The aim of review. To draw attention of general practitioners to the risk factors of hepatocellular carcinoma (HCC) development, to define group of patients with high probability of development of this tumor, to outline algorithm of screening diagnostics for patients of high risk group.

Original positions of the report. Independent risk factors for HCC development include hepatitis B and C viruses, the level of hepatitis B viral load, the stage of liver cirrhosis, male gender, age over 40 years, alcohol intake and smoking. Patients of high risk group should undergo investigation of alpha-fetoprotein level and abdominal US once per 6 months for early diagnostics of HCC; at detection of any liver lesions further deep investigation including computer and magnetic-resonance tomography, guided biopsy of the lesion is indicated.

Conclusion. According to present studies data, morbidity of HCC all over the world steadily grows. High risk group for HCC include patients of male gender over 50 years old (for Caucasian patients) with liver cirrhosis, especially of viral etiology, smoking and consuming alcohol. Prophylaxis of HCC should include prevention of hepatites B and C viruses infection, elimination of hepatotoxic substances, hepatitis B virus vaccination, antiviral therapy for patients with hepatites B and С. Patients from HCC risk groups need to be screened for tumor regularly (once in half a year). Its detection at the early stage allows to start medical actions in time, that helps to increase patients’ survival rate.

The aim of review. To analyze efficacy of antiviral therapy of various duration in patients with chronic hepatitis C (CHC).

Original positions of the report. According to published data viremia dynamics has important prognostic value during treatment, which allows to consider it as one of important factors determining duration and efficacy of treatment along with virus genotype. Poor efficacy of the latter, especially at patients with the 1-st HCV genotype, high cost and risk of the serious undesirable effects cause necessity to individualize antiviral therapy at CHC, improve risk/benefit ratio.

Conclusion. At CHC patients with the rapid virologic response (absence of viremia at the 4-th week) it is possible to limit duration of treatment by pegilated interferon and ribavirin in the case of the 1-st HCV genotype to 24 wks, in the case of the 2 and 3-rd genotypes to 12–16 wk. In patients with the 3-rd HCV genotype without rapid virologic response and in patients with the 1-st HCV genotype and slow virologic response treatment probably should be prolonged to 48 and 72 wks respectively.

The aim of review. To estimate safety and efficacy of prescription of nucleoside analogues the patient with liver cirrhosis in an outcome of chronic hepatitis B.

Original positions of the report. Rates of progression of persistent HBV infection to liver cirrhosis stage depend on several factors – spectrum of viral markers, immune status of the patient, his/her age, gender, genetic predisposition, etc. Lamivudine has capacity for prolonged and persistent block of HBV replication. Its antiviral effect limited basically by development of drug resistance of a virus as a result of mutant strains development. Terms of lamivudine treatment for patients with liver cirrhosis should be no less than 22 months, and clearance HBV DNA is achieved in 93,9 % of patients. Sustained virologic response (it was assessed in 4 years after termination of treatment course) is estimated as 39%. Entecavir has higher (in comparison to lamivudine) efficacy in relation of supression of HBV virus replication and achievement of non-detectable level of viral load. The biochemical response in the group of cirrhotic patients at entecavir application is obtained at 63% НВеAg-positive and at 78% of НВеAg-negative patients. The virological response (supression of HBV replication) at entecavir treatment was: at НВеAg positive – 91%, at НВеAg-negative – 96%. The rate of histological response in the group treated by entecavir was significantly higher, than in group treated by lamivudine: in НВеAg-positive – 80 and 64%, in НВеAg-negative – 75 and 60% respectively.

Conclusion. At application of entecavir on a background of supression of viral replication the main strategic goal of antiviral therapy - regression of necroinflammatory changes in the liver at patients with HBV-viral cirrhosis is achieved.

The aim of review. To present modern data on the mechanism of action and clinical utilization of immunomodulating agent «Timosin alpha-1».

