VIRAL HEPATITIS

From Big Medical Encyclopedia

VIRAL HEPATITIS (hepatitis; grech, hepar, hepat [os] a liver + - itis) — the acute infectious disease with preferential defeat of reticuloendothelial system of a digestive tract, liver which is characterized by intoxication and often proceeding with jaundice.

Under the WHO recommendation, under the term «viral hepatitis» combine two diseases at which is essential epidemiol., wedge, and other distinctions (tab. 1): the hepatitis A which had more than 40 synonyms (an infectious disease, infectious hepatitis, epidemic hepatitis, catarral jaundice, etc.) and the hepatitis B which also had a large number of synonyms (serumal hepatitis, parenteral hepatitis, inoculation hepatitis, posttransfusion hepatitis, inoculative jaundice, spray jaundice, etc.).

Viral hepatitis of dogs (Rubart's disease), epizootic hepatitis of a cattle (fever of the valley the Rift), infectious anemia of horses make etiologically independent group. Damages of a liver at other nozol, forms of a virus etiology, napr, at yellow fever, are described in the relevant articles.

The historical sketch

Is described still by Hippocrates who pointed to an infectious form of jaundice. Numerous descriptions of a disease belong to medical officers in 18 and 19 centuries Frohlich in 1879 wrote about 34 epidemics of jaundice, calling it an army disease., Mass incidence after inoculations drew attention of doctors since 1885 when in Germany after vaccination against smallpox of, 191 people from 1289 vaccinated got sick century.

In 1883 S. P. Botkin came to the conclusion that catarral jaundice, to-ruyu before was considered for went. - kish. Qatar with a mechanical scholia, actually is only one of symptoms of the general disease. S. P. Botkin's lectures contain also instructions on a possibility of an anicteric course of hepatitis, on its interrelation with an acute yellow hepatatrophia. As S. P. Botkin the first assumed the infectious nature and allocated the first it in an independent nozol, a form, at the initiative of A. A. Kisel, this disease by right received the name «infectious disease» in our country.

In 1926 the Swede, doctors described epid, and assumed jaundice among patients of diabetic clinic that post-inoculation hepatitis is transmitted by the infected medical tools and differs from infectious hepatitis in a long incubation interval. Authors pointed also to possible existence of two various disease-producing factors [A. Flaum et al.].

Experimental justification of a virus etiology of a disease gave in 1937 Findlay and Mac-Kollum (G. Findlay, To. McCollum) in the analysis of outbreak of jaundice after immunization against yellow fever, and in 1938 Mac-Nalti and Propert (A. McNalty, Propert) — at vaccination against measles. Convincing data on the inoculation mechanism of transfer were obtained by P. G. Sergiyev and E. M. Tareev with coauthors (1940) during the studying of outbreak of jaundice in 1939 on the Black Sea coast after vaccination against fever of a pappatacha.

The largest epidemic of hepatitis B occurred in the USA in 1942 when all serviceman of army and fleet imparted a vaccine against yellow fever. From 2,5 million vaccinated 51 337 people after the incubation interval lasting from 40 to 120 days got sick. The donor serum included in vaccines served as the reason of infection.

The virus nature of hepatitis B was confirmed with researches on volunteers an amer. scientists Cameron (J. Cameron, 1943), Mack-Kollumom (1944), Hevensom (W. Havens, 1945), etc.

Geographical distribution

Is almost widespread everywhere, in all countries and on all continents. Incidence varies from sporadic cases to epidemics, and it is possible, and to pandemics, especially in military years.

It is considered that the first pandemic took place in 1915 — 1923. The second pandemic (1937 — 1945) was connected with World War II and extended to all countries of the world. In post-war years the third pandemic, edges arose and extends fades, again inflames.

According to WHO data (a series of technical reports 512, 1973), the frequency of detection of antigen of hepatitis B at almost healthy faces from Sowing. America and Western Europe makes 0 — 0,6% in comparison with 5 — 20% at persons from the countries Zap. Africa, Southeast Asia and Far East.

If to consider that detection of antigen demonstrates existence of an infection at the person, then the provided figures confirm considerable spread of hepatitis B among the population of all countries of the world. According to official figures, in 1972 in Canada 7344 diseases, in El Salvador — 3990, by Peru — 4592, Chile — 2458, Venezuela — 1853, Argentina (1971) — 8143 are registered. However the official data on incidence reported by WHO are submitted, apparently, underestimated. It can be explained with incomplete registration of patients. So, Gassner and the Coffin (M. of Gassner, P. Grob), providing statistical data on Switzerland, specify that only every tenth disease countrywide is registered.

Fig. 1. The chart characterizing incidence of a viral hepatitis on the republics of the USSR in 1974. Figures down — number of the diseased on 100 thousand population, across — the republics of the USSR: 1 — RSFSR; 2 — the Ukrainian SSR; 3 — the Belarusian SSR; 4 — the Uzbek SSR; 5 — the Kazakh SSR; 6 — the Georgian SSR; 7 — the Azerbaijani SSR; 8 — the Lithuanian SSR; 9 — the Moldavian SSR; Yu — the Latvian SSR; 11 — the Kyrgyz SSR; 12 — the Tajik SSR; 13 — the Armenian Soviet Socialist Republic; 14 — the Turkmen SSR; 15 — the Estonian SSR.

It is necessary to consider rather reliable and close to true data on a disease in the socialist countries. In 1971 in Romania 58 429 cases, in GDR — 19 935, Hungary — 9473, in 1972 in Poland — 84 729, Czechoslovakia — 17 162, Bulgaria — 14 895 cases are registered.

In the Soviet Union incidence also takes an important place (tab. 2). Incidence is higher in the republics of Central Asia (fig. 1).

An etiology

the Virus — the activator in pure growth is not allocated. Till 1967 was considered that only the person is susceptible to hepatitis A therefore the first message of F. Deinhardt and sotr. about reproduction of experimental hepatitis at the South American monkeys marmozt (Saguinus mystax) at infection with their blood serum of the patient it was met with mistrust. The subsequent researches confirmed a susceptibility marmozt also a possibility of transmission of infection on these animals by passages. Marmozet manages to infect not only with blood serum of the patient, but also a filtrate of excrements. Specificity of the allocated virus is proved by neutralization by its antibodies which are in serums of the people who had hepatitis A.

Two virus strains of hepatitis A differing in reaction to some physical are allocated. - chemical agents (MS and CR — 326).

Fig. 2. The diffraction pattern of the cleared virus of the hepatitis A (a strain of CR — 326) allocated from serum of monkeys marmozt (across Hilleman).

According to Hilleman (M. Hilleman) and sotr., the CR virus strain — 326 (fig. 2) contains RNA, is inactivated by ultraviolet rays and solution of formalin (1: 4000 within 3 days at t ° 37 °). Authors refer it to category of intestinal viruses.

Fig. 3. The diffraction pattern of a virus of the hepatitis A found in Calais the patient with method of an immune submicroscopy: and — particles (virions), free from antibodies; — the particles surrounded with antibodies (on Gravella).

Also the method of an immune submicroscopy for direct detection of a virus of hepatitis A (fig. 3) in excrements of patients [S. Feinstone with sotr is used.], which consists in connection of specially processed ultrafiltrate of excrements of patients with antibodies of serums of convalescents, sedimentation in the supercentrifuge, contrasting phosphatotungstic to - that and the subsequent viewing at high resolving power of a microscope. Gravell (S. of Gravelle) considers that the specified method yields clear results at a research of excrements of patients with hepatitis A and finds out virus-like particles of spherical shape of 27 nanometers in size that matches results of a research on marmozeta.

A. K. Shubladze and sotr. found a virus in leukocytes of blood of patients; at the same time revealed structural damages of chromosomes, suppression of mitotic activity and ability to a blasttransformation in cells. Authors managed to transfer a virus from leukocytes of patients to leukocytes of healthy donors of in vitro.

The virus etiology of hepatitis B also has strong evidences (filterability and infectivity of filtrates for the person). In studying of an etiology of hepatitis B opening was very important Australian antigen (see), described by Blamberg (V. S. Blumberg) in 1964 in the beginning as a squirrel, precipitant with antibodies of blood of the patient with hemophilia who received a repeated hemotransfusion and then as antigen which is regularly found in blood of patients with hepatitis B.

In spite of the fact that there is no consensus concerning identity of a virus and the Australian antigen, the last has indisputable diagnostic value and is used for differentiation of hepatitis A from hepatitis B.

In the USSR the first publications about the Australian antigen appeared in 1971 E. A. Paktoris and soavt. (1972) came to a conclusion that existence it is very specific and that it most often is found in the first days of a disease. In the next years definition of this antigen is used for diagnosis by many laboratories of our country. R. A. Kantorovich and soavt, confirmed earlier known facts about communication of antigen with hepatitis and reported about identification of antigen at children with a Down syndrome (30%) and with a smaller frequency at other hron, diseases (in particular, hemophilias). The Australian antigen is found also in donors (0,5%). It is possible to agree with E. A. Paktoris about specificity of the Australian antigen at hepatitis B, and existence it at other forms hron, pathologies it is probably connected with not recognizable hepatitis B or a carriage of virus.

The regularity of detection of the Australian antigen in blood of the patient and carriers assumes identity of a virus of hepatitis B with this antigen that finds confirmation in coincidence of high infectivity of serum of patients to concentration of antigen, existence it in kernels of cells of a liver at biopsies and autopsies, in immunity of people with a high level of antibodies to it at their infection with infectious serum of patients with hepatitis B.

Careful morfol, researches established preferential spherical shape of particles of the Australian antigen, 42 nanometers in size, with an outside fibrous casing and internal more dense core — a nucleocapsid.

The epidemiology

the Source of an infection at is only the person — the patient or a virus carrier.

At hepatitis A the greatest epid, danger is constituted by patients anicteric and subclinical (inaparantny, erased) forms of a disease as they make most of patients with hepatitis A.

At patients the virus contains in excrements, blood and urine. Hevens and Paul (W. Havens, J. Paul), S. Krugman and soavt, reported that the virus in excrements of patients most often is found in an incubation interval. The virus is allocated not only from contents of intestines, but also from blood, though with a smaller regularity.

Serious epid, also virus carriers matter. Children among whom the asymptomatic carriage (is most often observed see are the main source of a contagium. Carriage of contagiums ). The number of the not recognizable forms of hepatitis A proceeding without typical a wedge, symptoms and also virus carriers considerably exceeds number of clinically expressed forms of hepatitis.

Hepatitis A concerns to group of intestinal infectious diseases and is transmitted from sick (carrier) healthy through the waters infected with excrements, foodstuff and at direct contact. Also the role of flies in mechanical transfer of a virus is not excluded. The international group of experts of WHO considers that usually flashes, most often begin because of fecal pollution of water and food. However distribution usually happens in the contact way. Many water epidemics of hepatitis A are described. The largest of them was observed in India (Delhi) in 1951 when as a result of emergency penetration of sewer waters into a water supply system ached with hepatitis A more than 30 000 persons.

Some researchers consider that hepatitis A is transmitted also in the airborne way though experimentally it and is not confirmed. According to the International group of experts of WHO, droplet infection probably meets seldom. An opportunity at hepatitis A of transmission of infection is proved in the parenteral way (inoculations, injections with to lay down. purposes etc.). Incubation interval at the same time usual duration.

Age distribution of incidence is characteristic — children generally are ill. At emergence of epidemics age ratios can change considerably. The expressed seasonality is observed — incidence sharply increases during an autumn and winter season.

The persons who had hepatitis A remain susceptible to hepatitis B and vice versa.

