[Evaluation of the effectiveness of ultrasound shear elastography and liver steatometry].

Detection of liver fibrosis and steatosis at early stages is a difficult task for clinical practice, due to the lack of early signs in routine radiation diagnostics. AIM: To evaluate the efficacy of ultrasound shear elastography and ultrasound steatometry of the liver with the use of domestic ultrasonic diagnostic system Angiodin-Sono/N-Ultra. MATERIALS AND METHODS: 264 people held ultrasound elastography and ultrasound steatometry. 38 patients underwent percutaneous puncture liver biopsy and subsequent pathophysiological examination. RESULTS: High correlation of fibrosis obtained at the Angiodin-Sono/N-Ultra and the leading ultrasonic systems with shear elastography was revealed. Cross-sectional comparative analysis of elasticity with the results of liver steatometry was conducted. CONCLUSIONS: Results obtained in all groups correlate with the data obtained in studies on Fibroscan. When working with system Angiodin we got a simultaneous comparative analysis of elasticity with the results of liver steatosis. Results appear to be much more stable and compact than those obtained in studies on the Fibroscan. A new diagnostic criterion was revealed the phenomenon of independence of fibrosis and steatosis indices.

[The Diagnostic Importance of Circulating MicroRNA for Non-Alcoholic Fatty Liver Disease (review of literature).]

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases in the world. The biopsy is required to confirm the diagnosis but due to its invasiveness, this procedure is not suitable for the massive screening. There are laboratory criteria of primary medical examination of the patients who are suspected to have NAFLD that allow diagnosing the pathological process, but these criteria do not comply with clinicians' requirements. At the same time, it is crucial to identify the patients in the initial stages of NAFLD. Recently, the attention of the scientists was concentrated on the research of the mechanism of NAFLD development and new diagnostic approaches. Accumulating results of this research show that NAFLD development is regulated with epigenetic factors, including microRNAs family (microRNA, miR), that may have high diagnostic and prognostic value. In this review, data extracted from PubMed are used to discuss the potential role of microRNA in the liver lipid metabolism and fatty liver disease. The possibilities of micro RNA (miR-16, miR-21, miR-34a, miR-103, miR-122, miR-145, miR-192, and others) use as prospective biomarkers for low-invasive NAFLD diagnostic, evaluation of steatosis activity and fibrosis score and stages, and prognostic markers of the disease are reviewed. This research discusses the analytical characteristics, benefits and possible limitations of their use in the clinical practice. The preliminary data allow claiming that some microRNAs are extremely perspective low-invasive diagnostic instrument and further research is required to investigate the impact of certain microRNAs in the pathogenetic mechanism of NAFLD development.

[PROGNOSTIC VALUE OF THE COMBINATION OF BLOOD GROUP SPECIFICITY AND INTERLEUKIN 28B GENE POLYMORPHISM FOR ESTIMATION OF EFFICIENCY OF THERAPY WITH THE USE OF PEGYLATED INTERFERON α-2 AND RIBAVARIN IN PATIENTS WITH CHRONIC GENOTYPE 1 HEPATITIS C].

