than in patients with favorable annual period. According to multivariate analysis, predictors of unfavorable annual prognosis in young ACS patients were the levels of leukocytes (p=0.020) and ICAM-1 (p=0.010) on day 1 (before PCI) and L-selectin on day 7 after PCI (p=0.040).Conclusion. During the first 12 months in young ACS patients the most significant factors of unfavorable prognosis are the levels of blood leukocytes and ICAM-1 on day 1 (before PCI), and L-selectin on the 7th day after percutaneous coronary intervention.

Spondyloarthritis is a group of diseases involving the axial skeleton and sacroiliac joints, including axial spondyloarthritis or ankylosing spondylitis and peripheral spondyloarthritis. Spondyloarthritis is associated with an increase in cardiovascular morbidity and mortality, which may be the result of cardiac manifestations of disease or due to the accelerated development of atherosclerosis. The combination of two pathologies contributes to a more severe course of diseases and negatively affects the results of therapy, which indicates the relevance of this interdisciplinary problem. The review highlights data on cardiovascular morbidity and mortality in spondyloarthritis, the occurrence of various risk factors. The data on the relationship of cardiovascular pathology with activity and functional disorders in spondyloarthritis are presented.

Aim of the investigation. To study the significance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in combination with markers of liver pathology in predicting one-year mortality in patients with liver cirrhosis. Materials and methods. Over the course of one year of follow-up, 159 patients with liver cirrhosis aged 26 to 64 years were examined. The primary endpoint was assessed: death from any cause. The blood levels of MMP-1, MMP-9, and TIMP-1 were determined by enzyme-linked immunosorbent assay. Results. One-year mortality was 8.5% and it was associated with parameters of Child-Pugh score ≥8 points, C-reactive protein ≥15.5 mg/l, ESR ³12 mm/hour, gammaglutamyltranspeptidase ≥124 u/l, prothrombin index ≤77%, albumin ≤30 g/l, MMP-1 ≥24.2 ng/ml, MMP-9 ≥331 ng/ml, TIMP-1/MMP-1 ≤19.4, TIMP-1/MMP-9 ≤2.4, with the presence of alcoholic etiology, inflammatory syndrome, ascites 2-3rd degree. According to multivariate regression analysis, the independent factors of one-year mortality in liver cirrhosis were Child-Pugh score and TIMP-1/MMR-9 ratio. The combination of these signs in predicting a lethal outcome had a sensitivity of 92.3% and a specificity of 84.3% (AUC 0.890). Conclusion. Thus, Child-Pugh score and TIMP-1/MMP-9 ratio are predictors of one-year mortality in patients with liver cirrhosis, which reflects the severity of liver damage and the development of complications, as well as due to the participation of MMP-9 in inflammation and vascular remodeling.