As well as at hepatitis A, a source of a contagium at hepatitis B are the sick person and a virus carrier. The virus contains in blood of patients during all incubation interval and all acute period of a disease. Danger of transfer of hepatitis B is big owing to high pathogenicity of a virus. E.g., R. Murray considers that 10 - 6 the ml of plasma of a virus carrier is already enough for infection of the susceptible adult. These data are obtained as a result of direct infections of volunteers with ikterogenny plasma. In similar observations of J. Stokes and soavt, duration of a carriage of virus is established. Its limit experimentally established period — 5,5 years. On the same observations at the woman — a virus carrier, observed 3 years, at a biopsy of a liver it was not registered any clinical laboratory and morfol, aberrations. Given rise by it (by means of Cesarean section) and not kormlenny maternal milk the child at two-month age got sick with an acute hepatitis In (the confirmed infection of volunteers) and in 2 years died from hron, forms of a disease at the phenomena of fibrous regeneration of a liver. Similar observations, apparently, formed a basis for the hypothesis of an origin of hepatitis B offered F. Burnett who considers that the virus of hepatitis B is the option of a virus of hepatitis A which is transferred vnutriutrobno; at a fruit at further development and the birth either the disease is demonstrated, or the carriage connected with immunol, tolerance forms.

Transmission of infection at hepatitis B happens in the parenteral way. Infection can be as a result of use of badly sterilized tool (the syringe, needles, scarificators, a scalpel, etc.) at capture of blood, inoculations, hypodermic and intravenous administration of drugs, at various surgical manipulations etc. More often infection occurs at hemotransfusion or plasmas. After introduction to practice of gamma-globulin, and after a clumsy vaccine of a disease of hepatitis In the ambassador of protivokorevy prevention by blood serum of donors completely stopped.

The international group of experts of WHO (1973) stated judgment that it is impossible to explain only with one parenteral transfer an origin of all cases of hepatitis of V type. In literature there were messages that antigen of hepatitis B is found in saliva, urine, bile, Calais of patients and virus carriers. As reports to WHO (a series of technical reports 512, 1973), in the mosquitoes caught in some districts Zap. and Vost. Africa, the method of a counter immunoelectrophoresis found antigen of hepatitis B (respectively in 28 and 18 groups of mosquitoes of 12 types). However participation of blood-sicking arthropods in the mechanism of transfer of a contagium at hepatitis B can be found out only after their ability to transmit a virus at a sting is proved.

According to E. A. Paktoris (1972), not less than 50% of all diseases of adults belong to V G hepatitis serumal hepatitis occurs Among children less often and hl. obr. aged till 1 year.

Diseases of hepatitis B are not connected with any season and are registered during the whole year. Increase in incidence is quite often preceded by the mass immunization which is carried out by syringes of repeated use.

The pathological anatomy

acute Is studied by Patomorfologiya generally on material of puncture biopsies of a liver since lethal outcomes are rare (do not exceed, as a rule, 0,3%). Death comes from an acute or subacute massive necrosis of a liver more often, the patomorfologiya to-rogo is in details studied (see. Toxic dystrophy of a liver ).

The method of a biopsy allowed to establish a number of changes in a mucous membrane of intestines. Morfol, studying of all other systems and bodies at nonlethal forms of an acute hepatitis, especially in incubatory and in prodromal the periods, is practically not feasible.

Fig. 4. Microdrug of a liver at an acute viral hepatitis (puncture biopsy): also the inflammatory infiltrate in the central vein of a segment of a liver (is specified by shooters) getting into an adjacent parenchyma swelled; coloring hematoxylin-eosine; X300.
Fig. 5. Microdrug of a liver at an acute viral hepatitis (puncture biopsy): 1 — proliferation of star-shaped retikuloendoteliotsit (kupferovsky cells); 2 — a mitosis in star-shaped retikuloendoteliotsita; 3 — a coagulative necrosis of star-shaped retikuloendoteliotsit (Kaunsilmen's little body); 4 — a mitosis in a hepatocyte; 5 — a coagulative necrosis of a hepatocyte (Kaunsilmen's little body); in other hepatocytes initial phases of development of balloon (vacuolar) dystrophy; coloring hematoxylin-eosine; X760.

At acute morfol, changes in a prodromal stage arise for 1 — 7 days before emergence of the first a wedge, symptoms of a disease and begin with activation and reproduction of star-shaped retikuloendoteliotsit (kupferovsky cells), and also an endothelium of terminal hepatic collectors, in a zone of transition of the sinusoidny site of capillaries of an acinus to postsinusoidny — venous. Around terminal hepatic collectors — perivascular infiltration from polymorphic mononuclear cells (fig. 4). In portal paths hypostasis and plentiful infiltration by the mononuclear cells reminding atypical lymphoid cells or reticular histiocytes with small impurity of plasmocytes develops. There is a diffusion proliferative reaction of kupferovsky cells with formation of free cellular forms. A part of kupferovsky cells is exposed to coagulative to a necrosis (see). At the end of a prodromal stage changes of hepatocytes join: anizonukleoz with increase in the sizes of kernels and dominance of large kernels, numerous, hl. obr. patol., mitoses in various zones of a parenchyma, scattered proteinaceous dystrophic changes, it is preferential in hepatocytes of a peripheral zone of an acinus (the third zone of an acinus).

By the beginning of clinical — the icteric period of a disease there is already expressed patomorfol, a picture. Vacuolar (balloon) dystrophy and necroses of hepatocytes with formation of the eosinophilic little bodies similar to Kaunsilmen's (fig. 5) little bodies joins earlier arisen changes.

Fig. 6. Microdrug of a liver at an acute viral hepatitis (puncture biopsy): the progressing development of diffusion acute balloon dystrophy of hepatocytes (1); diffusion proliferation of star-shaped retikuloendoteliotsit (2), a mitosis in a hepatocyte (3); coloring hematoxylin-eosine; x 760.
Fig. 7. Microdrug of a liver pr acute viral hepatitis (puncture biopsy): the center of devastation of a parenchyma on site a necrosis in a zone of peripheric circulation of an acinus (it is specified by shooters) with inflammatory infiltrate from polymorphonuclear leukocytes and lymphoid elements; coloring hematoxylin-eosine; X 300.

During the maximum changes (2 — the 5th week of a disease) proliferative reaction of a mesenchyma prevails in the beginning. Inflammatory infiltrates of portal paths merge with infiltrates of a parenchyma; in them the quantity of plasmocytes increases, eosinophilic and single neutrophilic leukocytes appear. Balloon dystrophy (fig. 6) and a necrobiosis of hepatocytes, and also changes of walls of vessels accrue that along with diffusion cellular infiltration breaks structure of a hepatic parenchyma. Considerable proliferation of the bilious courses with development of fields of «oval» cells and false bilious channels is noted. Expressiveness of changes in various acinus is not identical. Changes of hepatocytes within the same acinus are various owing to asynchrony of their emergence and various forms of proteinaceous dystrophy. In more hard cases the quantity and the size of the centers of a necrosis, hl increases. obr. in zones of the periphery of an acinus, up to formation of submassive and massive necroses. By the end of the period of the maximum changes the quantity of mitoses of hepatocytes decreases, the quantity of an amitoticheska of the sharing cells, in bilious capillaries — quantity of bilious blood clots increases; the reticulin stroma of a parenchyma coarsens, is partially collagenized, especially in the field of terminal hepatic collectors and on the periphery of axial sinusoid. In the centers of a necrosis there are sites of devastation of a parenchyma (fig. 7), larger in peripheral departments of an acinus; these sites contain fragments of hepatocytes, after eliminiruyemy blood or partially englobed on site in the beginning. In the small centers of a necrosis there are accumulations of lymphocytes and large macrophages — the necrophages containing fragments of cells and a brown-yellow pigment — so-called late small knots. The reticulin stroma in the centers of a necrosis, especially in the third zones of an acinus, is fallen down.

Fig. 8. Microdrug of a liver at an acute viral hepatitis (puncture biopsy): involution of dystrophic changes of hepatocytes; formation of «late» small knots (it is specified by an arrow) with the remained coagulative necrosis of hepatocytes (a) and without coagulative necrosis of hepatocytes; coloring hematoxylin-eosine; x 760.
Fig. 9. Microdrug of a liver at an anicteric form of an acute viral hepatitis (puncture biopsy): plentiful infiltrates (are specified by shooters) in the central vein of a segment of a liver (the upper drawing) and in the field of a portal path (the lower drawing); coloring hematoxylin-eosine; X 300.

In the period of involution and reconvalescence (the 6th week of a disease) cellular infiltration, dystrophic changes and polymorphism of hepatocytes gradually decreases and disappears, sites of devastation of a parenchyma come to light more accurately. By the end of the period remain only small lymphocytic fibrotsitarnye the infiltrates which are limited to portal paths and «late» small knots (fig. 8) which considerably decreased in sizes and quantity. Patol, process usually completely comes to the end on 7 — 8th week of a disease. Long time insignificant infiltrates in portal paths — the central vein of a segment of a liver (fig. 9) and the remains of «late» small knots, focal accumulations of the macrophages loaded with a brown-yellow pigment, hl can remain. obr. in the third zones of an acinus, insignificant polymorphism of hepatocytes about a nek-eye surplus of two-nuclear cells.

Each of listed morfol. signs it is separately not specific for acute and meets at many other damages of a liver. However all complex of changes and their typical dynamics are characteristic for. The picture of changes, close to these, is observed at so-called gepatitopodobny forms of toksiko-allergic medicinal hepatitises, differential morfol which diagnosis is quite often difficult.

Electronic and microscopic and gistokhy, researches do not reveal specific to changes. Showed Gistokhim, a research that in the majority of cells synthetic activity of a kernel and kernel in the form of strengthening of reaction to RNA and proteins amplifies. In cytoplasm of hepatocytes ratios between keeping of separate functionally active groups of proteinaceous molecules change that reflects disturbances of synthesis and metabolism of proteins; activity of a number of enzymes decreases.

Change of activity of enzymes in tissue of a liver is not specific for and testifies only to character and extent of dystrophic changes of hepatocytes. In the cells which are exposed to «enlightenment» and balloon dystrophy, the granular Endoplasmic reticulum gradually is fragmented, collapses; content of proteins in cytoplasm decreases, the glycogen disappears, swelling and disintegration of mitochondrions develops. In the cells which are exposed to a coagulative necrosis there is a condensation of structures and strengthening gistokhy, reactions to the proteins caused by dehydrational processes in cytoplasm and a kernel. At formation of eosinophilic little bodies the coagulative necrosis takes quite often all cell, at partial necroses — the fragments of cytoplasm, various in size and a set of organellas, further forming with participation of lysosomes autofagichesky and the sequestered vacuoles. At electronic microscopic examination in kernels and cytoplasm of hepatocytes and kupferovsky cells at hepatitis B virus-like particles are found. At the same time antigen, and in kupferovsky cells as well cell-bound immune complexes is defined by immunofluorescent and immunielectron and microscopic methods.

Features morfol, changes of a liver allow to distinguish the following main forms.

At an anicteric form morfol, changes of a liver are characterized by the expressed proliferative reaction of kupferovsky cells and connecting fabric of portal paths at the insignificant or almost absent changes of a parenchyma.

The long acute hepatitis morphologically differs in considerable prolixity (sometimes up to several months) dynamics of changes, especially the periods of the maximum changes and reconvalescence.

The persistent acute hepatitis differs in duration of an active phase (sometimes till 1 year) without any tendency both to a usual cyclic current, and to transition in hron, hepatitis. It is characteristic that throughout all disease it is possible to observe at the same time all stages of a usual cycle of changes.

