Hepatocytic Apoptosis and Immune Dysfunction in Decompensation of Alcoholic Liver Cirrhosis with Different Grades of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1ß, IL-4, IL-6, and IL-8 were also assayed. As ACLF progressed from grade 0 to grade 3, the levels of cytokeratin-18 fragments, IL-6, and IL-8 significantly increased, while IL-4 decreased. TNFα peaked in ACLF grade 1, but decreased in grades 2 and 3. IL-1ß did not depend on the ACLF grade. Thus, hepatic damage and immune dysfunction are implicated in the progression of ACLF.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1ß, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1ß, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

[Hepatocellular damage and inflammation in various forms of alcoholic liver disease].

AIM: The aim of the study was to evaluate hepatocellular damage and immune inflammation in various forms of alcoholic liver disease (ALD). MATERIALS AND METHODS: 104 patients with ALD were examined: 15 (14.4%) with liver steatosis (LS), 19 (18.3%) with steatohepatitis and 70 (67.3%) with liver cirrhosis (LC); men 50 (48.1%), women 54 (51.9%); age 45.78.4 years. Traditional clinical, laboratory, instrumental studies were performed, the levels of fragments of cytokeratin-18 (FCK-18), cytokines IL-1, TNF-, IL-4, IL-6, IL-8 were determined by ELISA. The control group consisted of 39 healthy individuals: men 20 (51.2%), women 19 (48.7%), age 48.58.3 years. RESULTS: In LS, an increase in the level of FCK-18 was noted with normal aminotransferase activity, the content of TNF-, IL-6, IL-1, IL-8 increased and the level of IL-4 decreased compared to those in healthy individuals. In steatohepatitis, a triple increase in aminotransferases and FCK-18 was observed compared with LS, as well as an increase in the level of inflammatory mediators, to a greater extent IL-6, to a lesser extent IL-8, TNF-, a decrease in IL-4, IL-1 remained at the same level. In LC, there was a further increase in FCK-18, significantly more pronounced than an increase in AST, and the increase in cytokines continued to the same extent, the levels of IL-6 and IL-8, to a lesser extent IL-1 and TNF-, and the level of IL-4. CONCLUSION: With the progression of ALD from LS to steatohepatitis, hepatic cell damage was carried out by equally pronounced processes of hepatocyte necrosis and apoptosis, with the development of cirrhosis of the liver, parenchyma damage occurred mainly due to hepatocyte apoptosis. The immuno-inflammatory process progressively increased from the stage of LS to LC with IL-6 and IL-8 undergoing the greatest dynamics. FCK-18 can serve as a non-invasive marker of hepatic cell damage, and IL-6 and IL-8 markers of immune inflammation in ALD.

CHRONIC HEPATITIS WITH DOUBLE B/C INFECTION: VIROLOGICAL, CLINICAL, MORPHOLOGICAL CHARACTERISTICS.

AIM: To estimate the r, virological and clinical characteristics of chronic viral hepatitis (CVH) with double B/C infection. MATERIALS AND METHODS: We examined 282 patients with CVH. Genomes of hepatitis B virus (HBV) and hepatitis C virus (HCV) were studied by PCR in blood and liver (AmpliSens HBV and Amplisens HCV Russia), nuclear proteins (HBcorAg HBV and NS3 HCV) were determined by immunohistochemical method (Novocastra, UK), HBVgenome was sequenced by the Sanger method using ABI prism BigDye Terminator v3.1 kits and ABIPRISM 3100 analyzer (AppliedBiosystems, USA). Indices of histological activity (HAI), fibrosis, and portal vein (PV) congestion index (CI) were calculated by formula CI=SBB/LB V where S is P V cross section area in cm2 and LB V - linear blood flow velocity in cm/s (Vivid Pro- 7 apparatus, USA). RESULTS: CVH with double B/C infection was diagnosed in 85 (30.1%) patients including 44.7% with viral genomes and proteins in the live; 42.4% with HCVviremia, and 12.9% with HBJV/HCVviremia. Maximum CVH activity was documented in patients with latent HBV/HCVviremia (ALT 157.2±59.2 U/, HAI 11.6±1.3,fibrosis 2.8±0.7, C1 0.059±0.005); it was minimal inpatients.without viremia (Alt 76.25±63.0 U/I, HAI 6.7+-0.6,fibrosis 1.7±0.5, CI 0.042±0.001;p <0.05). Patients with latent HBV infection had precore/ore and pres/s mutations in HBVgenome and cytoplasmic localization ofHBcorAg. CONCLUSION: Double B/C infection was diagnosed in 30.1% of the patients with CVH dominated by HCV Patients with latent HBVhadprecore/ore and pres/s mutations. The highest intensity of hepatic cellular inflamation,fibrosis, and PV congestion was associated with HBV/HCV viremia and the lowest with intrahepatic localization of both viruses.

