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1.5. The general principles of antiviral therapy of chronic hepatitises at children and teenagers.

Inactive or maloaktivnyj, not differing progressing current HG, without signs replikatsii a virus does not demand medicamental treatment. Markers replikatsii viruses of a hepatitis in the presence of active chronic disease of a liver (the raised level of aminotransferases, histological signs of activity) and-or extrahepatic lesions are the indication for etiotropic antiviral therapy.

[73, 121, 289, 332]

3 basic groups of preparations are used: interferons, in, Y; analogues of nucleosides (ribavirin, lamivudin, famtsiklovir, adefovir, etc.) and immunostimuljatory (interlejkiny, Timosinum а-1, a vaccine against HBV). The basis of antiviral therapy HG is made by interferon (If). Experience
Clinical application rekombinantnyh IFN testifies that long interferonoterapija though promotes formation of antibodies to IFN at some patients, but not priv odjat neither to an organism allergization, nor to depression of medical effect. [73, 111, 178, 204, 279, 289, 332].

Rekombinantnye IFN. IFN possessing straight lines antiviral and immunomodulirujushchim action, is the important regulator of the local immune answer in a liver of patients with HGV. Really, appointment IFN promotes eliminatsii HBeAg and DNA HBV at chronic patients. There are bases to believe, that appointment IFN induces production of the endogenous cytokines playing the important role in eliminatsii HBV. Appointment depends on a condition of activity of T-cages. [327]

IFN, combining antiviral and immunostimulirujushchee the actions inherent to two other groups of preparations, possesses also antifibroticheskim action. Ability IFN to suppress an active fibrogenesis is accurately tracked by means of repeated biopsies of a liver and research of serumal level of a N-terminal propeptide of a procollagen of III type. It is noticed, that the estimation antifibroticheskogo actions IF can be carried out by means of maintenance research in blood serum N - a terminal propeptide of a procollagen of III type without application of invasive methods [4, 111, 177, 219, 247, 349].

Interferon an alpha-2a (Roferon) Possesses properties natural an alpha - of interferons of the person. It has antiviral an effect, inducing in cells a resistance condition to virus infections and modulating the response of the immune system referred on neutralisation of a virus or destruction of cells infected with them.

Interferon альфа-2Ь (Intron) renders antiviral, immunomodulirujushchee, antitumoral, antiproliferative action. Interferes with a virus becoming infected of cells, changes properties of a cellular membrane, prevents adhesion and penetration of a virus in a cell. Initiates synthesis of some specific enzymes, breaks synthesis of the virus
RNK and virus fibers in a cell. Stimulates process of presentation of an antigen to immunocompetent cells, modulates activity of the killers participating in antiviral immunity.

Interferon альфа-2Ь (Viferon) human rekombinantnyj possesses immunomodulirujushchimi, antiviral, antiproliferative properties. Immunomodulirujushchie properties of interferon, such as intensifying of phagocytic activity of macrophages, augmentation of specific cytotoxicity of lymphocytes to cells-targets cause its mediated antibacterial activity. At treatment Viferonom biochemical indicators within three or more months are normalised, the virusemia disappears, and Y-interferon level processes of fibrosing of a liver authentically raise, choke at chronic virus hepatitises at children.

[11, 111, 154, 219, 349]

At the present stage the basic preparations INF are pegilirovannye If. Joining to a molecule Of If large inert molecules polietilenglikolja has allowed to enlarge considerably its size and molecular mass and thus to slow down a clearance of a preparation from an organism, keeping its concentration in blood after an injection throughout a week. The preparation with higher activity which can be entered once a week, quite comparable with If on shipping is as a result received. At pegilirovanii ИФ-а-2а (Roferon) 40000 Dalton (Pegasis), ИФ-а-2Ь (Intron - with a molecule polietilenglikolja in mass 12000 Dalton (PegIntron) is bridged to a molecule polietilenglikolja in mass. Structure PEG immediately influences clinico-pharmacological characteristics of a preparation. In particular, the size and degree of bifurcation PEG defines indicators of an absorption, distribution and deducing INF [183, 170, 413, 279].

Main objective of antiviral therapy HG - reception of the proof answer providing normal level of aminotransferases and absence of serumal markers replikatsii of a virus, at least throughout 6 months after the treatment termination. Achievement of this purpose, as a rule, leads
Clinico-laboratory remission of disease, to positive dynamics of morphological changes with reduction of expression of a fibrosis of a liver (antifibrotichesky effect INF) also promotes stay or zayomedleniju illness advances, and also to depression of risk of development GTSK [219, 252, 259, 357, 349].

To the decision of a question on appointment of antiviral therapy should precede about the 6-month's period of observation with repeated biochemical both virologic researches and a liver biopsy. Last is necessary for an establishment of the exact diagnosis taking into account a degree of activity and a disease stage.

Indications for treatment INF.

Indications to carrying out PVT at children are possibility of full prevention of advance of illness under condition of achievement of the proof virologic answer (SVO), absence of the accompanying pathology interfering or complicating carrying out PVT, possibility of the careful parent control over adherence to treatment [416]. It is necessary to consider that circumstance, that children transfer PVT in comparison with adults [242, 282] is better. The economic party of question PVT has Great value: use at children's age of the antiviral preparations which are dosed out on mass of a body or on the area of a body, is characterised by economy of expenses in comparison with PVT at adults [111, 276, 279].