At a recurrent acute hepatitis against the background of all morfol, the changes typical for a cyclic form, the changes characteristic of its initial phase appear again.

Morfol, distinction of cholestatic and holangiolitichesky hepatitis in some cases is difficult as both the cholestasia, and defeats of the bilious courses make an indispensable component of a usual cyclic form of a disease. Cholestatic forms, obviously, should be considered at which the intra hepatic cholestasia is expressed especially brightly, reaching sometimes degree of a considerable extrahepatic cholestasia.

In the outcome there can come the full anatomic restitution of tissue of liver. At heavier development of process and in case of a long current fibrosis can develop and cirrhosis (see) which usually has character of postnecrotic.

The pathogeny

the Pathogeny is insufficiently studied. However at comparative analysis a wedge, manifestations of various forms of disease at the person, biochemical, researches, patomorfol, and immunomorfol. data, gl.obr. biopsy material, taking into account results of observations on a current at various animals, it is possible to accept the general scheme of a pathogeny stated in G. P. Rudnev (1966) works, V. M. Zhdanova and soavt. (1968), I. F. Barinsky (1968), B. K. Bezprozvanny (1969), A. F. Blyugera (1969), etc. According to this scheme in the first phase of infection the activator gets into an organism in various ways: at hepatitis of A type — preferential enteral way, at hepatitis B — parenterally. In an incubation interval from the moment of infection before development a wedge, displays of a disease patol, process takes place a number of the consecutive interconnected stages: at first the leading role belongs to reactions of direct interaction between a virus and a macroorganism, then in the presence of conditions for reproduction the activator is reproduced in fabrics regional limf, nodes; after its accumulation primary follows virusemia (see). However sufficient information about the place of primary reproduction of a virus in an organism is absent. Only based on indirect morfol, signs, it is possible to believe that at hepatitis A it begins in intestines, in its regional limf, nodes. Then generalized defeat of reticuloendothelial system and a secondary reproduction of a virus in it follows that aggravates damage of cells of this system with formation of the «virus — a cell» complex not inherent to a healthy organism. Further defeat by a virus of hepatic cells with their reorganization on synthesis of virus proteins leads to emergence of the autoimmune reaction against hepatic cells playing an important role in progressing of process. Patol, process develops as reaction of hypersensitivity of the slowed-down type with dominance of cellular autoimmune reactions (along with specific antiviral reactions). The accruing receipt of a virus from regional limf, nodes in the general blood flow exceeding so-called threshold size causes maintenance and further development of infectious process. In the period the wedge, displays of a disease, since the preicteric period, generalization of the activator results selective defeat of a number of bodies and systems of an organism. A picture damage of a liver is further defining a wedge. Immunofluorescent and elektronnomikroskopichesky researches confirmed presence of the virus agent in tissue of a liver. Works of the 70th of 20 century also demonstrate that in cells of a liver the Australian antigen is found. So, S. Furuta and soavt. (1975) method of a direct immunofluorescence of biopsy material of a liver revealed 2 types of localization of the Australian antigen: in cytoplasm and on the surface of a hepatocyte. At the carriers of this agent which do not have symptoms of hepatitis and with insignificant gistol. changes, the Australian antigen (see) it was found on a cellular membrane. At the faces sore with cirrhosis, hron, hepatitis and primary gepatomy, the Australian antigen was localized in cytoplasm of cells. Extent of defeat of cells of a liver depends not only on disease, degree of a reproduction of a virus in an organism, but also considerably on specific features of the patient, on a condition of tension of nonspecific and specific immunity, and weight a wedge, diseases — on extent of disturbance of proteins of hepatic cells and their synthesis. Possibly, this process is connected not so much with direct action of a virus how many is a consequence of virus defeat of cells. Thus, actually acute infectious process can be counted up only the first stages of its development to generalized defeat of reticuloendothelial system. Wedge, the period of a disease, i.e. hepatitis literally, is not an onset of the illness, but hl. obr. consequence of primary infectious process.

Infectious process can break at any stage. If it terminates on early phases, then the disease proceeds subclinically, is erased or is abortal. To the contrary, process can linger on certain stages that involves development long and hron, forms, or to proceed with resuming of waves of generalization and palindromias. At the same time hypersensitivity reactions of cellular and humoral type which frequency by 5 — 10 times exceeds frequency external a wedge, displays of an allergy and paraallergy at this disease naturally develop.

Immunity

the Problem of immunity, as well as a pathogeny, especially at hepatitis B, remains not resolved. Consider that at hepatitis B there is a postinfectious immunity of weak tension. Possibly, it is explained by deficiency of antigen or its weak adaptation to biol, to environments of an organism. If the Australian antigen is quite often found in patients with hepatitis B in blood serum, then antibodies to it meet very seldom. Apparently, at this hepatitis specific immunity has cellular character (E. M. Tareev and soavt., 1975).

Assume that at hepatitis A newborns receive antibodies from the had mothers owing to what immunity remains at them till 1 year. Adults, having had hepatitis A at children's age, gain the postinfectious immunity of specific character remaining it is long, even for life. Thus, immunity at has strictly standard character, i.e. immunity against hepatitis A does not protect from a disease of hepatitis B and vice versa. In addition to specific immunity, an essential role during and outcomes at have also nonspecific factors (interferon, a lysozyme, a complement, etc.).

The clinical picture

the Acute hepatitis

the Acute hepatitis proceeds cyclically. In its current distinguish four periods: 1) incubatory; 2) prodromal, or preicteric; 3) icteric, or period of a heat of a disease; 4) reconvalescences. There are no fundamental differences in a wedge, the course of hepatitis A and hepatitis B, however big weight of a current and outcomes is inherent to the last.

Duration of an incubation interval at hepatitis A makes from 3 to 6 weeks, at hepatitis B — from 9 to 26 weeks and more.

The prodromal stage lasts 1 — 2 week, is absent only in 0,8 — 5% of cases. It is more often shown by a dispeptic syndrome and fever, is more rare pains in the right half of a stomach. The catarral phenomena, an artralgichesky or rhematoid syndrome, various allergic reactions, hemorrhages can be observed. As a rule, are expressed astheno - the vegetative phenomena. In blood — an insignificant leukopenia, band shift, a moderate eosinophilia, a relative lymphocytosis. The giperfermentemiya (fermenturiya) — increase in activity of alaninaminotranspherase, and also a number of organospetsifichesky enzymes is natural. By the end of a prodromal stage the hyperbilirubinemia at the expense of direct fraction, an urobilinuria is noted, sedimentary tests change.

Duration of the icteric period usually does not exceed 1 month. It is characterized by quickly accruing jaundice (see) pechenochnokletochny origin, release of the dark brown urine containing bilious pigments, decolouration of excrements, a skin itch, increase and morbidity of a liver, and it is frequent also spleens, a lymphadenopathy, bradycardia and arterial hypotension, the phenomena of «an acute infectious kidney». Excretory and intra secretory functions of a pancreas are broken. Secretory and motive frustration are noted went. - kish. a path, disturbance of a nervous system in the form of apathy, depression, bad mood, easy irritability, euphoria, at severe forms — in the form of drowsiness or psychomotor excitement, endocrinopathies. In blood — eritro-and a macrocytosis, a leukopenia with a relative and absolute neutropenia, an eosinophilia, a monocytosis and a lymphocytosis, retikulo-plazmotsitarny reaction of marrow, moderate

thrombocytopenia; ROE is slowed usually down. The central place is taken biochemical, by the shifts caused by functional disturbances of a liver: disturbance of pigmental exchange — hyperbilirubinemia (see), hl. obr. due to increase in direct fraction with increase (according to weight of a disease) a bilirubinovy indicator; a bilirubinurea, decrease in concentration of stercobilin in Calais. Disturbances of synthetic and complexing function of a liver — a hypoproteinemia, moderate decrease in abundance of albumine, passing increase in fractions alfa2-and partly gamma-globulins with change albumino - gamma globulinovogo and albumino-globulinovy coefficients, falloff of alpha lipoproteids with increase in coefficient betas lipoproteids / alfa-lipoproteidy are expressed. Positive reaction on Paraproteina and change of sedimentary tests, decrease in maintenance of a prothrombin, fibrinogen, change in all phases of a blood coagulation are observed; disturbances of fermental balance — increase in activity of such pechenochnokletochny isoenzymes as zymohexase, aminotransferases in a liver, blood, urine and other bodies and fabrics, and also change of activity of organospetsifichesky enzymes and their isoenzymes with disturbance of subcellular localization. Bonds of apoenzymes with coenzymes are damaged; changes of interstitial exchange — quantitative and high-quality shifts of amino-acid composition of blood serum and tissue of a liver, disturbance of mochevinoobrazovatelny function of a liver are noted; carbohydrate metabolism — a spontaneous fruktozuriya, changes of anaerobic glycolysis and glyconeogenesis is broken; lipidic exchange — decrease in content of cholesterol, generally at the expense of its ethers, with reduction of an indicator of esterification, increase in content of bile acids changes; the maintenance of microelements changes.

Involution of symptoms — recovery of appetite, easing of jaundice, a polyuria, reduction of the sizes of a liver, involution of functional shifts is peculiar to the period of reconvalescence. Duration of the period usually 7 — 15 days, but can reach 2 — 3 and more months.

On the course of a disease and expressiveness of the leading symptoms — degree of intoxication, intensity of jaundice and a hepatomegalia — in acute can allocate easy, medium-weight and severe forms with inclusion in the last group of patients with massive and submassive necroses of a liver, i.e. an acute and subacute hepatatrophia, or a malignant current.

With jaundice proceed approximately equally often in the easy and medium-weight forms making 85 — 95% of all cases, and only 5 — 10% fall to the share of severe forms.

The easy current is characterized by poorly expressed intoxication, slight jaundice (content of bilirubin in blood no more than 5 mg of %, on Endrashika), small increase in a liver, spleens, moderate shifts of sedimentary tests (sublimate to 1,5 ml, timolovy to 8 units are more rare at norm of 1 — 4 unit). Activity of zymohexase does not exceed 20 — 25 units, aminotransferases — 300 — 400 units, activity of cholinesterase, an arginase, an urokinase and other enzymes remains within norm. Content of crude protein of blood changes a little, to 2 — the moderate shift aside a hypergammaglobulinemia concentration of cholesterol within norm is noted 3rd week of a disease or it is slightly reduced, the coefficient betas lipoproteids / alfa-lipoproteidy is moderately increased. Laparoscopic find the liver increased brownish-red color with a «mirror» surface that is explained by its hyperemia, hypostasis and a lymphostasis. The condition of the patient quickly improves, the sizes and functions of a liver are normalized, the general duration of jaundice does not exceed 2 — 3 weeks; the average duration of stay of the patient on a bed — 22 days.

Intoxication is inherent to a medium-weight form, edges it is shown by lack of appetite, nausea (sometimes vomiting), a headache, considerable more expressed jaundice (a bilirubinemia of 5 — 10 mg of %) and a hepatomegalia, a splenomegaly; is followed by a skin itch, language is laid over, dry; the stomach is blown up, there is a lock, ponosa are more rare; abdominal pains are noted. There can be nasal bleedings. As a rule, bradycardia and hypotension are observed. Changes of functional trials of a liver are expressed more considerably: sublimate test of 1,5 — 1,3 ml, timolovy 8 — 10 units, activity of zymohexase of 30 — 35 units, aminotransferases of 400 — 500 pieces. Sharply activity of organospetsifichesky enzymes, indicators of a nitrogen metabolism change. The amount of albumine is considerably reduced, the content of alfa2-globulins is increased, contents beta is changed and gamma-globulins, are found Paraproteina. At a laparoscopy — «a big red liver» with the expressed hypostasis and a lymphostasis of the capsule, gentle visceroparietal commissures, roundish edge; a gall bladder pale, edematous, fallen down; on the surface of a liver places punctulate hemorrhages and cracks of retractions in sites of necroses. The change during a disease begins with diuretic crisis, there is an appetite, the dream improves. Duration of all shifts considerably big, than at an easy form, napr, duration of jaundice apprx. 30 days. Average duration of stay of the patient in a hospital of 28 days; the general duration of a disease is 6 — 8 weeks.

