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Etiology and pathogeny - Acute hepatitises

Table of contents
Acute hepatitises
Etiology and pathogeny
Treatment and prevention

In the etiological plan acute hepatitises represent diverse group.

Etiological forms of an acute viral hepatitis
The acute viral hepatitis And (infectious hepatitis, epidemic hepatitis, an infectious disease) is characterized by mainly fecal and oral way of a transmission of infection, a short incubation interval (on average 21 — 25 days), in most cases rather not heavy course, lack of a tendency to synchronization and development of a virus infection carrier state. However against old changes of a liver and its additional damages development of fulminant forms, and also a long current is in some cases possible. In particular, at the persons having alcoholism at addicts and homosexuals duration of the acute period can reach 3 — 6 months. All cases and in these supervision come to an end with recovery. In supervision with E. N. Kubensky and G. M. Gerasimov disease duration was registered more than 3 months at 13% of patients. The majority of them had also intercurrent infections.

Methods of specific diagnosis: antibodies to a virus of hepatitis of the Class A of IgM (anti-HAV IgM) appear in blood serum at the beginning of clinical manifestations and remain till 6 months.

The acute viral hepatitis In (serumal hepatitis) is characterized by mainly parenteral way of infection (the transfer mechanism), a long incubation interval (on average is possible 60 days also contact, including sexual), quite often heavy current, development of fulminant, atypical and chronic forms, and also a carriage of virus.

This viral infection proceeds with very high concentration of virus particles — to 10 trillion in cubic millimeter of blood serum. The gene device (genome) of a virus consists of four segments: The S-gene playing a code role for production HBsAg with - a gene — the HBcAg and HBeAg code, a r-gene — a code of a DNA polymerase and x - a gene quite often are found in patients at whom the hepatocellular carcinoma develops later.

Markers of viruses of hepatitis B allowed to allocate 3 conditions of a viral infection of hepatitis B.

1. Traces of the postponed infection — a condition of artificial immunity. Existence in blood serum anti-HBs, anti-HBc in low credits and anti-HBc IgG is usually characteristic.

2. Persistirovaniye of a viral infection. This state is designated also as integral or chromosomal. DNA of a virus is connected with a hepatocyte genome. In the kliniko-virologic plan these forms are designated also as unproductive or nereplikativny.
Existence in blood serum HBsAg, anti-HBc IgG is characteristic, anti-HBe in low credits is found in a number of persons. This type of a viral infection is widespread widely and is observed at a carriage of virus, i.e. at hepatitis B virus carriers (so-called antigenonositel).

3. Replication (redublikation) of a viral infection. The hepatitis B virus genome, in particular its DNA, is in so-called free, episomalny or ekstrakhromosomny situation. In this case replication or a redublikation (i.e. full reproduction — "doubling") a virus happens normally. In the kliniko-virologic plan these forms designate as productive or replikativny. Existence in blood serum HBeAg, an also of anti-HBc IgM in high concentration, HBV DNA and DNA polymerases is characteristic of replication. At most of patients also HBsAg is defined.

This type of a viral infection is widespread rather widely and is observed at clinically expressed acute viral hepatitis In, and also at the first stage of chronic active hepatitis B.

Virus and immunological signs — a basis of specific diagnosis of an acute and persistent viral infection.

1. At an acute viral hepatitis In in blood serum find: high credits of anti-HBc and (or) anti-HBc IgM; HBsAg, including HBsAg IgM; HBeAg, HBV DNA, DNA polymerase. In tissue of a liver find HBsAg, HBcAg, HBV DNA.

2. Hepatitis B virus carriage (HBsAg carriage). Its virologic characteristic is given above (see Persistirovaniye to a viral infection).

The carriage of HBsAg is widespread very widely. In the world there are not less than 300 million carriers.

Usually carry almost healthy people at whom, as a rule, accidentally (at mass inspections) find HBsAg in blood serum to carriers of a surface antigen.
Frequency of development of an antigenonositelstvo depends on a floor — men in 1 1/2 — 2 times become more often carriers, than women. The babies who had an acute viral hepatitis in 90% of cases become antigenonositel, children — in 20 — 30%, adult — in 5 — 10%.

In clinical practice quite often mistakenly carry considerable number of patients with rather oligosymptomatic diseases of a liver to carriers of a surface antigen. Both on our supervision, and according to literature, about 40% of the persons which are originally regarded as aitigenonositel also appear those. Among other 60% most often reveal chronic persistent and lobulyarny hepatitises, and also an acute viral hepatitis. The special attention is deserved by chronic active hepatitis and cirrhosis which are observed at 5 — 7% of so-called antigenonositel. Therefore all aitigenonositel at whom reveal markers of a replicative (active) form of a viral infection (HBeAg HBV DNA, a DNA polymerase, etc.), and also persons at whom manifestations of cytolytic and mesenchymal and inflammatory syndromes are registered have to be subjected to detailed inspection, including a puncture biopsy of a liver.

