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Aim: To define the role of DNA-methyltransferases of type 1 and type 3A in hepatitis B viral cycle., Material and Methods: Human hepatoma cells HepG2 with stable expression of 1.1-mer HBV genome were transfected with vectors encoding DNA-methyltransferase 1 (DNMT1), DNA-methyltransferase 3A (DNMT3A) or were co-transfected with these vectors. Total HBV DNA copy number, relative expression of pregenomic RNA (pgRNA), S-protein-encoding RNA (S-RNA) and cccDNA were analyzed by quantitative and semi-quantitative real-time PCR-analysis with TaqMan probes for assessment of DNMTs-mediated effects on HBV., Results: DNMT1 and DNMT3A suppress HBV transcription and replication, though to different magnitude. cccDNA pool is enlarged statistically significantly ≈2-fold (P<0.005) after transfection of DNMT3A, but is unaltered under DNMT1 treatment., Conclusion: DNMT3A regulates the size of cccDNA pool and is important for persistency of HBV infection.

Studied hepatotropic activity remaxol and Essentiale N with chronic viral hepatitis (hug) and: 45 patients received the drug remaxol (intravenous drip, 400 ml per day, 10 days), 45 patients Essentiale N (intravenous bolus, 5 ml per day, 10 days). The efficacy was assessed by clinical symptoms, activity ofAlt, AST, bilirubin, alkaline phosphatase, molecules of average weight (MSM), and total effective concentration of albumin (ECA). Remaxol when hug had a hepatotropic effect comparable with Essentiale N, but more effectively cut short asteno vegetative, dyspeptic, cholestatic and intoxication syndrome, which was confirmed by the significantly low values of MSM and high rates of ECA. The inclusion remaxol in the treatment of patients hug should be considered pathogenetically justified, clinically justified and promising.

Aim: To detect changes in the concentration of nitric oxide and its metabolites--nitrites and nitrates in conjunction with the indices of the glutathione system in the children with chronic hepatitis B and C., Patients and Methods: In the research took a part 76 patients (boys or girls) with chronic hepatitis B and C aged from 7 up to 16 years. Nitric oxide and its metabolites determined by method of V.A. Metel'skaya and N.G. Gumanova; level of reduced glutathione - the titrimetric analysis; activity of glutathione transferase - the method of spectrophotometry., Results: The content of nitric oxide and its metabolites--nitrites and nitrates--in serum and urine of children with chronic viral hepatitis B and C have increased. Correlations were revealed between nitric oxide and its metabolites in serum and urine, as well as between these indices and glutathione system parameters-reduced glutathione concentration and activity of enzymes of glutathione transferase of erythrocytes and plasma., Conclusions: In the children with chronic viral hepatitis B and C the increase of the concentration of nitric oxide and its metabolites in serum and urine is accompanied by decrease of reduced glutathione concentration and increase of glutathione transferase activity in erythrocytes and plasma. These findings suggest the presence of oxidative stress due to which the therapy should be strengthened by antioxidant effect.

The efficacy of the use of triple schemes in combined therapy of chronic virus hepatitis was estimated and its safety was monitored. The problems of therapy of mixed hepatitis in drug addicts are discussed. Immunotropic agents, increasing the efficacy of the standard therapy of chronic affections of the liver, are suggested to be used as the third remedy in the combined therapy.

The conformational structure of peripheral blood lymphocyte membranes was studied in children with chronic hepatitis B (CHB). With moderate and severe CHB activities, an exacerbation is characterized by the higher microviscosity of all layers of membrane structures with a preponderance of impairments in the plasma membranes, which is important in the mechanisms of disease progression. The relationship of the change in microviscosity to the severity of the process suggests that this indicator might be used as a prognostic criterion.

Chronic viral hepatitides (CVH) run with long-term activation of the system of mononuclear phagocytes associated with hyperproduction of active oxygen forms. This can be considered as risk factors of antioxidant insufficiency which determines the course of the disease. Now, antioxidant, cytoprotective medicines are more and more actively used in hepatology. The results are reviewed of many Russian clinical trials of efficacy of metabolic correctors based on siccine acid (reamberin, remaxol) as pathogenetic treatment in CVH. Metabolic correctors in combined treatment of CVH improve basic clinico-laboratory indices, raise efficacy of basic therapy, correct insufficiency of antioxidant defense. The results of the studies confirm advantage of antihypoxic medication over standard infusion therapy for treatment of CVH patients.