The main sign and criterion of weight at a severe form — defeat of c. N of page: in one cases sick eyforichna, do not realize weight of the state and do not show complaints, in others — are sleepy, sluggish, the rhythm of a dream is broken, dizzinesses, headaches are noted. The preicteric period usually happens rough, with high, fever, anorexia, nausea, vomiting which amplify during the icteric period of a disease. The symptomatology of the icteric period is sharply expressed: jaundice of a saffron shade (level of bilirubin reaches 15 — 20 — 40 mg of %), the bleeding ulitis and other hemorrhagic manifestations (nasal, uterine bleedings and so forth); language is laid densely over, dry; the liver has the small sizes or quickly decreases, a consistence its pasty. The spleen is, as a rule, not increased. The persistent bradycardia which during the progressing of a disease is replaced by tachycardia. The considerable giperfermentemiya — activity of aminotransferase more than 600 units, zymohexases — more than 35 units, the expressed decrease in content of albumine, high content alfa2-and gamma-globulins, beta lipoproteids, paraproteins, low level of cholesterol (90 — 50 mg of %), a prothrombin (40 — 50%), decrease in indicators of sublimate test to 1,2 — 0,7 ml is noted. Laparoscopic find the same picture, as at moderately severe, but more motley because of a sharp hyperemia, big sites of a necrosis, hypostasis, a large number of hemorrhages and a significant amount of cracks of retraction.

The termination of vomiting, nausea, emergence of appetite, recovery of a dream, disappearance of headaches, normalization of pulse and the ABP, diuretic crisis — the first harbingers of stabilization patol, process; after this its involution begins. Recovery occurs usually on 9 — 10th week of a disease. However approximately in 4 — 10% of cases severe forms can end with an acute massive necrosis of a liver and development of malignant option of a disease. Late hospitalization or premature extract from a hospital, heavy physical are considered as the adverse factors burdening disease. work, an alcohol abuse in a preicteric stage of a disease, the serious mental experiences postponed shortly before, exhausting and allergizing an organism of a disease, alimentary insufficiency, medicinal intolerance, accession of consecutive infection, operative measures which are especially made according to wrong indications, pregnancy last months. An undoubted role is played by an age factor: the lethality from with a massive or submassive necrosis of a liver is much higher among children (especially chest age) and at advanced age.

Among the signs giving the grounds for perhaps earlier recognition of a malignant current it is possible to point to the expressed psychological frustration (depression or excitement, drowsiness or sleeplessness, slackness, a fastidium, an adynamia) which are combined usually with intensively accruing jaundice, considerable feverish reaction, a pain syndrome, the tachycardia, bent to bleedings, development of ascites and hypostases expressed by morbidity and the progressing reduction in the sizes of a liver, considerable disturbances from other bodies (a myocardium, kidneys, etc.). From laboratory indicators it should be noted a leukocytosis, the accelerated ROE, the low maintenance of thrombocytes, deep shifts of all main functions of the liver — deaminizing anti-toxic, exchange of bilirubin, carbohydrate, protein metabolism, electrolytic balance, etc. One of essential symptoms is falling of activity of pechenochnokletochny enzymes at increase in content of bilirubin in blood, i.e. bilirubino-fermental dissociation, and also falloff of a prothrombin in go an index. At a malignant form development prekomatozny and coma Is possible (see. Coma ); in large part cases the hepatatrophia with a lethal outcome develops (see the Liver), however recovery of certain patients with complete regeneration of a liver or a wedge, treatment with formation of a «cicatricial» liver is possible. Point also to more frequent development at these forms hron, hepatitis and postnecrotic cirrhosis, and also acute cirrhosis (see. Cirrhoses of a liver ).

The anicteric form differs from icteric in smaller expressiveness a wedge, symptoms and lack of a syndrome of a hyperbilirubinemia with a simultaneous enzimol. shift and partial disturbance of pigmental exchange (darkening of urine, especially at the end of a prodromal stage, short-term decolouration of excrements), however defeat of hepatic cells quite often is considerable. Frequency of anicteric forms fluctuates over a wide range; the same number of anicteric forms are the share of each patient with jaundice.

Subclinical (latent, or inapparantny) a form — the reduced form of a disease, at a cut structurally functional changes are not followed a wedge, manifestations, but are naturally shown by enzymatic and are more rare shifts of other datas of laboratory. Usually comes to light among the persons which were in contact with the diseased with an icteric form; the hl is defined on the basis of laboratory, and. obr. enzimol. tests.

The anicteric, subclinical, latent forms are had huge epidemiol, value and at the same time on the frequency of possible failures significantly do not differ from icteric forms.

Acute the long current does not keep within in usual for a cyclic form (1 — 2 month) terms, and 3 — 8 months and more proceed. Among the reasons promoting a long current matter late hospitalization, mental and physical. injuries, associated diseases (hron, diseases went. - kish. path and bilious ways, diabetes mellitus, tuberculosis, alcoholism, etc.), advanced age of patients.

At cholestatic (holangiolitichesky) into the forefront in a wedge, a picture of a disease the symptomatology of mechanical jaundice (intra hepatic obturation) acts that creates considerable difficulties in an otgranicheniya of a similar form from extrahepatic jaundice. It is observed more often at women. Klien, symptomatology is in detail described by Watson and Hoffbauer (S. Watson, F. Hoffbauer, 1946). Of a preicteric stage it is characteristic a wedge, a triad — fever, arthralgias, urtikarny rash. The defining sign is intensive and long (2 — 4 months) jaundice with the weak painted or completely decoloured chair, negative reaction in urine to urobilinigen, a persistent skin itch from the first days of a disease at satisfactory health of the patient, with insignificant increase in a liver, frequent emergence at height of a disease of a symptom of Courvoisier (in connection with regional lymphadenitis, a serous inflammation and hypostasis of a wall of a gall bladder), acceleration of ROE, increase in content in blood of an alkaline phosphatase, cholesterol, phospholipids, a peculiar greenish color of a surface of a liver according to a laparoscopic research. Differs in the favorable forecast, development of biliary cirrhosis is in rare instances possible.

Long preservation of activity of infectious process without tendency to involution for several months is inherent in persistent hepatitis.

At morfol, and a laparoscopic research at patients the picture «big red» or «big white» a liver, inherent to an acute phase is noted. It is in detail described by Smetana (N. Smetana, 1957). Meets seldom. In a clinical picture «the belly discomfort», the dispeptic phenomena, a pain syndrome dominate. The liver is increased and condensed, functional trials throughout a disease are considerably changed. Always comes to an end with an absolute recovery.

Aggravations and a recurrence, relatives on the genesis, are observed in the first 2 — 4 months approximately in half of cases after the termination of hospitalization. They can be connected with physical. or a nerve strain, the early termination of a bed rest and treatment, disturbance of a diet or an intercurrent infection, and also using during sanatorium treatment of contraindicated mud procedures and bathtubs. Cancellation of hormones at treatment of patients with corticosteroids can be the cause of a recurrent current (a so-called steroid recurrence).

Harbingers of a recurrence are deterioration in overall health, temperature increase and emergence of a pain syndrome, increase of activity of serumal enzymes (especially cholinesterases and arginases). Clinically a recurrence is shown by the same symptoms, as the previous acute period of a disease, however their current is easier and less long. In some cases only the isolated waves of a giperfermentemiya — a so-called biochemical recurrence are observed.

The residual phenomena can remain for several weeks and even months in the form of complaints of patients astheno - vegetative character, the painful and dispeptic phenomena. In these cases the subikterichnost of scleras, a mucous membrane of the sky (less often) of integuments with the corresponding disturbances of pigmental function of a liver (increase indirect or, more rare, direct fraction of bilirubin in blood, patol, an urobilinuria), moderate increase in a liver, change of its functional trials (a hyperproteinemia, a hypergammaglobulinemia, positive sublimate and timolovy tests, Veltmann's reaction) are possible. Disturbances of excretory function of a liver and microcirculation and, at last, morphological features of the postponed acute process — traces of the centers of desolation of a parenchyma with availability of fine connective tissue fibers and focal collagenization of walls of sinusoid, accumulations of a bilious pigment, lipofuscin or a ferriferous pigment in macrophages, insignificant are noted (hl. obr. fibrotsitarny) infiltrates in portal paths and periportal areas, residual dystrophic changes of hepatic cells in the form of light swelling, an adiposity with simultaneous reduction of stocks of a glycogen. As a rule, «morphological healing» takes 12 — 16 weeks, and in some cases comes in much later terms.

The pain syndrome arising through various terms after postponed, is characterized by constant or pristupoobrazny pains in right hypochondrium with irradiation in a back (it is frequent at the combined damage of a pancreas), amplifying after meal or physical. tension, overfatigue, experiences. This syndrome usually is not followed by development of jaundice, the dispeptic phenomena, temperature increase, changes of functional trials of a liver, a hepatomegalia. Such state more than in 2/z cases is caused by dyskinesia of bilious ways. At such patients changes from a nervous system are, as a rule, noted — irritability, hypererethism, a sleep disorder, a headache. Diskinetichesky frustration happen usually rather resistant. Perhaps also developing of cholecystitis and the cholangitis caused by a secondary bacterial flora or the most viral infection and which are characterized by subfebrile condition, existence of inflammatory elements in the draft of bile, changes of peripheral blood. Laparoscopic — a picture of a perihepatitis and a pericholecystitis.

Approximately at 1/3 convalescents the combination of the dispeptic phenomena to emaciation, the pains in epigastriums irradiating to the left is observed. Disturbances externally - and intra secretory function of a pancreas, decrease in maintenance of a lipase and amylase in duodenal contents are possible. Quite often there are disturbances of gastric secretion with its oppression due to disorder of nervnoreflektorny regulation of secretion.

Astheno - the dispeptic syndrome is characterized by a combination painful, dispeptic and astheno - the vegetative phenomena without laboratory and morfol, signs of damage of a liver. The term is offered by Walsh and Sherlock (Y. Walshe, S. Sherlock, 1946) after the detailed description of a syndrome Benjamin and Hoyt (J. Benjamin, R. Hoyt, 1945). Complaints of asthenic character prevail: increased fatigue, the suppressed mood, sleeplessness, weakness, irritability, feeling of alarm, a tremor. Can be observed hypochiondrial or a depression, disturbances of a libido, impotence. Patients have no appetite, they grow thin; the intolerance of greasy food, nausea, feeling of completeness or pressure in a stomach or the right hypochondrium amplifying at long stay in a sitting position, during the walking, standing, driving in the car are noted. The only objective sign of this syndrome is a nek-swarm consolidation and increase in a liver. In an origin of a syndrome the great value is attached to psychoneurotic shifts. Big frequency of its development in persons of brainwork is emphasized. The symptomatology can last from several months to several years, no more than a year is more often.