In general signs of various forms of a chronic HBV infection are found in 5 — 10% of the inspected adult population of the globe. Today exact establishment of a form of a viral infection and character of a disease of a liver at this specific patient belongs to important tasks. It defines nature of medical actions and the forecast.

D-hepatitis (delta agent) is caused by the defective virus capable to replication only in the commonwealth with a hepatitis B virus. Always it is found along with a hepatitis B virus, considerably making heavier a current of part of acute and chronic forms of a disease.
Methods of specific diagnosis; antibodies to a delta virus (anti-HDV).

Acute viral hepatitis And Century. Emergence of methods of specific diagnosis in 1974 — 1975 showed that not all acute viral hepatitis belongs to hepatitises A and B. Concerning this group of hepatitises available methods of specific diagnosis were not developed until recently and therefore they are carried still more often to rather uncertain hepatitises "And In" in the terminological plan.

Various systems of division of hepatitises And are assumed Century. We use following: hepatitis C, sporadic (epidemic) form of hepatitis And Century.

Acute viral hepatitis of S. V of 1978 of R. Shiraki and soavt. and almost at the same time F. G. Renger and soavt. allocated a new form of hepatitis which was called hepatitis C. Though with success A. M. of Prince (USA) and Ch used the test system created by these researchers. Trepo (France), however lack of public test system and convincing characteristics of a virus prevented the general recognition of these data.

Only in 1989 results of long-term researches of the working group M. of Haugthon (the USA, California) which managed to allocate the activator of this form of a viral hepatitis were published and to create the test system allowing to define anti-HCV. It was established that antibodies to a virus appear in 6 — 12 months after the beginning of an acute infection. Therefore the main advantage of this test — a possibility of identification of chronic forms of an illness.

On the basis of the obtained data it is possible to consider established that the parenteral way of transfer whereas the possibility of a contact way of transfer does not find sufficient confirmation yet is characteristic of an acute viral hepatitis With. Incubation interval about 60 days. The acute period proceeds slightly easier, than at hepatitis B, however long and chronic forms are observed more often.

Many data indicate the frequency of the postponed acute viral hepatitis With at men of addicts and patients with hemophilia. The relative rarity of detection of anti-HCV at homosexuals testifies to smaller value of sexual transmission. The great interest is caused by the frequency of detection of this marker in patients with autoimmune chronic active hepatitis. The assumption that the considerable part of these diseases is possibly connected with a viral infection received confirmation.

Sporadic (epidemic) form of hepatitis And V. S mainly in Central Asia are described 1978 cases of an acute hepatitis according to kliniko-epidemiological characteristics, very close to an acute viral hepatitis of A. Otlichayetsya by heavier current at pregnant women and exhausted. In series of observations it were sporadic forms, in others — epidemic flashes. Therefore in the name there are, apparently, mutually exclusive characteristics — a sporadic (epidemic) form.

Methods of specific diagnosis (an antibody to a virus) some virologic institutes in the world have so far. Therefore practically this form of a disease is assumed in cases of an acute viral hepatitis of a fecal and oral way of the infection inclined to epidemic flashes at which methods of specific diagnosis allow to exclude reliably hepatitis A (anti-HAV IgM), an also hepatitis B (HBsAg, anti-HBe).

Acute alcoholic hepatitis
The damaging effect of alcohol on a liver is known long ago.
Acute alcoholic hepatitis usually develops after hard drinking. Often the patient not unsuccessfully tries to hide the drinking habit therefore indication of intoxication alcohol is important from the doctor.

Allocate direct indication — definition of ethanol in blood serum. This research needs to be carried out first of all in receptions of hospitals.
A certain value and indirect indication keeps. A little conditionally it can be divided into indication chronic and indication of acute intoxication alcohol.

Indirect indication of chronic intoxication alcohol. At survey often reveal a congestive dermahemia and expansion of hypodermic vessels of the person, gray-brown coloring of skin of a neck ("the tramp's neck"), a tremor of hands, a century, language, a gynecomastia, a palmar fibromatosis, increase in parotid glands. Besides, quite often find a tendency to unstable arterial hypertension, often register symptoms of chronic pancreatitis and polyneuropathy.

From laboratory tests naturally define: increase of activity of GTTF (GGTP) of blood serum, increase of concentration of uric acid of blood serum; increase in average volume of an erythrocyte ("average volume of a cell"); increase in concentration of urobilin of urine.
Increase of activity of GTTF is observed at 80%, change of three other tests — at 60 — 65% of persons with chronic intoxication alcohol.

Indirect indication of acute intoxication alcohol. At survey of the patient no later than 12 — 36 h after the end of hard drinking of change of language are observed at 90 — 95% inspected. Language is edematous, covered with a dense white plaque; the small tremor of language is characteristic. At the use of a large number of hard liquors language sometimes dry, is covered with a black scab. At most of patients arterial hypertension and a tendency to tachycardia is observed at the same time.