Original positions of the report. Timosin alpha1 is 28-base acetylated polypeptide, that effectively modulates human immune system and has direct action on the cells infected by virus that allows to talk of its «double» mechanism of action. Immunomodulating effect of Timosin alpha-1 consists in increase of natural killer cells number, CD4 and CD8 by stimulation of stem cells differentiation and decrease of T-cells apoptosis, and also in driving of immune response to Th1 subtype by increase of Th1 cytokines (IL-2, IFN) amount and decreases of amount of Th2 cytokines (IL-4, IL-10). Direct antiviral mechanism of Timosin alpha-1 consists in increase of expression of major histocompatibility complex molecules of the 1st class on infected cells and direct suppression of virus replication, and also in elevation of endocellular level of glutathione. Combination of Timosin alpha-1 and interferon-a (IFN-a) induces substantial increase of IL-2 level and blocks elevation of IL-10 level invoked by IFN-a that can be successfully utilized in chronic hepatitis B (CHB) treatment. Results of metaanalysis of 4 randomized controlled studies in which efficacy of Timosin alpha-1 and IFNб was compared in treatment of CHB (total number of patients – 199) were published. It is shown, that Timosin alpha-1 efficacy is increased eventually and is more pronounced at the end of monitoring period after termination of therapy. According to original studies The Asian-Pacific association for the study of the liver (APASL) included Timosin alpha-1 in the list of immunomodulating agents for CHB treatment besides standard and pegilated interferon-a (PEG-IFN-a). Efficacy of Timosin alpha-1 was demonstrated in the treatment of one of the most difficult groups of patients with persistent hepatitis C virus infection – non-responders at combined treatment by interferon and ribavirin. Timosin alpha-1 can be applied at immune antineoplastic therapy, in particular in treatment of hepatocellular carcinoma which is related to a final stage of persistent infection of hepatitis B and C viruses, that, as a rule, develops on a background of liver cirrhosis and in Caucasian patients.

Conclusion. Timosin alpha-1 is successfully applied in clinical practice in treatment of chronic viral hepatites B and C, as antineoplastic immunomodulating drug and requires further active studies.

Aim of investigation. Studying of efficacy and safety of the combined therapy of chronic hepatitis C (CHC) by pegilated interferon α-2а in combination to ribavirin at early stages of chronic hepatitis and HIV-infection at patients receiving no high activity antiretroviral therapy (HAART), and comparison of these data with results of treatment of patients with HCV monoinfection.

Materials and methods. Overall 50 CHC patients with HIV-infection at subclinical stage (stage 3–47 patients) and stage 4А of secondary diseases in remission phase without HAART (3 patients), as well as 49 CHC patients without HIV-infection – the 1st and 2nd groups respectively, were enrolled to the study. Pegilated interferon α-2а and ribavirin were prescribed to patients according to body weight for 48 wks irrespective to virus C genotype at combined HIV/CHC infection and for 24–48 wk in relation to virus C genotype – to CHC patients. The study had open, non-randomized, retrospective and prospective design.

Results. The rate of achievement of sustained virologic response as a result of therapy of CHC at the HIVinfected patients is comparable to that for CHC patients without HIV-infection. Tolerability of combined therapy was satisfactory at the majority of patients. The most common adverse laboratory manifestations were thrombocytopenia, leukopenia and neutropenia which did not require cessation of treatment. Ten patients of 1st group (20%) dropped from the study, including 6 (12%) patients that were excluded because of development of side effects. The basic causes for cessation of therapy were depression and long-term fever. During treatment significant decrease of CD4+ lymphocyte number took place, however no clinical signs of HIV-infection progression has been found.

Conclusions. Antiviral therapy at combined HIV/CHC infection should be prescribed to all patients from the moment of establishment of diagnosis of chronic hepatitis while patients require no HAART. It is recommended to carry out treatment of CHC at HIV-infected patients by pegilated interferon a-2а in combination to ribavirin which dose should be adjusted to body weight of the patient.

Aim of investigation. To determine pattern of changes of prevalence, and outcomes of alcoholinduced liver disease at inpatients and relation of these changes to consumption of alcohol in the country at retrospective investigation.