Periodic increase in blood of bilirubin, in some cases with visible slight jaundice for several days is peculiar to the Postgepatitny hyperbilirubinemia, is more rare than weeks at a normal anatomic and functional condition of a liver. Meets more often at men. Content of bilirubin in blood serum in most cases exceeds 1 mg of % (on average 2 — 3 mg of %), generally at the expense of indirect fraction. The bilirubinurea is absent. Emergence of jaundice is preceded, as a rule, by physical. or mental loading, intercurrent infections, disturbance of a diet. During increase in bilirubin the passing hepatomegalia, sometimes a splenomegaly can be noted. By laboratory and tool methods disturbance of poglotitelnoekskretorny function of a liver comes to light. Signs of an increased hemolysis of erythrocytes, high content of hemoglobin can be observed. Morphologically against the background of almost usual very tectonics of a liver accumulation of the small, powdered golden-brown pigment, at electronic microscopic examination representing elements of bile and, more rare, granules of lipofuscin, with preferential localization near biliary poles of hepatocytes, increase of number of «glikogenovy» kernels and a hyperplasia of agranular profiles of an endoplasmic reticulum, change of a sinusoidal pole of hepatocytes, various stages and forms of obesity of hepatic cells is noted. A postgepatitny hyperbilirubinemia first of all damage of functions of capture and conjugation of bilirubin in connection with a lack of transferase glucuronic to - you, and also disturbance of other links of exchange of bilirubin, and first of all is the cornerstone of excretion of a bilious pigment. In a pathogeny of an insignificant part of postgepatitny hyperbilirubinemias increase in hemolysis and a catabolic form of formation of shuntovy bilirubin has major importance that gives the grounds to rank them as hemolitic jaundices from which they differ in normal life expectancy of the circulating erythrocytes. Duration of a disease usually more than 6 months, a current favorable, without bent to progressing.

The Postgepatitny hepatomegalia — the isolated increase in a liver found in convalescents 1 — 2 years later; the wedge, manifestations, dysfunction and very tectonics of a liver are absent. This state is most often caused by residual fibrosis of portal fields and, partially, periportal sites of fabric of body, is frequent with network of the fine collagenic fibers growing into a parenchyma from fibrozirovanny portal paths and also mesh fibrosis (pericentral, perivenous) segments and focal (mesh and not mesh) fibrosis of a parenchyma. More rare, in cases of treatment of an acute and subacute atrophy, the hepatomegalia is caused by grubouzlovy fibrosis; sometimes the hyperplasia and a hypertrophy of cells of a liver is the cornerstone of it.

Chronic hepatitis

Chronic hepatitis develops in 5 — 10% of cases after the postponed acute process, is more often after severe, long forms of a disease (especially than hepatitis B), in the presence of associated diseases went. - kish. a path and bilious ways, the previous alcoholism, intoxications. Hron. It is possible at the elderly people who are late hospitalized in a hospital, and also insufficiently intensively treated in the acute period or early started physical. to work. Formation hron. It is observed or after the icteric period or the period of reconvalescence, or after clinically stage of latency, in certain cases — without the previous acute stage (so-called initially chronic). The symptomatology hron, hepatitis generally repeats symptomatology acute, especially during the periods of aggravations, the Crimea the prodromal phenomena inherent to an acute hepatitis can precede. The patient complains of weakness, especially in the mornings, fatigue, feeling of weight and pain in the pit of the stomach, the dispeptic phenomena — loss of appetite, intolerance of greasy food, abdominal distention, nausea, a diarrhea. At the expressed aggravations jaundice, an itch, weight loss, periodic fever are noted. The liver is constantly increased, with a smooth surface, painful; increase in a spleen is defined less often, occasionally — a phenomenon of «vascular asterisks» and «hepatic palms». The giperfermentemiya, a disproteinemia with a hypergammaglobulinemia, shifts of sedimentary tests, increase in content of immune globulins testifies to activity of process. At a laparoscopy the liver is found «big white» or «big motley», it is frequent with nodes of regenerates, with defeat of both shares or only one. There are two forms hron.: perepetiruyushchy, or high-quality, with possible recovery and hron, active, or progressing, from the outcome in cirrhosis with remissions and aggravations.

Viral cirrhosis is a rare outcome (0,8 — 1% of cases), but occupies the considerable specific weight (3/4 all cases) among cirrhoses of various etiology. Often it develops years later after recovery; is one of the main reasons for development of a hepatic coma with a lethal outcome. Arises after all forms, is more often after heavy, long and recurrent. It is observed preferential at men. Among the factors promoting development of cirrhosis, the main place is taken by weight and firmness of the most viral (initial) infection and possible reinfections. Can be with various morfol, changes, however among them postnecrotic prevail. Wedge, the characteristic consists of pechenochnokletochny insufficiency, portal hypertensia, jaundice, defeat of reticuloendothelial system, hemodynamic disturbances, fever, changes from nervous and endocrine systems. Proceeding from features of development, allocate early and late cirrhosis, and also cirrhosis later it is long proceeding

the Diagnosis

Recognition of typical cases, especially in time epid, flashes, does not present special difficulties. The main objective — early and fullest identification of patients in a prodromal stage of a disease, and also patients with anicteric and subclinical forms. Diagnosis is based on a nonspecific symptom complex (dispeptic, artralgichesky, catarral and asthenic syndromes), symptoms of intoxication (temperature increase, a loss of appetite up to full anorexia and disgust for food), early emergence gepato-and splenomegalies, availability of bilirubin and protein in urine, the account epidemiol, data; an essential additional method are fermentol. researches. Big perspectives open in connection with virusol. and serol, methods, including with the methods directed to identification of antigen of hepatitis A and hepatitis B. At the height of a disease the diagnosis is confirmed by data of laboratory analyses: increase in content of direct bilirubin, the expressed globulinovy shifts, change of sedimentary tests, a giperfermentemiya, some shifts in a picture of peripheral blood (the leukopenia which is slowed down by ROE, lymphomonocytic reaction). The diagnosis of hepatitis B is based on a wedge. features (the gradual beginning, absence of fever, frequency of the artralgichesky phenomena, heavy disease with a bigger frequency of failures), establishment of the fact of the hemotransfusions made in the terms which are keeping within an incubation interval inherent to this disease, and, at last, on identification in blood of the patient with hepatitis B of the Australian antigen.

Recognition hron. And viral cirrhosis at clear a wedge, a picture is not difficult. In diagnosis latentno of the proceeding forms and at an otgranicheniya hron, hepatitis from cirrhosis tool methods — a puncture biopsy, a laparoscopy, a radio isotope research, an angiography, a reovazografiya have essential value. In diagnosis gepaty with success definition by immunopretsipitatsionny methods of alpha-fetoprotein in blood of patients is used.

In a prodromal stage it is necessary to carry out differential diagnoz with an acute gastroenterocolitis, food toxicoinfections, flu, adeno-and an enteroviral infection, rheumatism, an infectious mononucleosis; at its atypical current — with various patol. processes, including acute cholecystitis, pancreatitis, appendicitis, mental diseases, etc. In diagnosis ascertaining of development of intoxication, anorexia, the hepatomegalia, giperfermentemiya and antigenemiya inherent, and also a wedge, symptoms and datas of laboratory has the leading value (koprol., serol., mikrobiol, and gematol.).

The icteric form demands an otgranicheniye from other types of jaundices — hemolitic, mechanical, medicamentous, various hyperbilirubinemias. For hemolitic jaundice the low bilirubinovy indicator, safety of function of a liver, laboratory — signs of an increased hemolysis are inherent. Differential diagnosis with an extrahepatic cholestasia is difficult, especially in case of cholestatic hepatitis, at the same time clinical laboratory indicators and even morfol, signs cannot be rather reliable criterion. Crucial importance is attached to X-ray contrast methods: a transdermal holangiografiya (see), a retrograde holangiografiya at a duodenofibroskopiya, etc. Differentiation and medicinal damages of a liver is based on smaller duration at the last the preicteric period and the period of jaundice, bigger expressiveness of allergic manifestations in an initial stage of a disease, existence of a leukocytosis, less high hyperbilirubinemia, relative safety of function of a liver, high activity of an alkaline phosphatase; the puncture biopsy of a liver revealing an originality morfol and ultrastructural changes is more essential to diagnosis. Morfol, belongs to a method crucial importance and in an otgranicheniya from various hyperbilirubinemias.

Differential diagnosis with hepatitises at others virus (yellow fever, reoviruses, adenoviruses, a herpes simplex, etc.) and infectious diseases of the bacterial nature it is carried out in the analysis clinical laboratory and epidemiol. data in their set. Acute alcoholic hepatitis is delimited from on the basis of development of jaundice after an alcohol abuse, existence of fever, a leukocytosis, pains in an upper quadrant of a stomach on the right, originalities morfol, pictures with detection of an alcoholic hyalin.

Laboratory diagnosis

the Laboratory diagnosis based on allocation and identification of the activator or definition of specific antibodies to it is in a stage of experimental development. At (except usual blood analyses, urine, bile, a calla, etc.) enter a complex of laboratory researches biochemical, morfol, (a biopsy of a liver), immunol, and virusol. methods. At the end of a prodromal stage in blood serum of the patient increase of amount of the general bilirubin, hl is noted. obr. at the expense of the related fraction (see. Bilirubin ). In the icteric period of a disease the hyperbilirubinemia is noted. Dynamic increase in concentration of free (indirect) bilirubin and a monoglucuronide bilirubin, and also its long preservation on a high level can demonstrate heavy disease or about a possibility of approach prekomatozny or coma. The delay in normalization of these indicators in the period of reconvalescence characterizes partial reduction of function of a liver. At the beginning of the icteric Period of a disease in urine the bilirubin (which is absent normal), urobilinigen (on dark color of urine) is defined. The combination of jaundice to dark color of urine, free of bilirubin, indicates hemolitic genesis of jaundice. The amount of stercobilin in Calais (the decoloured excrements) goes down.

In blood serum of healthy faces activity of alaninaminotranspherase (ALAT) makes 36±25 units, asparaginaminotransferaza (ASAT) — 40±24 pieces. Already in the early period of a disease increase in activity of these enzymes, especially ALAT is noted. De Ritis's coefficient, i.e. the relation of ASAT/ALAT, as a rule, less than 1 (at healthy 1,3 — 1,4).

Such enzyme as zymohexase — is normal fruktozo-1-fosfatal-dolaza (F-1-FA) — in blood serum is not found or defined in trace quantities (0,15+0,07 units), and at the height of a disease its activity increases practically at all patients, especially in the first week of a disease. Le Dang Ha and L. K. Sirina observed decrease of the activity of enzyme at increase in content of bilirubin in blood serum. This phenomenon was noted at adverse disease.

In blood serum of healthy faces, except children of 1 — 3 month, activity of an urokinase (UK) is not found. In the first days of the icteric period of UK it is found (from 1 to 18 units of activity) practically in all patients. In the period of reconvalescence activity of enzyme decreases approximately at a half of patients. At jaundices of other etiology activity of UK is insignificant.

Activity of a glutamatdegidrogenaza increases at easy forms of a disease by 11 times and even more increases at severe forms.

Also activity of a lactate dehydrogenase (LDG) is defined. By method of an enzimoelektroforez it is established that LDG-4 and LDG-5 fractions considerably raise at 98 — 99,2% of patients, especially in the first two weeks of a disease. In the period of prekomatozny and coma activity of LDG-5 at the patient sharply decreases, up to normal indicators that it can be used for the assumption of the forecast of disease.

At differential diagnosis It is important to mean that activity of LDG-5 remains normal or slightly raised at obturatsionny jaundices, cholecystitises, tumors of a liver. Activity of the ornithine-karbamoil-transferase (OK) in blood serum increases at patients, especially in the first decade of the icteric period and decreases to 6 — the 7th decade depending on weight of the previous process to normal indicators.