Aim: To study porphirin metabolism in chronic viral infections of the liver., Material and Methods: The examination of 101 patients with hepatic viral infections diagnosed chronic HCV-infection in 30 patients, chronic HBV infection in 25 patients and combined infection in 6patients. Patients with chronic alcohol intoxication were not included in the trial. Urinary uroporphirin and coproporphirin (CP), fecal protoporphirin and CP were estimated. Total porphirines were calculated., Results: 29 patients with chronic viral hepatitis had no porphirin disbolism. The latter (elevation of porphirine fractions in the urine and/or feces) was detected in 11 (84.6%) of 13 patients with hepatic cirrhosis (HC). Biochemical syndromes of elevated fecal porphirines, secondary coproporphirinuria, chronic latent hepatic porphiria were developing. The above disorders progressed with aggravation of the disease severity. In manifest late skin porphiria chronic HCV infection was detected in 19 (32.2%) of 59 patients., Conclusion: In non-alcoholic patients with chronic diffuse diseases of the liver of viral etiology nonspecific disturbances of porphirine metabolism develop at the stage of arising HC and are registered more frequently in the presence of chronic HBV-infection. Frequent combination of chronic HCV-infection with manifest late skin porphiria suggests a trigger role of HCV initiating specific disbolism of porphirines in this disease.

The aim of the study was to measure plasma levels of stable metabolites of nitric oxide, nitrates, and nitrites (NOx) in patients with chronic viral hepatitis and evaluate the possibility of their correction by low-power laser irradiation. NO metabolites (total nitrites and nitrates) were measured colorimetrically from the development of colour in the reaction of nitrite with sulfanilamide diazotization in Griess reagent. Colour intensity was determined with Victor2 enzyme immunoanalyzer, Perkin Elmaer (Finland). The patients were divided into three groups. In group 1 (control, n = 30) they received combined medicamentous therapy, in group 2 (n = 45) medicamentous therapy and a course of intravenous laser therapy, in goup 3 (n = 45) medicamentous therapy and skin laserotherapy. The results indicate that medicamentous treatment of patients with chronic hepatitis does not bring any beneficial changes in plasma NOx whose levels are significantly improved in case of simultaneous laser therapy. It is concluded that different laserotherapeutic modalities have beneficial effect on NO-producing function of endothelium and thereby improve its functional state. Compensation of NO deficit by laser therapy ensures overall protection of the organism against free radicals and decreases severity of oxidative stress.

The parameters of lipids, which reflect the morphological manifestations of hepatic damages of alcoholic, viral, and mixed viral-and-alcoholic genesis, were determined. The serum lipid spectrum was studied in 50 alcoholic patients without viral hepatitis markers, in 30 patients with chronic viral hepatitis B (CVHB), and in 40 with CVHB concurrent with alcoholism. Puncture biopsy of the liver and a histological study of its biopsy specimen were made in 47 patients. Total lipid levels above 9.0 g/l were the most typical biochemical marker of alcoholic damage to the liver; lysophosphatidylcholine (LPC) levels below 7% were a marker of its viral damage; total lipid levels above 9.5 g/l and LPC levels below 5% were a marker of its viral-and-alcoholic damage. Thus, serum lipids may be used as biochemical markers of the morphological manifestations of hepatic damages of various genesis.

The researchers evaluated the condition of lipid peroxidation and antioxidant protection system together with biochemical, immunological and morphological values in 117 patients with chronic hepatitis (CH) in virus replication phase (28 patient had CH type B, 66--CH type C and 28--CH type B+C), and estimated the importance of their interrelations to the prediction of disease outcomes.

