Introduction. Biological properties of virus, such as susceptibility to antivirals, the clinical course of chronic hepatitis B (CHB), the probability of developing cirrhosis and hepatocellular carcinoma are determined by genotype and mutations in the genome of the hepatitis B virus (HBV).The aim of the study was evaluating of HBV genetic variants in patients with CHB from St. Petersburg hospitals.Material and methods. A total of 1414 CHB patients with positive polymerase chain reaction HBV genome in blood and/or liver tissue were observed. Genotype was determined in 298 patients, sequencing of the polymerase gene fragment was performed in 80 patients.Results. Viral DNA was detected in 323 (55.8%) patients with CHB. Genotype D was determined in 238 (80,1%), genotype A – in 49 (16,5%), C genotype – in 2 (0,7%) and mixed A+D – in 8 (2,7%) patients. Substitutions in YMDD-motif of the polymerase protein (M204I/V) as well as other primary and secondary resistance mutations to nucleotide analogues (lamivudine, telbivudine, entecavir) were found in four patients. Mutations in the reverse transcriptase (rt) region of polymerase gene were shown to affect the structure of surface protein. The substitution rtA181T in three patients resulted in formation of stop codon (sW172*) and premature termination of surface protein synthesis. The absence of HBeAg and the degree of fibrosis increase in 7 patients may be the result of mutations identified in core gene (G1896A, A1762T, G1764A).Conclusion. Study of the geographical distribution of HBV genotypes and identification of amino acid substitutions leading to decrease in serum markers concentration and emergence of resistance antivirals mutations is of great practical importance for predicting severity of the disease and effectiveness of antiviral therapy.

Description of two clinical cases of chronic HBV hepatitis at cirrhotic stage associated with type III cryoglobulinemia manifested with symptoms of systemic vasculitis is presented in current article. There were no signs of HCV infection in both patients. In first case cutaneous vasulitis appeared after 19 years since serological finding of HBsAg and vasculitis progressed despite steroid therapy. Initiation of antiviral therapy (entecavir 0.5 g/day) induced transient remission. After interruption of antiviral therapy vasculitis reappeared with several vasculitic ulcers on lower legs. Mild improvement of vasculitis was noted after repeated plasmapheresis, steroid and cytostatic treatment with addition of lamivudin. Despite therapy reactivation of HBV infection was detected. Lamivudin was changed to entecavir and rituximab was given in two 500 mg infusions. Combined antiviral and anti-CD20 treatment induced remission of cutaneous vasculitis and healing of leg ulcers. In other case vasculitis manifested after 21 years since detection of HBsAg with cutaneous purpura, arthritis and microhematuria. Entecavir 0.5 g/day induced rapid virological response and complete remission of symptoms related to vasculitis. Similar literature cases were reviewed and available treatment options in refractory cryoglobulinemic vasculitis were discussed.

One of the phases of the natural course of chronic hepatitis В is «HBsAg negative» phase, the clinical and prognostic significance of which is not defined yet. The frequency of HBsAg negative phase of chronic hepatitis В among the hospitalized patients of Clinical Infectious Diseases Hospital named by S.P. Botkin (Saint-Petersburg), for the period of 2010–2012 was assessed in this study. We analyzed the age structure of the patients, their clinical-laboratory inde[es and set the frequency of cirrhotic stage of disease. The «HBsAg negative» phase is revealed among quarter of patients with chronic hepatitis В the middle aged group (45–59 years old). The 84 (67,2%) hospitalized patients with HBsAg negative chronic hepatitis В diagnosed were given a diagnosis of cirrhotic stage disease. Thus, the spontaneous clearance of HBsAg from blood serum is not always the evidence of the prognostically favorable course of chronic hepatitis B.

In our study, 155 patients with chronic hepatitis B viral load was analyzed and its relationship with some of the results of laboratory and instrumental examinations. Found that half of the patients had a viral load of 4-5 log copies/ ml and above. In HBe-negative patients, the viral load is lower than in patients with HBeAg. The level of viremia had a direct correlation with the activity of ALT and AST, and eedback to the level of blood platelets. In patients with a viral load of more than 5 log copies / ml, significantly higher ALT, AST and GGT, as well as the level of red blood cells, whereas platelet counts were significantly lower than in patients with viremia <5 log copies/ml . Platelet counts inversely correlated with age. In 11% of patients with chronic hepatitis B over 40 years, had platelet counts below normal. The level of viral load and ALT and AST is straight, and the level of blood platelets inverse correlation with the severity of liver fibrosis. In patients without evidence of liver fibrosis (F0) viral load was significantly lower than in patients with signs of fibrosis of the liver at any stage of its formation.

In our study, 155 patients with chronic hepatitis B viral load was analyzed and its relationship with some of the results of laboratory and instrumental examinations. Found that half of the patients had a viral load of 4-5 log copies/ ml and above. In HBe-negative patients, the viral load is lower than in patients with HBeAg. The level of viremia had a direct correlation with the activity of ALT and AST, and eedback to the level of blood platelets. In patients with a viral load of more than 5 log copies / ml, significantly higher ALT, AST and GGT, as well as the level of red blood cells, whereas platelet counts were significantly lower than in patients with viremia <5 log copies/ml . Platelet counts inversely correlated with age. In 11% of patients with chronic hepatitis B over 40 years, had platelet counts below normal. The level of viral load and ALT and AST is straight, and the level of blood platelets inverse correlation with the severity of liver fibrosis. In patients without evidence of liver fibrosis (F0) viral load was significantly lower than in patients with signs of fibrosis of the liver at any stage of its formation.

Patients with chronic virus hepatitis (32 patients, 13 with chronic hepatitis B and 19 with chronic hepatitis C) ages from 20 to 72 with elevated levels of bilirubin and active alanine aminotransferase, aspartate aminotransferase, gamma- glutamyl transpeptidase, received ursodeoxycholic acid (Urdoxa) over the course of 12 weeks. During therapy alanine aminotransferase, aspartate aminotransferase, bilirubin and gamma-glutamyl transpeptidase levels decreased. Urdoxa demonstrated good tolerance, efficacy and no visible side effects. Thus, Urdoxa could be used in treatment of chronic viral hepatitis with cytolytic and cholestatic syndromes.