Activity of a guanindezaminaza or guanaza (State Duma) in blood serum on average 2,15±0,14 MME (The international milliyedinitsa). In the heat of a disease activity of enzyme increases to 95 MME and decreases to normal indicators in the period of reconvalescence. Increase in activity of the State Duma at diseases of a liver of not virus etiology is not observed.

The Histidine-ammonia-lyase (HAL) normal in blood serum is not found. The maximum giperfermentemiya — at the height of a disease. At dynamic research G is SCARLET — one of criteria of weight and an outcome patol, process at.

The picture of a proteinogramma at Is a little specific. The size of coefficient albumine/globulins at in is reduced. Owing to disturbance of belkovoobrazuyushchy and belkovokompleksiruyushchy function of a liver in the acute period of a disease the high coefficient is noted (betas lipoproteids / alfa-lipoproteidy (E. M. Tareev and soavt., 1970, etc.). Decrease α and β-lipoproteids is noted at a massive necrosis of a parenchyma of a liver. Valuable data gives also definition in dynamics of glycoproteins in fractions of blood serum. For definition of glycoproteins — important complex connections (squirrels + + carbohydrates) — the diphenyl the amine reaction which is increasing at in the first 10 days of a disease and normalized at favorable disease in the period of recovery is used. Falloff of difenilaminovy reaction at a simultaneous high level of bilirubin in blood serum can demonstrate development of an acute massive necrosis of a liver (A. F. Blyuger, 1970).

The thymol turbidity test reflects to a certain extent extent of cytolytic processes in a hepatic parenchyma. Increase in indicators of test is noted in the first weeks of a disease more than at a half of patients. A bit later sublimate test changes (see. Coagulative tests). Its maximum indicators are noted usually at the height of a disease. Positive timolovy and sublimate tests are registered at active shapes and cirrhoses of a liver and are negative at hemolitic jaundices. On the contrary, flokkulyatsionny test of Irgl (1957) is usually negative at and is positive at the jaundices caused by tumors.

In a complex with other methods Veltmann's reaction (see Veltmann coagulative test) based on the changed stability of proteins of serum in relation to solutions of salts of calcium and also definition of sulphhydryl groups in serum proteins is sometimes applied (I. D. Mansurova, 1967; A. F. Blyuger, 1970, etc.) which quantity is reduced at patients depending on weight of a current.

From biochemical, the methods studying disturbances of a lipometabolism definition in blood serum of patients the general and efirnosvyazyvayushchy is more often used cholesterol (see). The amount of the general and free cholesterol is often reduced, decrease in coefficient of esterification is observed.

For identification of patients with an anicteric form definition of a spontaneous fruktozuriya is reasonable.

For studying of a blood coagulation definition is used prothrombin time (see), prothrombin (see), prothrombin ratio, proaktsellerin, proconvertin, fibrinolitic activity of blood, quantity of thrombocytes, etc.

At acute definition of immune globulins (Ig) in blood serum of patients shows their increase. The ratio of IgM/IgA at most of patients in the acute period exceeds 1,0.

Diagnostic value can have detection in blood serum of the specific hepatic and nonspecific fabric proteins appearing in the period of a heat of a disease. At the height of a disease, and especially at acute dystrophy, the liver loses a significant amount of proteins. For detection of antihepatic antibodies are used various immunol, reactions, including gel immunoadsorbents.

Definition of alpha-fetoprotein for diagnosis of primary cancer of liver and differential diagnosis and primary cancer of a liver is widely used. At fetoprotein it is found approximately in 12% of cases and, unlike primary gepaty, in most cases disappears from blood serum in the period of reconvalescence. In diagnosis of hepatitis B

definition of the Australian antigen which is found during the acute period of a disease in considerable number of patients with hepatitis B is important.

Valuable information on a condition of a liver is given intravital morfol, by a research by means of a biopsy, edges shall be appointed taking into account indications and contraindications.

Treatment

At acute timely hospitalization with observance of a bed rest — one of the conditions defining successful treatment and an outcome. A diet — carbohydrate-rich (300 — 500 g), proteins (80 — 100 g), high-calorific (apprx. 3000 kcal). Restriction of proteins in a diet is shown only at severe damages of a liver with a high level of ammonium in blood and at development of a coma. The fats which are especially emulsified at good tolerance are not recommended to be limited. At persistent vomiting — feeding via the probe, intravenous administration of 10 — 20 — 40% of solutions of glucose, in the form of drop enemas of 5% of solution and subcutaneously with equal quantity fiziol, solution (1 — 2 l and more liquid in days). The diet is appointed also in the period of dispensary observation within 6 — 12 months. Administration of amino-acid mixes from irreplaceable amino acids, Hydrolysinum, Amincrovinum, Aminopeptidum, the TsOLIPK protein hydrolyzate is shown only with proteinaceous deficit. The balanced vitamin therapy is necessary for impact on metabolic processes: thiamin, a pyridoxine, Riboflavinum, ascorbic to - that in physiologically optimum ratios. With the same purpose cocarboxylase, ATP, alpha and lipoic, orotovy, pangamovy to - you is appointed. At the dispeptic phenomena alkaline drugs are shown, at sleeplessness — barbiturates of short action, for simplification of an itch — holestiramin. Glucocorticosteroids (Prednisolonum in a daily dose of 20 — 40 mg, a hydrocortisone on 100 — 200 mg) are shown at a heavy and long current with the expressed phenomena of intoxication, and also in the absence of improvement from other methods of treatment, to patients in a prekomatozny state, at cholestatic hepatitis and in case of transition acute in hron. phase. The Prekomatozny state demands urgent increase in a dose of hormonal drugs — Prednisolonum to 100 mg a day, a hydrocortisone to 500 mg (at their intravenous administration). At the same time appoint the L-glutamine normalizing exchange of phenylalanine, glutaminic to - that. The complex of the actions recommended at a liver failure provides also correction of acid-base equilibrium, giperammoniyemiya, electrolytic imbalance and imbalance of microelements, colloid osmotic pressure of plasma and a hypovolemia, capillary blood-groove, a hypoxia, factors of coagulant system of blood, prevention and fight against infectious complications, etc.

Treatment of patients and viral cirrhosis shall be pathogenetic, directed to mechanisms of development of separate syndromes — ascites, portal hypertensia, hemorrhagic diathesis etc., and, therefore, provides use of the means applied at treatment acute. Carbohydrates remain a basis of a diet; a ratio of proteins, fats and carbohydrates 1:1:5 at 80 — 100 g of protein a day and the general caloric content of food within 3500 kcal. Use of lipotropic drugs (methionine, sincaline, etc.) is shown only at treatment by corticosteroids for prevention of fatty dystrophy of a liver. Treatment by drugs of a liver is appointed only at the compensated process. The edematous and ascitic syndrome demands use of Aldactonum in combination with tiazidovy diuretic, Mannitolum at restriction of sodium chloride in food, administration of proteinaceous drugs. At bleeding from veins of a gullet the general haemo static measures, a tamponade are recommended by a special cylinder, and at its failure — an operative measure. At a hypersplenism appoint steroid hormones, pentoxyl, transfusions of a leukocytic and platelet concentrate. Treatment by corticosteroids is shown in initial stages hron. During the progressing active hron, hepatitis, the expressed intra hepatic cholestasia, in an edematous and ascitic stage of cirrhosis (Prednisolonum of 20 — 30 mg, a hydrocortisone of 80 — 100 mg a day). They should be combined with anabolic steroids and cytostatics — Azathioprinum, cyclophosphamide, anti-lymphocytic globulin.

The forecast

In most cases comes to an end with an absolute recovery (69 — 90%) with recovery of structure and functional capacity of a liver in terms from 3 — 6 to 12 months after the end of the icteric period. Heavier and often irreversible states are hron, active hepatitis and viral cirrhosis, an acute and Subacute hepatatrophia from the death or formation (in case of a subacute atrophy) acute cirrhosis.

Prevention

the General dignity. - the prof. of an action and a measure at detection of the patient are identical both at hepatitis A, and at hepatitis V. Spetsificheskaya gamma globulinovaya prevention is carried out only at hepatitis A, screening of donors and the strengthened sterilization of tools — only at

the hepatitis B. San. - prof. of an action come down to constant surveillance over catering services, water supply, removal of sewage and to extermination of flies. Special attention is paid to protection of water sources and foodstuff against pollution by excrements of patients or virus carriers.

The particularly important becomes a dignity. promotion, instilling gigabyte. skills to adults and children, an explanation of the mechanism of transmission of infection at, acquaintance with individual measures of prevention.

Protivoepid, actions are persons, the diseased or at which suspect this disease, immediately are hospitalized and located in separate chambers or boxes of infectious diseases hospitals. Transportation of patients is made by special transport. Write out patients not earlier than the 28th day from an onset of the illness or for the 21st day from the beginning of jaundice. The had persons are allowed to work on objects of food, water supply, in child care facilities, and also children in child care facilities after an absolute recovery, but not earlier than in a month from an onset of the illness. For convalescents dispensary observation within 2 years, and if necessary is conducted more.

Before hospitalization of the patient in the center final disinfection is carried out current, and after its hospitalization. Bedding and outerwear are disinfected in a disinfection chamber. The room is irrigated from the hydropanel of 3% with solution of chloroamine or 0,2% solution of dichlordimethylhydantoin with sulphanole; the bathtub, a toilet bowl and so forth are wiped with the rags moistened hot 2% with soap and soda solution. Allocations of the patient fill up with dry lime chloride or hypocalcium chloride (DTSGK); in water after washing of the patient fill DTSGK or chloroamine respectively 200 — 300 and on a bucket of water.

In the center it is carried out epidemiol. inspection for the purpose of identification of a source of a contagium, ways of distribution of an infestant and definition necessary protivoepid. actions in the conditions of a specific epid, the center. Early detection of a source of a contagium (patients and virus carriers)' in child care facilities, on objects of food and water supply is important. It is necessary to consider probability of existence in the center of patients with subclinical forms. In the center medical observation on 45 days from the date of hospitalization of the patient is established. At emergence in child care facility (a garden, a day nursery, sanatorium, a hospital) group, in a cut there were diseases, isolate on 45 days: during this term reception of children in group or transfer of children of group in other collectives is not made.

Apply gamma globulin to specific prevention of hepatitis A. Numerous observations confirmed J. Stokes's data on his useful effect at mass prevention of hepatitis A. If this drug not always has protective action, then, as a rule, softens a wedge, displays of a disease, but on condition of its correct dosage. Gamma globulinovaya prevention of hepatitis A is carried out in predepid. the period and in epid, the centers from calculation that drug can be useful, though to a lesser extent, even in an incubation interval — in 6 days (deadline) before emergence of symptoms of a disease. Generalizing long-term experience, WHO experts recommend 0,02 ml of 16% of solution of gamma-globulin for 1 kg of weight as the minimum preventive dose; 10% solution of drug are manufactured in the Soviet Union.

At direct contact of e sick the dose increases by 4 — 6 times. In cases of the threat of infection which is dragged out in time it is recommended gamma globulinovuyu to repeat prevention in 2 — 3 months. On immunol, activities gamma-globulins are more or less identical, but activity of their different series is not unambiguous.

Duration of preventive effect of gamma-globulin is defined in 3 — 6 months. So long term of protection is explained by probability of the vaccinating action of the virus which got into an organism which is partially neutralized by antibodies, i.e. passive active immunization. The vaccination against hepatitis A yielding the encouraging results in an experiment remains undeveloped so far.

Special measures of prevention: as the main measure of protection from hepatitis B serves careful sterilization of all medical tools.

It is established that even the insignificant share of serum or a blood plasma of the carrier can cause a disease in the person. The thermal stability of a virus demands or long, not less than 30 min., boiling, or autoclavings. It is impossible to replace these measures with disinfectants or alcohol.