Hyperactivity of a glutamatdegidrogenaza (GDG), aminotransferases and amylase of blood serum.
Clear change of the listed tests is observed at 90% of patients, however at considerable part these changes are registered for only 24 — 48 h. Further at most of patients they in different terms are normalized. The last three tests use in a hospital for control of observance by patients of the mode of abstinence.

Acute medicinal hepatitis
The leading role in biotransformation from the outside of the arriving substances — xenobiotics — belongs to a liver, in particular, its microsomal system, including R-450 cytochrome. Drugs also belong to xenobiotics. The mechanism of transformation of xenobiotics in a liver proceeds in two phases. In the first — substances are exposed generally to oxidation or recovery. In the second phase they unite to the remains of glucuronic or sulphuric acid, amino acids, etc. Pass into a soluble state. Usually at the same time lose poisonous properties. In development of acute medicinal hepatitis, except character of medicine (see below), the sochetannost and duration of their use and especially — the previous injuries of a liver play a role.

There are offers to divide medicinal injuries of a liver into two groups: as a result of the direct hepatotoxic action of drugs and indirect influence connected with immune disturbances (hypersensitivity).

Treat the acute medicinal hepatitises connected with acute hypersensitivity caused by penicillin, streptocides. Treat the hepatitises caused by hypersensitivity of the slowed-down type caused gidrolaziny (Depressanum), etc. Paracetamol has direct toxic effect on a liver.

However there is a number of drugs which damaging action does not manage to be referred to any group unambiguously. In this regard it is necessary to allow a possibility of various pathogeny of the medicinal hepatitis which resulted from use of the same medicine.
There is not clear a reason why women 2 — 3 times more often have acute medicinal hepatitises, than men.

Acute medicinal hepatitises are caused by numerous drugs. The most severe forms of the medicinal hepatitises proceeding with necroses of a hepatic parenchyma can result from use of a dopegit, Tubazidum (isoniazid), rifampicin, paracetamol, Isapheninum, Nialamidum, a methotrexate, Ftorotanum, a furadonin, dipheninum and Depressanum. Less severe forms of acute medicinal hepatitises cause antibiotics (leaomitsetin, tetracycline, gentamycin; tseporin, etc.), other antibacterial agents (5-HOK, Sulfasalazinum, Bactrimum, etc.), drugs for treatment of cardiovascular diseases (Intensainum, indirect anticoagulants, inderal, quinidine, etc.), saluretics (a dichlothiazide, Acidum etacrynicum, etc.), psychotropic drugs (an imipramine, amitriptyline, Chlozepidum, diazepam, carbamazepine, etc.), antirheumatic means (indometacin, Butadionum, acetylsalicylic acid, Allopyrinolum, etc.) antiulcerous means (Tagametum, ranitidine), and also mercazolil, iodinated contrast mediums, etc.

Cholestatic forms of medicinal hepatitis are more often than an obusloalena aminazine and its derivatives, testosterone derivatives, hormones of a yellow body (oral contraceptives), Fosfestrolum, Ajmalinum, etc. In particular, oral contraceptives cause cholestasias with a frequency of 1:10 000 in Western Europe and the USA and 1:4000 in Chile and Scandinavia.

Due to a large number of oligosymptomatic forms of medicinal hepatitises at the patients receiving hepatotoxic drugs follows regularly (at least 1 time in 14 days) to investigate aminotransferases, GGTF (or an alkaline phosphatase) and blood serum bilirubin.

Issues of classification are differently resolved for different etiological forms of an acute hepatitis. Clinical classification of a viral hepatitis of Century is in this respect indicative.

Viral hepatitis In

1.0. Acute form
1.1.0. Asymptomatic form
1.2.0. Typiform
1.2.1. Anicteric
1.2.2. Icteric, including cholestatic
1.3.0. Fulminant (fulminantny) shape or acute (subacute) necrosis of a liver.
1.4.0. An atypical form (acute viral nephrite, a virus nodose periarteritis, a virus pseudorheumatism, a virus acute polyradiculoneuritis — Giyen's syndrome — Barret, viral aplastic anemia, etc.)

Acute alcoholic hepatitis in clinical forms is close to an acute viral hepatitis. Enters a component an alcoholic liver disease where include: a) alcoholic hepatomegalia; b) fatty dystrophy of a liver (simple steatosis); c) acute alcoholic hepatitis; d) fatty dystrophy with mesenchymal reaction (chronic alcoholic hepatitis); e) alcoholic cirrhosis.

Approximate formulation of the diagnosis:
1. An acute viral hepatitis In, a heavy current (the typiform and icteric option usually are not specified in the diagnosis — in these cases they are meant).
2. An acute viral hepatitis And In, a fulminant form.
3. Acute alcoholic hepatitis, severe form, edematous and ascitic option.
4. Acute medicinal (aymalinovy) hepatitis. Cholestatic option.

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