The properties of ecdysten, an exdysterone-based preparation, were studied under experimental (of heliotrine induced hepatitis model in rats) and clinical (chronic viral hepatitis B) conditions. A 2-week treatment with ecdysten in a daily dose of 5 mg/kg (p.o.) significantly improved the state of rat liver, as manifested by normalization of the enzymatic activity of blood serum, stimulation of the protein and glycogen synthesis, inhibition of lipid peroxidation, and activation of all chains of microsomal oxidation of hepatocytes. The inclusion of ecdysten into a complex therapy scheme for patients with chronic viral hepatitis B (5-mg tablets twice per day over a period of 30 days) substantially improved the clinical and biochemical indices of the functional state of liver, positively influenced the humoral and cell immunity and the resistance factors, and normalized the course of autoimmune processes accompanying the liver pathology.

The aim of the study was assessment of hepatocyte apoptosis depending on expression of Fas and FasL proteins by various liver cells in patients with chronic viral hepatitis B (CVHB) or chronic viral hepatitis C (CVHC). The symptoms of hepatocyte apoptosis were observed in 3 of 12 patients with CVHB and in 9 of 14 patients with CVHC, the proportion of apoptotic cells being 12-65%. Hepatocytes of healthy people and patients with hepatitis B or C express Fas protein in the cytoplasm diffusely, as granules or on cell membrane. In health, hepatocytes do not express FasL, but in CVH they do. The highest apoptosis was observed in Fas protein location as granules in cytoplasm or in their preferable location on the cell membrane. The severity of hepatocyte apoptosis in CVH directly correlated with FasL expression by the cells of the lymphoid-histiocytic infiltrate in the liver and inversely correlated with FasL expression by hepatocytes. Thus, a great part of hepatocytes in CVH are killed by the virus; Fas/FasL interaction is leading in damage to hepatocytes in CVH.

There was a study of lipid peroxidation activity, ceruloplasmin level, bile acids content, and the liver detoxifying function state in 37 patients with chronic hepatitis types B and C of viral etiology. Changes of the indices under study were most apparent in patients with HCV. It was revealed that the degree of impairment of detoxifying and bile-producing functions of the liver are closely interrelated to the activity of the inflammatory reaction and lipid peroxidation processes. The increasing ceruloplasmin level in this category of patients hampers the reduction of the activity of lipid peroxidation processes, which is apparently related not only to the direct cytotoxic viral effect but also to the negative effect of superoxide ions on the cell membrane. Along with this, in cases of viral lesions of hepatocytes there are changes in the synthesis and conjugation of bile acids leading to the derangement of their correlation, their increased aggregate content and accumulation in tissues, which can also enhance the intensity of destruction of liver tissues and is an extra factor contributing to the intensification of lipid peroxidation processes.

We have studied the effect of dietary supplement "ExPress" on clinical and biochemical parameters and on the activity of detoxification enzymes of liver in patients with chronic viral hepatitis B and C. 24 patients (19 females and 5 males aged 16-39 years) were enrolled in the study. Patients in case group received dietary supplement "ExPress" in addition to basic treatment. Average indices of total bilirubin in cases after treatment were 26.98 +/- 2.85 mmol/l, while in controls--34.31 +/- 5.72 mmol/l (p > 0.05). Average indices of alanin-aminotransferase and aspartate-aminotransferase were 78.75 +/- 11.25 and 160.75 +/- 23.67 units while in controls--208.5 +/- 56.4 and 330.25 +/- 65.14 units respectively (p < 0.05). In case group we observed full normalization of thymol test--from 9.99 +/- 1.51 to 4.03 +/- 0.73 units (p = 0.001), while in controls--from 7.9 +/- 1.56 only to 5.2 +/- 1.15 units (p = 0.194). Contents of non-metabolized antipyrine in cases decreased from 9.76 +/- 1.2% (p = 0.0002) whilst in controls--from 9.38 +/- 1.28% only to 3.93 +/- 1.18% (p = 0.01). Results of the study show that dietary supplement "ExPress" induces the activity of detoxification enzymes of liver and increases the efficiency of basic treatment.

The nosologic and etiopathogenetic structure of the cholestatic syndrome encountered both in surgical and therapeutical practice is described.

A trial of a novel hepatoprotective plant drug lochein (Salsola extract) developed in Russia was performed in 110 patients with a verified chronic hepatitis of viral (73 patients) or alcohol (36 patients) etiology versus well-known hepatoprotector corsil given to 40 patients. Lochein demonstrated more potent effect than corsil.