AIM: To estimate the prognostic value of the combination of blood group specificity and interleukin 28B gene polymorphism for the achievement of sustained virologic response (SVR) to antiviral therapy (AVT) with the use of pegylated interferon α-2 and ribavarin in patients with chronic genotype 1 hepatitis C (CHC-1). The secondary aim was to evaluate the influence of these genetic factors on the progress of hepatic fibrosis in case of failure of the above treatment. MATERIALS AND METHODS: A total of 146 patients with CHC-1 were examined. We studied the RNA genotype of hepatitis C virus, blood group specificity, IL-28B gene polymorphism, and severity of hepatic fibrosis (puncture biopsies). Dynamics of hepatic fibrosis was followed up in 40 patients who failed to develop the virologic response. 20 control patients did not receive AVT. The multifactor significance criterion was used to identify the initial factor that produced the highest effect on SVR. RESULTS: SVR was observed in 56.8% of the patients. Its efficiency was most significantly influenced by. the combination of blood group specificity and interleukin 28B gene polymorphism (p = 0.000024). Combination of blood group (0)1 with C/C or T/T IL-28B genotypes, A(II) with C/T or T/T and B(III) with T/G was associated with SVR in 100, 88.2, and 94.4% cases respectively. It was absent in patients with blood group A(II) in combination with double-nucleotide substitution in rs8099917 of the IL-28B gene (TG and GG genotypes); these patients suffered progressive fibrosis. SVR occurred in 83.8% of the patients with blood group B(III). CONCLUSION: The knowledge of blood group in patients with CHC-1 and IL-28B gene polymorphism treated with the use of pegylated interferon α-2 and ribavarin allows to predict SVR with a probability of 100% in case of blood group 0(1) and C/C or T/T genotypes, 88.2% in case of blood group A(II) and single-nucleotide C>Tsubstitution in rs8099917 locus of the IL-28B gene, 94.4% in case of blood group B(II) and single-nucleotide T>G substitution in the rs809991.7 locus, 83.8% in case of blood group B(III). Treatment of patients with these genetic traits with antiviral drugs of direct action has no appreciable advances over treatment with AVT in combination with pegylated interferon α-2 and ribavarin (SVR above or around 85%). Patients with blood group A(II) and single- or double-nucleotide substitution in rs8099917 (TG or GG genotypes) have minimal chances to produce SVR to the above treatment. Simultaneous progression of hepatic fibrosis suggest that such therapy is undesirable in these cases. They should be regarded as main candidates for interferon-free therapy. Combination of blood group specificity and interleukin 28B gene polymorphism is a simple and reliable predictor of SVR and dynamics of fibrosis in patients with CHC-I receiving AVT with pegylated interferon α-2 and ribavirin; also, it may be an instrument of selection of patients for interferon-free therapy.

[Challenges and advances in diagnostics, prevention and treatment of hepatorenal syndrome].

Hepatorenal syndrome (HRS) is an exclusion diagnosis in patients with decompensated liver cirrhosis. True hepatic functional insufficiency is sometimes unobvious. Differential diagnostics of HRS encounters difficulty despite new diagnostic criteria. HRS can be prevented by the correct treatment of portal hypertension and hepatic insufficiency under careful monitoring. Effective conservative therapy may significantly change the short-term prognosis and facilitate remission in selected patients. Terlipressin is the agent of choice for HRS therapy aimed at the promotion of intrahospital survival for the subsequent referral of the patient to liver transplantation.

[The balance of markers of regulation vascular tone and fibrinogen in the prognosis of hemorrhagic transformation and fatal outcome in the acute period of ischemic stroke].

The markers of regulation vascular tone, such as rennin, endothelin-1, and C-type natriuretic peptide, are of great value for prognosis of hemorrhagic transformation and fatal outcome of ischemic stroke. A change in the vascular tone in case of hemorrhagic transformation at the affected site precedes activation of the coagulation component of hemostasis as a mechanism preventing blood loss and increasing fibrinogen level. This work was aimed to study the balance of the above markers and fibrinogen in the prognosis of hemorrhagic transformation and fatal outcome in the acute period of ischemic stroke. It included 62 patients receiving no thrombolytic therapy. It was shown that symptomatic hemorrhagic transformation was associated with elevated rennin levels without a marked fall in the level of C-type natriuretic peptide and asymptomatic hemorrhagic transformation with elevated endothelin-1 levels and decreased concentration of natriuretic peptide. Fibrinogen level on day 4 of the observation proved to be a reliable predictor of negative prognosis. Asymptomatic hemorrhagic transformation without fatal outcome was associated with systemic and local vasoconstriction and inhibition of local vasodilation. Symptomatic hemorrhagic transformation with the fatal outcome was accompanied by dysregulation of vascular tone in the form of activation of systemic and local vasoconstriction, insufficient inhibition of local vasodilation and compensatory reaction in the form of activation of hemostatic mechanisms manifest as elevated fibrinogen levels on day 4. The lethal outcome without hemorrhagic transformation was associated with systemic vasoconstriction, activation of local vasodilation and vasoconstriction leading to local "biochemical paralysis" of vascular tone regulation.

Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response.

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

[Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia and neighboring countries].

Allele and genotype frequencies for the locus encoding apolipoprotein E, involved in the regulation of lipid metabolism (APOE), were evaluated in 16 populations representing 12 ethnic groups (a total of 1103 subjects) from Russia and neighboring countries. In the populations examined, the frequencies of allele epsilon4, which is the risk factor of Alzheimer's disease and coronary heart disease, varied from less than 5 to more than 20%, while the variation of the major epsilon3 allele in these populations ranged from less than 75 to 95%. The frequencies of alleles epsilon3 and epsilon4 were 0.714 and 0.205 in Saami, 0.734 and 0.149 in Maris, 0.841 and 0.122 in Evenks, 0.788 and 0.163 in Buryats, 0.764 and 0.202 in Chukchi, 0.875 and 0.075 in Iranians, 0.956 and 0.044 in mountain-dwellers of the Pamirs, 0.771 and 0.094 in Ukrainians, and 0.795 and 0.091 in Belarussians, respectively. In Russians from different regions of the country, the frequencies of these alleles were 0.728 and 0.139 (Kostroma), 0.795 and 0.105 (Moscow), 0.857 and 0.092 (Rostov-on-Don), and 0.824 and 0.083 (Krasnodar), respectively. The latitudinal distribution of the APOE epsilon3 and epsilon4 allele frequencies in the populations examined was comparable to the frequency distribution pattern of these alleles in other populations of Eurasia.

[Alcohol-induced arterial hypertension and genetic polymorphism of alcohol-metabolizing enzymes].

AIM: To study arterial pressure (AP) and heart rate (HR) in patients suffering from alcohol withdrawal syndrome (AWS) with relation to genetic polymorphism of alcohol dehydrogenase-2 (ADG2) and aldehyde dehydrogenase-2 (AlDG2). MATERIAL AND METHODS: AP and HR were analysed for 36 alcoholics (83 hospitalizations, including repeated ones) with genotypes ADG2 and AIDG2 at admission to and discharge from narcological hospital. RESULTS: ADG2 genotypes distribution was the following: ADG2-1/1--61.1% (n = 22); ADG2-1/2--36.1% (n = 13); ADG2-2/2--2.8% 9n = 1). All the patients had a genotype AIDG2-1/1. A hypertensive reaction occurred in 75.9% inpatients with AWS. At admission, patients with genotype ADG2-1/1 had significantly higher systolic AP and HR vs those with allele ADG2-2: 146.6 +/- 17.0 mmHg against 141.2 +/- 14.9 mmHg, 95.6 +/- 13.9 b/min vs 88.5 +/- 12.2 b/min, respectively. In homozygous genotype ADG2-1/1 AP and HR were higher than in heterozygotes: SAP 152.3 +/- 12.9 mm Hg vs 145.2 +/- 16.2 mm Hg, pulse pressure 57.2 +/- 11.9 vs 50.0 +/- 15.1 mm Hg, HR 96.8 +/- 13.4 b/min vs 87.7 +/- 12.0 b/min. The groups had similar mean diastolic pressure. At discharge, AWS standard therapy resulted in a significant lowering of AP and HR in the study group. Mean values of the parameters in groups with different genotypes did not differe at discharge. CONCLUSION: Population of alcoholics from the Moscow Region had allele polymorphism ADG2. Genetic polymorphism AlDG2 is not typical for this group. Hypertensive reaction was registered in the majority of alcoholics in AWS. Higher systolic, pulse pressure and heart rate were significantly higher in the AWS group with genotype ADG2-1/1. Controlled alcohol withdrawal entails a significant reduction of AP and HR.