Materials and methods. For the years 1946–2005 2621 patient with liver cirrhosis (LC) were investigated, including 1362 patients with alcohol-induced liver cirrhosis (ALC) and acute alcoholic hepatitis (AAH) on a background of LC. The study also included 115 patients with AAH on a background of alcoholic steatohepatitis and 232 patients with hepatocellular carcinoma (HCC). Comparison group included 517 patients with acute viral hepatitis (AVH).

Results. Sixfold increase of alcohol consumption by the USSR-Russia population for 1946–2006 resulted in 8,5 times increase of number of ALC patients for specified interim, whereas the total number of patients with LC increased 4,1 times. During the years of limited sale of alcohol (1985–1989) the LC-related mortality decreased 2,6 times in comparison to previous five years. In 1996–2005 the number patients, died of alcohol-induced cirrhoses considerably exceeded this score for viral cirrhoses (104 and 36 respectively). Nevertheless, due to improvement of treatment the mortality at alcohol-induced cirrhoses in 2001–2005 decreased by 18%, but at HBV LC and especially at HCV LC these scores decreased in greater degree. In 1993- 2000 517 AVH patients were observed, of them lethal outcome developed at 11 (2,1%), of 127 AAH patients 24 died (18,9%). From 1992 to 2005 the proportion of alcohol-associated HCC increased by 58%. The brief comparative characteristic of main clinical and morphological nosological forms of alcohol-induced liver disease is presented. Facts on incompetence of myths, justifying alcohol abuse, are put forward.

Conclusion. Dominating growth of ALC is marked. In the years of limited sale of alcohol the number of LC with lethal outcome dramatically decreased. At the last decade the number of ALC patients with lethal outcome apparently exceeded similar figure for viral LC. Mortality rate for AAH in comparison to AVH patients was much higher.

Aim of investigation. To estimate of clinical efficacy and safety profile of parenteral form of «Phosphogliv» preparation containing glycyrrhizin and essential phospholipids, at treatment of patients with alcoholic liver disease.

Materials and methods. Overall 106 patients with chronic alcohol-induced liver diseases were investigated, diagnosis was verified by standard methods with obligatory assessment of the expert in narcology. Patients were randomized by random sample method in two groups: I group (n=58) – an abstinence in combination to placebo (intravenous injection 20 ml of normal saline solution 2 times per week), II group (n=48) – abstinence in combination to intravenous injection of 2,5 g of phosphogliv 2 times per week. Total period of observation was 104–106 wks on the average. Basic biochemical parameters, liver morphology and data of US-investigation were estimated.

Results. Before treatment the level of transaminases was: ALT 89,3±12,9 IU/l and AST 124,3±26,7 IU/l (I group), 78,2±23,8 and 135,6±37,3 IU/l respectively (II group). On the 52-nd week levels of transaminases essentially differed: ALT level at patients of the I group became 84,6±10,4, at patients of II group – 39,7±12,5 IU/l, AST – respectively 96,6±11,7 and 63,2±9,6 IU/l (p<0,01). The level of tumor necrosis factor-α significantly differed and was equal to 796,8±89,9 mcmol/l in patients receiving placebo, and 412,8±76,8 mcmol/l in group, receiving glycyrrhizinic acid (p><0,01). Conclusion. Application of phosphogliv along with abstinence increases efficacy of therapy of alcoholinduced liver disease. The further studying of this agent is necessary at various clinical variants of disease with dynamic evaluation of basic clinical and laboratory parameters and effects of treatment on liver morphology.>< 0,01). The level of tumor necrosis factor-α significantly differed and was equal to 796,8±89,9 mcmol/l in patients receiving placebo, and 412,8±76,8 mcmol/l in group, receiving glycyrrhizinic acid (p< 0,01).

Conclusion. Application of phosphogliv along with abstinence increases efficacy of therapy of alcoholinduced liver disease. The further studying of this agent is necessary at various clinical variants of disease with dynamic evaluation of basic clinical and laboratory parameters and effects of treatment on liver morphology.