After development of various methods of detection of the Australian antigen the real possibility of identification of virus carriers and selection of donors appeared. The people having the Australian antigen in blood shall be eliminated donors, as well as the people having in the anamnesis a disease. The perspective of preparation of immunoglobulin by use of blood from donors in whom the Australian antigen in a high caption, or after preliminary vaccination of donors is found by the inactivated Australian antigen opened. The inactivation of antigen in serum of virus carriers is made by warming up of serum at a temperature close to boiling. Use of the heated-up serum containing the Australian antigen or its protein fraction which lost pathogenicity, but kept an immunogenicity serves as the only justification of a possibility of creation of a vaccine so far. Attempts of receiving for this purpose of cultures of the Australian antigen out of an organism did not yield positive takes.

The viral hepatitis at pregnant women

takes the main place among jaundices at pregnant women (57,1%); less often various diseases of a liver, bilious ways and hemolitic anemias (16,0%), some options of pathology of pregnancy (26,9%), napr, a rare syndrome of an acute fatty hepatosis of pregnant women and more widespread cholestatic hepatosis of pregnant women which is characterized by a peculiar symptom complex of an intra hepatic cholestasia (tab. 3) meet.

Pregnancy does not raise a susceptibility to, but in connection with frequent diagnostic and to lay down. manipulations danger of emergence at pregnant women increases; HB antigen is found in them to a thicket (to 77,4% in early stages of hepatitis).

Against the background of pregnancy keeps all inherent in it a wedge. lines. At late durations of gestation in an acute stage of a disease there is a gepatodistrofiya more often, and in the postical period hron, hepatitises and cholecystitises form more often. Pregnancy in combination with gives high rates of a nedonashivayemost, frequency a cut is in a feedforward with weight of hepatitis. Uterine bleedings meet seldom. Indicators of a maternal lethality at remain high in the Mediterranean countries with pregnant women and in Asia — to 7,7%, and in Europe 1,8% [Martini and Balttser (G. Martini, G. Baltzer), 1972]. In Moscow this indicator decreased to 0,5%.

The possibility of transfer from mother intra-or is postnatalno completely proved to the child. The mechanism of infection is connected first of all with hit of blood of mother from patrimonial ways to a blood stream of the child through matserirovanny sites of his skin. The possibility of transplacental transfer is not proved yet; systematic observations in conditions when intra-or post-natal infection is minimized, did not possible to reveal clinically shown neonatal hepatitis for the first 5 — 6 weeks of life. Searches of antigen to hepatitis B in umbilical blood of newborns by highly specific test — a precipitation test in gel — in most cases yield negative takes. However completely it is impossible to exclude a possibility of a transplacental infection at since a number of its nonspecific indirect signs comes to light: increase in the average level of IgM in umbilical blood, the strengthened erythrogenesis not only on the course of capillaries, but also in portal paths of a liver perinatalno the died fruits, HB antigen in a liver mortinatus, found in some cases by method of immune fluorescence. Descriptions of inborn hepatitises which quite often try to connect retrospectively with an asymptomatic current at pregnant women, cause objections. Neonatal hepatitises and giant-cell transformation of hepatocytes can be caused not only by a virus of hepatitis, but also cytomegaloviruses, a herpes simplex, chicken pox, a rubella, a koksaka, etc. [G. Monif, 1969], and also hereditary defects of exchange (e.g., alfa1-anti-tryptic insufficiency).

Treatment at pregnant women is based on the general principles of therapy.

The prevention of bleedings at pregnant women is reached by treatment of a basic disease with rational use of the means reducing a uterus. Acute is not the direct indication for abortion. In the absence of effect of the carried-out treatment pregnancy shall be interrupted. The organization of complex medical aid with provides to pregnant women in most cases a favorable outcome for mother and the child.

Prevention at pregnant women assumes (in addition to the general precautionary actions) the accounting of the increased risk of infection at planned blood tests, stomatol. help and other tool interventions. The pregnant women who were in contact with patients shall receive intramusculary gamma-globulin.

The viral hepatitis at children

Is eurysynusic among children. From all diseased 60% and more are the share of children aged up to 15 years. More often incidence is observed at children of preschool and younger school age. Children of the first year of life are ill much less often, however also newborns can be ill. At children of the first year hepatitis B is observed almost only, at children is more senior than two years — preferential hepatitis A.

Incidence at children is characterized by autumn and winter raising, formation of the centers in child care facilities.

A wedge, manifestations at children of advanced age are similar to a picture of a disease at adults. However at children the acute beginning with short-term (2 — 3 days) temperature increase is more often noted. The preicteric period is shorter, than at adults, usually does not exceed 5 — 7 days and is characterized by a combination astheno - vegetative symptoms: slackness, weakness, irritability, increased fatigue, nausea, sometimes vomiting, small appetite, abdominal pain. Are sometimes observed poorly expressed catarral Ivleniya from upper respiratory tracts. An early symptom — increase in a liver, is frequent also spleens. At the end of the preicteric period color of urine and a calla changes. Arthralgias in the preicteric period at children happen very seldom.

Jaundice accrues quickly enough and in 5 — 7 days usually reaches a maximum. In most cases the icteric period proceeds 2 — 3 weeks. The itch of skin at jaundice at children is observed considerably less than at adults.

Comparison of clinic of hepatitis A and hepatitis B shows that hepatitis A is characterized by more acute onset of the illness (fever, vomiting, abdominal pains) and bystry disappearance of symptoms of intoxication by the time of emergence of jaundice. Icteric period rather short. The gradual beginning with slower development a wedge, symptoms, gradual strengthening of intoxication in process of progressing of a disease, more long (apprx. a month) the icteric period, a long hyperbilirubinemia and a giperfermentemiya, a resistant gepatosplenomegaliya, big frequency of the residual phenomena and at the same time lower indicators of a thymol turbidity test is characteristic of hepatitis B.

The originality of clinic and the course of hepatitis B in age aspect comes to light a nek-swarm, and especially children of the first year have lives at which it is considerable more often than at children of advanced age, severe and medium-weight forms are observed.

Hepatitis B at children of the first year of life begins more sharply; in the preicteric period temperature increase, vomiting, vomiting, a liquid chair, a loss of appetite, a sleep disorder, concern, slackness are more often observed. Symptoms of intoxication continue to amplify also at emergence of jaundice while at children of advanced age with the advent of jaundice symptoms of intoxication usually weaken. Jaundice at children of the first year of life accrues quicker, than at the senior children; the amount of bilirubin and activity of enzymes in blood serum reach the maximum quicker. Also increase in a liver at children of the first year of life is considerably more expressed, and almost in all cases increase in a spleen (at children of advanced age the spleen is palpated only in 50% of cases) is noted.

Weight of a current Is estimated at children in an initial stage, but not earlier, than the wedge, symptoms inherent to this disease will develop all; also manifestations of the preicteric period of a disease are considered. Along with a wedge, symptoms at assessment of weight also indicators of functional trials of a liver shall be considered.

Severe forms Are characterized by more bystry course of a disease (the short preicteric period), the expressed intoxication. Increase in a liver, intensity of jaundice are also indicators of weight. More objective criterion of weight is extent of increase in content of bilirubin in blood serum, and especially free bilirubin, and also extent of increase in activity of organospetsifichesky enzymes, (beta lipoproteids, decrease in a prothrombin and disturbance of other biochemical indicators of a functional condition of a liver.

Children of the first year have lives at similar weight of a disease intensity of jaundice and a hyperbilirubinemia are less expressed, than at children of advanced age. It is explained probably by the fact that weight of a disease at them is caused by disturbance not so much of pigmental exchange, how many other exchange processes (acid-base equilibrium, water and electrolytic, proteinaceous, etc.); these disturbances arise much quicker and are more expressed because of imperfection of mechanisms of compensation.

Special difficulties in diagnosis at children arise in the preicteric period and in cases of the anicteric and erased forms. In addition to a characteristic combination astheno - vegetative symptoms with increase in a liver and spleen special value for early diagnosis has increase in activity of enzymes (fruktozo-1-fosfataldolazy, fruktozo-1-difosfataldolazy, alanine - and aspartate aminotransferases, etc.), and also increase in maintenance of beta lipoproteids, indicators of a thymol turbidity test, etc. Increase in content of bilirubin in blood serum comes to light only at the beginning of the icteric period. Diagnosis at children in the icteric period usually does not represent special difficulties.

In the preicteric period it is necessary to differentiate with acute respiratory viral diseases and diseases of biliary tract more often. The greatest difficulties in diagnosis arise at children of the first year of life, and especially the first months. In these cases it is necessary to differentiate it with inborn hepatitises of a different etiology (cytomegalic, toksoplazmozny and herpetic) and an atresia of bilious ways.

Gepatodistrofiya and lethal outcomes are noted almost only at children of the first year of life, and is preferential in the first 6 months.

Treatment of children with lungs and in most cases with medium-weight forms can be limited to purpose of a bed rest, sparing and full fiziol. diets, plentiful drink, weak solutions of glucose and alkaline mineral water, complex of vitamins (C, B 1 , B 2 and B 6 ), the drugs having cholagogue and aperient effect. At severe forms there is a need of intravenous drop administration of liquid (5 — 10% solution of glucose with Ringer's solution in the ratio 2:1), Neocompensanum, Haemodesum, plasma, albumine, cocarboxylase. At a metabolic acidosis intravenous administration of 4 — 4,5% of solution of sodium bicarbonate is appointed. It is better to appoint hormonal drugs (Prednisolonum at the rate of on average 2 mg a day) to 1 kg of weight a short course (10 — 12 days). At children of the first year of life of the indication to purpose of Prednisolonum shall be expanded; in the presence of the state burdened premorbidal it is necessary to appoint them also at medium-weight forms.

The forecast is very serious at children up to one year at whom is at severe forms a high lethality. Children of advanced age have a current and outcomes same, as at adults.

Tables

Table 1. The CHARACTERISTIC of HEPATITISES A and In ON SOME INDICATORS


Table 2. INCIDENCE of the POPULATION of the USSR of the VIRAL HEPATITIS for 1953 — 1974 (on 100 thousand people)


Table 3. DIFFERENTIAL and DIAGNOSTIC CHARACTERISTIC of the VIRAL HEPATITIS AND CHOLESTATIC HEPATOSIS of PREGNANCY



From additional materials

the Term «viral hepatitis» combines a number of diseases, the general sign to-rykh is damage of a liver under the influence of viruses. Accurate classification of a viral hepatitis of the person does not exist yet as they are studied insufficiently fully. As independent nosological forms allocate hepatitis A and hepatitis B. Besides, various hepatitises combined in the «hepatitis And, In» group are known a little etiologically. The concept «hepatitis And, In» means that the diagnosis of hepatitis A or B is excluded according to specific diagnostic tests. Carry also viral diseases to a viral hepatitis, at to-rykh damage of a liver is a component of a generalized infection — yellow fever (see), Lass's fevers (see Lassa-likhoradka), Marburg (see Tser-kopitekovaya hemorrhagic fever) and Ebola (see Ebola hemorrhagic fever), the diseases caused by viruses of herpes (see. Herpes infection) and Koksaki's viruses (see Koksaki-virusnye of a disease), measles (see), a rubella (see), etc.