The direct indication to begin with PVT at children's age is presence at the child of a significant stage of a fibrosis (> 2 on METAVIR) [324, 332, 349].

Despite the fact of slow advance HG at children, it is necessary to consider “the missed possibilities” treatments when adult patients HG, have already "advanced" fibrosis, alcoholic or narcotic dependence, a metabolic syndrome with insulinorezistentnostju and not alcoholic steatogepatitom, a serious accompanying pathology [176, 279, 366, 436]. For this reason now among pediatrists the understanding necessity of the same wide approach for definition of indications to PVT prevails at
Children, as well as at adults, that is PVT it is shown all children having proved flowing HBV - a HCV-infection and not having contraindications for appointment of antiviral preparations [458].

To 3-year-old age PVT it is not spent. Taking into account features of development of children and teenagers, it is considered the most expedient carrying out PVT at the age of 5-7 years, that is prior to the beginning of training at the school demanding appreciable intellectual efforts from the child [41, 271, 332, 389]. The school period is bound not only to the raised intellectual load on a children's organism, but also crossed with pubertatnym the period when, followed try to avoid action of the preparations influencing physical development [427]. However, in any case, the decision of a question on expediency of carrying out PVT is exclusively individual in each concrete case of ascertaining HG both at the child, and at the teenager. Notice, that girls as a whole answer treatment, than boys is better. The ethnic parentage, initial level do not correlate the AlAT, the AsAT, initial level of DNA HBV with the answer to treatment [188, 315, 389].

Contraindications to PVT. If, possessing expressed immunostimulirujushchim effect, it should not be prescribed patient HVG with autoimmune disturbances; at extrahepatic lesions in which pathogenesis reactions GZT and autoimmune disturbances lay, and also at accompanying autoimmune diseases [369]. Contraindications to If also are accompanying serious illnesses, dekompensirovannyj a cirrhosis [86]. However in the literature there are data on successful antiviral therapy of patients with a cirrhosis [432].

Adverse prognostic factors. Those, from among concerning the virus characteristic, are: high level viremii, presence HBV - and HCV-mutants, 1 genotype HCV (especially lb). Adverse factors from the patient: the male, age is more senior 50 years, a long becoming infected, cirrhosis presence, low initial level of aminotransferases; the granules of iron taped at the morphological
Research of a tissue of a liver (high level of serumal iron and a ferritin), a cholestasia syndrome [86, 436].schitajut, that about 17 % of persons infected with a virus of a hepatitis With have at least one contraindication to therapy [436].

By-effects of antiviral preparations. Numerous collateral reactions are inherent to interferon. In the majority of works that collateral reactions to introduction of parenteral preparations rekombinantnogo IFN at children with HG is observed on different data from 20 to 83 % of cases is underlined, basically are weak or moderated though necessities to reduce a standard dose of a preparation in 1,5-2 times lead. About 5 % of patients refuse treatment in the course beginning, and 20 % do not finish it because of by-effects. By-effects dozozavisimy. It is most often defined grippopodobnyj a syndrome (a fever, a fever, delicacy, a headache, arthralgias, mialgii, a tachycardia). The diarrhoeia, loss of mass of a body, abaissement of hair, neurologic and mental disorder (depression), various autoimmune phenomena (more often others - a lesion of a thyroid gland to 11 %) [39, 86, 405] are observed dispepsicheskie the phenomena. As a result of antiproliferative and immunostimulirujushchego effects IFN the leukopenia and a thrombocytopenia develop, the anaemia is more rare. To rekombinantnym to types IFN neutralised antibodies are formed, again already come to norm against treatment level of aminotransferases thus can raise. Such phenomenon is more often observed at use ИФ-а-2а, unlike ИФ-а-2Ь. The attention the description caused IF draws of disturbances of a metabolism of lipids, first of all at patients with an initial lipidemia, especially with the raised level of triglycerides [174, 385, 405].

The hematological undesirable phenomena (the neutropenia, an anaemia) meet at 20,6 % of children, as a rule, are clinically not significant (not demanding corrections of a dose of preparations). On other data at children with HGS depression in blood of level of thrombocytes meets in 50,0 % and leucocytes in 40 % of cases, but are transitional and, as a rule, updating do not demand
Doses or cancellations of therapy [145,405]

The most known by-effect ribavirina is the good-quality hemolysis which is observed at 17-19 % of patients.

Possibility of its development demands carrying out of the clinical analysis of blood not less often than 1 time in 2 ned, especially in the first 2 mes treatment [5, 103, 238, 338, 405].

Against therapy INF often note depression of rates of growth of the child [441]. To undesirable effects of antiviral therapy HG possibility of development of autoimmune diseases is, the thyroid gland most often suffers. In исследованииMoiieston j.p.с co-authors (2013) underline, that occurrence of autoantibodies in the patients receiving PVT do not influence effect of therapy.

1.5.1.

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Scientific source Dmitriev Tatyana Gennadevna. CHRONIC VIRUS HEPATITISES At CHILDREN And TEENAGERS In REGION GIPERENDEMICHNOM. The PROGRAM of PERFECTION of RENDERING of the MEDIKO-SOCIAL HELP. The dissertation on competition of a scientific degree of the doctor of medical sciences. Yakutsk - 2014. 2014

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