[Alcohol pathology in a general hospital]. / Alkogol'naia patologiia v bol'nitse obshchego profilia.

Screening of chronic alcohol intoxication (CAI) based on parallel use of test-questionnaires (CAGE, PAS-questionnaire) and assessment of organic evidence of alcohol abuse were employed in a clinicoepidemiological case-control survey covering 1191 patients aged 16-91 years admitted to a general hospital. 3335 autopsy protocols were analysed by pathoanatomical and forensic-medical criteria of CAI. It was found that CAI, directly or indirectly, raises risk of a wide spectrum of internal diseases which, according to ICD-10, are not directly related to alcohol. Each 5th hospitalization was caused by CAI sequela. Combined use of tests-questionnaires and consideration of physical stigms of CAI are proposed for screening of alcohol abuse and latent alcoholism in general medical practice. The authors think it necessary to establish addictological service at large general hospitals.

[Morphological characteristics of chronic hepatopathy in combination of HCV and chronic alcoholic intoxication]. / Morfologicheskie osobennosti khronicheskoi gepatopatii pri sochetanii HCV-infektsii i khronicheskoi alkogol'noi intoksikatsii.

Biopsies from 35 patients and autopsy material from 20 patients who died of chronic hepatopathy were studied. Hydropic dystrophy and inflammation were predominant in HCV infection. Chronic alcoholic intoxication (CAI) was characterized by diffuse large-droplet fat dystrophy and liver fibrosis. In combination of HCV-infection with CAI sclerotic processes were pronounced and therefore liver cirrhosis is more frequent than in other groups.

[Acute malignant myocarditis and pleurodynia as the manifestation of a probable Coxsackie B viral infection]. / Ostryi zlokachestvennyi miokardit i plevrodiniia kak proiavlenie veroiatnoi virusnoi infektsii Koksaki B.

The authors describe a 45-year-old female patient suffering from rapid-progressing myocarditis with growing disorders in conduction, repolarization alterations and heart dilatation seen for 3 days. The patient died on the 10th day of the disease which started from fever and catarrhal phenomena. Attack-like pains in the right half of the chest and abdomen, removable by narcotics, were a remarkable disease manifestation. The diagnosis of myocarditis was verified morphologically. The disease may be interpreted as infection with Coxsackie B virus associated with myocarditis and pleurodynia.

[The viral and immunological characteristics of cardiomyopathies and myocarditis]. / Virusoimmunologicheskaia kharakteristika kardiomiopatii i miokarditov.

As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.

[Epstein-Barr virus infection and congestive cardiomyopathy (serologic and immunomorphologic aspects)]. / Infektsiia virusom Epshteina-Barr i zastoinaia kardiomiopatiia (nekotorye serologicheskie i immunomorfologicheskie aspekty).

In serums of patients with congestive cardiomyopathy (CCM), patients with ischemic heart disease (IHD) and those of healthy subjects, presence of antibodies to capsid and early antigens of Epstein-Barr's virus (EBV) and to various structural components of myocardium was determined in order to study seroepidemiologic relations between the infection and CCM as well as immunopathogenic reactions against myocardium in this disease. Seroepidemiologic relation between EBV and CCM consisted in significant (compared to healthy subjects and patients with IHD) increase in average geometrical titres of antibodies to virus-associated antigens. Half of the patients with CCM had active EBV infection proved by presence of antibodies to early EBV antigen. Antibodies to various structural components of myocardium were found, including those to myocardial nervous fibers (for the first time) in 1/3 of the patients. Etiological role of active EBV infection in development of lymphomas during the post heart transplantation period in CCM as well as in myocardial nervous fibers damage in this disease is also discussed.