Hepatitis A. An etiological agent of hepatitis A is the virus, to-ry, according to all taxonomical characteristics, belongs to this. picornaviruses (see. Intestinal viruses). Mature virions of a virus of hepatitis A (the size apprx. 27 nanometers) are constructed as ikosaedralny symmetry. The fibrous casing of a virus consists of 32 base units (capsomeres). In the biochemical analysis as a part of a virus four polypeptides having the molecular weight (weight) similar in size with a molecular weight of polypeptides at typical picornaviruses come to light. The genome of a virus is positive and presented to one-spiral RNA with a molecular

weight of 2,25 X 106. The ways of cultivation of a virus of hepatitis A in cellular systems based on special adaptation of a virus by a long incubation of culture of the infected cells or on weak «traumatization» of cells before and after infection with a virus are developed. In both cases reproduction of a virus proceeds without cytopathic changes.

For statement etiol. the diagnosis of hepatitis A use solid-phase radio - and enzyme - immunological methods (see. Radio immunological method, Enzyme-immunological method), and also immunoelectron microscopy (see the Submicroscopy). The virus in allocations of the patient is possible to find in the second half of an incubation interval less often in the first days after emergence a wedge, symptoms of a disease (in particular, jaundices). Increase of antiserum capacities comes to light approximately at one third of patients, antibodies at hepatitis A are, as a rule, formed very much early and quickly reach high credits. As the most reliable diagnostic test serves definition of specific antibodies of a class M. They are defined from the first days of a disease and remain in an organism of the patient up to 4 — 6 months therefore finding of such antibodies demonstrates recent infection of the person with a virus of hepatitis A. Use of methods of detection of a virus of hepatitis A and antibodies to it allowed to expand ideas of epidemiology of hepatitis A significantly. So, it was established that the ratio of asymptomatic (subclinical) forms of an infection and clinically expressed (icteric) averages 10: 1 at sporadic incidence and 1: 1 or even 1:5 during large flashes. Asymptomatic forms most often occur at children of early age. It was shown also that formation of immunity of the population to a virus of hepatitis A is subject to considerable fluctuations depending on medico-geographical and sanitary and hygienic factors. As the general pattern is traced increase in a share of immune (seropositive) persons in the senior age groups, and antibody formation happens more intensively in districts to hot climate and on less well-planned in a dignity. - a gigabyte. relation territories. The gamma-globulins of serial production received from blood of a large number of donors have rather high credits of specific antibodies against a virus of hepatitis A that is explained by the big frequency of immune persons among donors.

Successful cultivation of a virus of hepatitis A in cultures of cells opened possibilities of development of specific vaccines from the inactivated virus or from attenuirovanny options of a virus. Such vaccines pass tests.

Hepatitis B. The causative agent of hepatitis B represents a virus, unusual on the structure and properties. It has no similar among other viruses of the person and together with viruses of hepatitises of the Canadian forest groundhogs, cape ground squirrels and the Beijing ducks forms not taxonomical group of a Hepadna-Viru-owls. The particles of a virus of hepatitis B known also under the name of particles of Dane, have an appearance of spherical education by diameter apprx. 42 nanometers. The outside viral envelope is made by a layer of a so-called surface antigen, or HBsAg (the outdated term — the Australian antigen). Under it there is a core (core) constructed of the serdtsevinny HBcAg antigen and a genome presented to peculiar ring two-spiral DNA with a molecular weight apprx. 2 X 106. In mature particles the spiralizovanny site occupies 70 — 80% of length, and on other extent of DNA of an odnospiraln. As a part of a core, besides, are defined one more antigen — HBeAg and special enzyme — a DNA-dependent DNA polymerase. In turn, each antigen has the complex biochemical structure assuming existence of antigenic variations.

At HBsAg the general is found for all isolates of a virus an antigenic subdeterminant «and» and, besides, two mutually excluding subdeterminants of «d» or «at» and «w» or «». Thus there are four antigenic phenotypes: adw, adr,

ayw, aug. At HBeAg three antigenic options are known. The virus of hepatitis B does not manage to be cultivated in cellular systems. The only animals, susceptible to virus, are chimpanzees. In understanding of the nature of a virus a lot of things were brought by molecular and biological researches, including cloning of a virus genome in bacterial cells for the purpose of reproduction of synthesis of DNA and nek-ry antigens.

Interrelation a wedge, courses of hepatitis B with virologic and serological indicators of an infection very difficult, considering variety a wedge, forms and outcomes of the disease. In typical cases at an acute disease in blood HBsAg and HBeAg are regularly defined, and their emergence can advance symptoms of a disease and rise in levels of serumal transaminases for several weeks. By means of special methods it is possible to find virus particles and the related DNA polymerase in blood. Recovery usually matches the termination of an antigenemiya (disappearance of antigens of a virus from blood) and antibody formation — ANTI-NVD, anti-NVS and ANTI-NVA. At persistent and chronic hepatitis B constant presence at HBsAg blood is noted, sometimes in the form of cell-bound immune complexes with anti-NVV-antitelami and it is frequent in combination with HBeAg. Along with antigens in blood antibodies to all or a nek-eye to viral antigens can be defined. Increase in content in HBeAg blood is characteristic of the period of an aggravation of process. Quantitative content of antigens and antibodies in blood of the infected person is subject to considerable fluctuations therefore the probability of their identification to a large extent depends on sensitivity of the used methods. The most reliable results receive by means of solid-phase radio - and en-winters-immunological methods. In detection of HBsAg and anti-NVD-antitel reaction of passive hemagglutination is rather sensitive (see). Sensitivity of immunodiffusion (see) in gel and a counter immunoelectrophoresis (see) is 100 — 1000 times lower, than at the listed methods, and it often is insufficient for identification of healthy antigenonositel (e.g., among donors), at to-rykh concentration of HBsAg in blood, as a rule, low. As a result epidemiol. observations it was proved that, except the known parenteral mechanism of infection and vertical transfer (from mother to a fruit), the virus of hepatitis B can be transmitted sexually. Other ways of infection are of secondary importance.

State hron. infection it is observed at 5 — 10% of the persons which caught a virus of hepatitis B during life. The children born from mothers, being chronic carriers of a virus very often are infected: in nek-ry ethnic groups of the countries of Asia the frequency of vertical transfer of a virus of hepatitis B reaches 70%. By estimates of WHO, in the world there are 150 — 200 million hron. carriers of a virus of hepatitis V.

Hron. infection with a virus of hepatitis B is considered also as the factor promoting developing of primary cancer of liver (see the Liver, tumors). In tropical districts clear dominance of tumors at chronic HBsAg carriers is traced (approximately by 200 times more often than at the corresponding control groups). By means of molecular and biological methods the direct evidence of presence of a genome of a virus of hepatitis B at tumor cells is obtained what assumes integration of virus DNA and participation of a virus in the course of their malignancy.

In recent years the vaccines preventing infection with a virus of hepatitis B in experiments on a chimpanzee were created. Such vaccines restrictedly applied also to immunization of people. As material for production of vaccines served HBsAg extracted from a blood plasma of healthy faces with antigen-miyey and subjected to preparative cleaning and concentration. Drug was subjected to additional chemical processing for elimination of residual infectivity. Immunogene material for a vaccine can be received from the cloned bacterial or eukariotny cells bearing a fragment of a virus genome and also direct chemical synthesis of the certain polypeptides capable to stimulate development of protective (protective) antibodies. Uniform recommendations about use of vaccines against hepatitis B do not exist yet. Consider that vaccination shall be subject the persons subject to the increased risk of infection (e.g., employees of blood transfusion stations). Also the possibility of broad vaccination of children in districts with high frequency of spread of hepatitis B where infection most often happens at early age is considered.

«Hepatitis And, In». Enter into the «hepatitis And, In» group posttransfusion «hepatitis And, In», «hepatitis And, In» with the fecal and oral mechanism of transfer, etiologically other than hepatitis A, and also delta hepatitis.

The first is connected with hemotransfusions or its products. Klin, a picture of a disease reminds hepatitis B (the long current and transition in hron are observed. current), but severe forms meet less often. The incubation interval makes, according to one data, 40 — 103 days, on others — 18 — 50 days that, perhaps, corresponds to two different infections. Etiol. agents of posttransfusion hepatitis are not fixed. In experimental conditions susceptible to an infection were only chimpanzees. In experiments on cross infection of these animals it was succeeded to show that posttransfusion «And, In» two activators, each of can cause hepatitis to-rykh does not create immunity in relation to another.

«Hepatitis And, In» is similar to the fekalnooralny mechanism of transfer on a wedge, to manifestations and a nek-eye epidemiol. to signs with

hepatitis A. As it etiol. the agent the spherical virus particles with a diameter of 27 — 30 nanometers found in excrements of patients with method of immunoelectron microscopy are described. These particles had no antigenic communication with a virus of hepatitis A. Drupsh proof etiol. differences of this hepatitis from hepatitis A the fact that the disease quite often developed at the persons which had strong immunity to a virus of hepatitis A is considered. «Hepatitis And, In» with the fecal and oral mechanism of transfer is widespread in the countries of Southeast Asia where the virus was transmitted through water in this connection there were large disease outbreaks, and preferential adult hurt. At pregnant women noted especially heavy disease from the death in one third of cases. Sporadic cases «hepatitis And, In» with the fecal and oral mechanism of transfer were registered on the European and American continents, and also in the Central Asian part of the USSR.

Delta hepatitis (more correctly, the hepatitis associated with delta antigen) causes the peculiar defective virus infecting the person along with a virus of hepatitis B. Its defect consists that it is not capable to independent reproduction, but fills the functions lacking it due to the synthetic processes which are carried out by a virus of hepatitis B. Particles of a virus have the size 35 — 37 nanometers and are constructed of the outside cover entirely consisting of HBsAg, internal protein, or actually delta antigen and small (molecular weight apprx. 0,5 X 106) by one-spiral RNA. The virus, obviously, is transmitted through blood as the delta and viral infection is especially often observed at patients, the Crimea hemotransfusions were repeatedly made. For delta hepatitis both acute, and chronic forms are described, the Crimea always accompanies hepatitis B. Hepatitis with participation of a delta virus usually proceeded heavier, than the hepatitis caused by one virus of hepatitis B (big frequency of deaths and effects in the form of chronic active process was noted). Spread of delta hepatitis is studied insufficiently fully.

Bibliography: Balayan M. S., etc.

The viral hepatitis similar on clinic and epidemiology to hepatitis A, but different from it etiologically, Zhurn. mikr., epid. and immun., No. 8, page 79, 1982; Coulepis A. G. and. lake of Biophysical and biochemical characterization of hepatitis A virus, Intervirology, v. 18, p. 107, 1982, bibliogr.; Deinhardt F. Gust I. D. Viral hepatitis, Bull. Wld Hlth Org., v. 60, p. 661, 1982, bibliogr.; Hepatitis In vaccine, ed. by P. Maupas a. P. Guesry, Amsterdam — N. Y., 1981;

London W. T. Primary hepatocellular carcinoma — etiology, pathogenesis, and prevention, Hum. Path., v. 12, p. 1085, 1981; McCollum R. W. a. Zuckerman A. J. Viral hepatitis, J. med. Virol., v. 8, p. 1, 1981; M a r-mion B. P. a. Burrell C. J. Hepatitis In and non-A, non-B hepatitis, some recent developments and unresolved problems, in book: Viral dis. in South-East Asia and the Western Pacific, ed. by J. S. Mackenzie, p. 352, Sydney, 1982; Robinson W. S. Viruses of human hepatitis A and B, Comprehens. Virol., v. 14, p. 471, 1979; Virus and the liver, ed. by L. Bianchi a. o., p. 3, Lancaster, 1980.

M. S. Balayan.



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B. D. Solovyov; B. K. Bezprozvanny (stalemate. An.), H. I. Nisevich (ped.), I. V. Rubtsov (lab.), M. E. Semendyaeva (C), N. A. Farber (gin.).

Яндекс.Метрика