[DIAGNOSIS AND CLINICAL MANIFESTATIONS OF CIRRHOTIC CARDIOMYOPATHY].

UNLABELLED: The aim of the study was to determine the incidence of cirrhotic cardiomyopathy (CCMP), features of its recognition and clinical manifestations. MATERIALS AND METHODS: The study included 102 patients with alcoholic and viral liver cirrhosis (LC) without cardiovascular history, without viremia and signs of acute alcoholic hepatitis. Echocardiography, electrocardiography (ECG) and brain natriuretic hormone (proBNP) level were investigated in all patients. RESULTS: CCMP signs were detected in 65 (63.7%) of the 102 patients examined. All patients showed signs of electrophysiological myocardial abnormalities in ECG, signs of myocardial injury and the presence of heart failure in echocardiography, increase in proBNP. Interval QT length (0.4689 ± 0.012 s.) was significantly (p = 0.0461) higher than that of the control group. Violation of diastolic relaxation of the left ventricle was detected in 36 (55.6%) patients. The average level of proBNP was 540.85 ± 236.43 pg/ml, significantly different from the level of proBNP in healthy individuals--89.45 ± 26.43 pg/ml. The incidence of CCMP increased progressively with the severity of the Child-Pugh class and was 42.4% in patients of A class, 84.6% (p = 0.0132) in patients of B Class and 100% in patients of C class (p = 0.0219). The length of the QT interval, the proBNP level and frequency of diastolic dysfunction increased with increasing of liver cirrhosis severity. CONCLUSION: The frequency of detection of cirrhotic cardiomyopathy was 63.7%. More pronounced CCMP signs were observed in alcoholic liver cirrhosis than in viral. The frequency of detection and severity of cirrhotic cardiomyopathy progres sively increased with the severity of liver cirrhosis. Brain natriuretic peptide was the most sensitive indicator of myocardial damage in liver cirrhosis irrespective of its etiology.

[The role of different factors affecting the duodenum in chronic viral hepatitis B].

The aim of the present study was to determine the frequency and the character of duodenal lesions in patients with chronic viral hepatitis B (CVH-B), to elucidate the dependence of these parameters on the activity and duration of hepatitis, virulence, and portal blood flow. A total of 206 patients with CVH-B were examined. It was found that CVH-B was associated with the development of chronic duodenitis in 23.3% of the patients. Endoscopic studies revealed different degree of affection of duodenal mucosa. Superficial focal and moderately severe duodenitis occurred more frequently (in 33.3 and 37.5% of the patients) than manifest duodenitis (12.5%). Erosive duodenitis concomitant with Helicobacter pylori infection was diagnosed in 16.7% of the patients. The main factors contributing to the development of chronic duodenitis included viral infection, its intensity, duration of hepatitis, and disturbed portal circulation. Severity of duodenitis was closely related to the severity of CVH-B.

[The pancreatic lesions in chronic viral hepatitis B].

Sings of pancreas damage among 206 patients with chronic hepatitis B (CHB) appears in 45.1%: hyperamylasemia--in 18.9% patients, ultrasonography (USG) sings of pancreatic disorders--in 44.2%. Some parallelism was revealed between increasing of frequency and degree of pancreas damage and rising of CHB activity and viremia intensity. Pancreas USG can early revealed the symptoms of pancreas damage. Among all USG pancreas parameters in CHB changes of pancreas sound thickness appears more frequency, pancreas contours, sizes and structure changed more rarely.

[Use of enzyme substitutes in hypolactasia]. / Primenenie fermentnykh zamestitel'nykh preparatov pri gipolaktazii.

The paper presents the results of clinical and laboratory studies of lactrase, a drug containing lactase. This agent is recommended for splitting lactic sugar in subjects with appreciably decreased production of endogenous lactase (hypolactasia). Twenty-eight patients with this condition were examined. Manifest clinical symptoms of the condition were observed after loading with 50 g of lactose in all examinees. Addition of 250 mg of lactrase to lactose led to complete clinical compensation of the deficit of endogenous lactase in 75% examinees, and if 500 mg of lactrase was administered, hypolactasia was compensated in virtually all patients. A single intake of 50 g of lactose with lactrase causes a statistically reliable increase of glycemia in such patients. Moreover, a reliable effect of lactrase was observed when measuring galactose in the urine following the lactose test with 250 and 500 mg of lactrase. Our results indicate a high efficacy of lactrase in the treatment of patients with hypolactasia.