The aim of review. To present diagnostic criteria of constipation of functional origin in children and to systematize approaches to medical programs development.

Original positions of the review. Functional constipation contributes 95% of all cases of constipation at children. According to ICD-10, in the respective section, irritable bowel syndrome (IBS) and functional constipation itself are traditionally distinguished. RomeIII criteria adjust diagnostic principles of these diseases. In pediatric practice it is important to distinguish hypertonic and hypotonic constipations. In medical programs significant place is given to laxatives, especially in cases of sub- or decompensated variants of constipation. Of them Forlax® preparation on the basis of macrogoal 4000 (polyethyleneglycol 4000) with potential of prescription of the latter from 6-month’s age deserves attention. In the literature there are data indicating safety and high performance of this pharmaceutical agent.

Conclusion. Rome criteria of IBS are applicable only in relation to children of middle and senior school age. At drawing up medical programs for children with functional constipation, it is advisable to take into account its type (spasmodic or hypotonic), degree of compensation, age of a child. At prescription of laxative agents it is necessary to choose drugs with osmotic mechanism of action.

Aim of investigation. To estimate frequency of flat adenomas of the large intestine in men and women of various age groups, that underwent total videocolonoscopy. To study macroscopic and morphological differences of flat adenomas in relation to locating within the large intestine.

Materials and methods. Total colonoscopy by CF-V70L device («Olympus», Japan) after preparation by Fortrans (macrogoal) «Ipsen» company (France) was carried out in 1859 patients, inhabitants of Kuzbass region. Each patient with suspicion to structural mucosal changes underwent guided chromoscopy with 0,2% indigo carmine solution. Neoplasms, which were revealed, were subjected to biopsy by FB-24U forcipes or resection by SD-17U loop («Olympus», Japan). Results. Overall 1859 patients were investigated, in 849 cases (45,7%) 1631 adenoma has been found, 1344 (82,5%) of them were of the I type. At 176 (9,5%) patients 287 (17,5%) adenomas II of type were revealed. Flat adenomas were found most often in males in the age of 30 to 49 years at the right part of the colon, 285 (99,3%) adenomas were of the IIa type, 270 (94,1%) were <10 mm in size. The majority of flat adenomas – 275 (95,8%) – had tubular structure, in 14 (4,9%) the high degree dysplasia was found. Conclusions. Flat adenomas of the large intestine – is not an infrequent disease among Kemerovo region inhabitants (it is found in 9,5 % of the patients undergoing total videocolonoscopy with chromoscopy). The risk of neoplastic transformation increases with increase of><10 mm in size. The majority of flat adenomas – 275 (95,8%) – had tubular structure, in 14 (4,9%) the high degree dysplasia was found.

Conclusions. Flat adenomas of the large intestine – is not an infrequent disease among Kemerovo region inhabitants (it is found in 9,5 % of the patients undergoing total videocolonoscopy with chromoscopy). The risk of neoplastic transformation increases with increase of the flat adenoma size, at the presence of central excavation and location in right part of the colon.

The aim of clinical case presentation. To represent the patient with chronic hepatitis C with severe hyperferritinemia and absence of dominant mutations of hereditary hemochromatosis gene.

Clinical case data. Patient К., 38 years, despite of rapid virologic response at combined antiviral therapy by pegilated interferon α-2а and ribavirin, had persistently high activity of transaminases and initially high level of serum ferritin increase twice.

Conclusion. Retrospective evaluation of developed clinical situation allows to assume, that ferritin in this case acted as acute-phase protein. On the other hand, taking into account high level of serum transaminases and lymphadenopathy (developed at the 20-th week of treatment), atypical side effect of the antiviral agents of idiosyncrasy type can be suspected. After cessation of the treatment course clinical and laboratory abnormalities reduced. Sustained virologic response was ascertained.

O.A.Maslova – Clinical and statistical investigation of stomach and duodenum peptic ulcer prevalence and treatment approach

S.A.Vorob’yev – Clinical and morphofunctional features of chronic gastritis associated with iron-deficient and В12-deficient anemia