Chronic hepatitis: causes

Postponed acute viral hepatitis

The most common cause of chronic hepatitis is acute acute viral hepatitis. Currently, there is an opportunity to chronicle four of the seven forms of acute viral hepatitis - B, C, D, G.

Postponed acute viral hepatitis B

The transferred acute viral hepatitis B is one of the most frequent causes of chronic viral hepatitis.

According to WHO, there are up to 300 000 000 carriers of hepatitis B virus (HBV) in the world. According to research data, about 3 million people are infected with the hepatitis B virus in the Republic of Belarus. About 64,000 people are infected each year.

Acute viral hepatitis B passes into chronic viral hepatitis in about 5-10% of cases.

Criteria for the threat of transformation of acute viral hepatitis B into chronic:

• presence of concomitant delta infection;
• previous alcohol damage of the liver, suppression of the immune response in diseases of the liver, blood, diffuse connective tissue diseases, treatment with glycocorticoids;
• severe course of acute viral hepatitis B;
• prolonged course of acute viral hepatitis B (more than 3 months);
• early-evolving and persistent hypergammaglobulinemia;
• preservation in the blood of HBsAg for more than 60 days and HBeAg for more than 2 months, antibodies to the HBcAg IgM class for more than 45 days;
• high blood levels of HBV-DNA (determined by polymerase chain reaction);
• the presence in the blood of the CEC is more than 10 units;
• monotonously low concentrations of anti-HBe without a tendency to increase the titer;
• a steady decrease in the number of T-lymphocytes in the blood;
• presence of HLA B ₁₈, B ₃₅, B ₇ (predispose to HPV), B ₈ (predisposes to CAG);
• an increase in pre-SI antigen content and an increase in the pre-SIAg / HBsAg ratio (this criterion is especially important in patients with HBVe (-), ie infected with a mutant strain that has lost the ability to synthesize HBeAg).

Infection with hepatitis D virus, advanced acute hepatitis D

Hepatitis D virus (D-virus, delta virus) was discovered by Rizzett in 1977. Structurally, the D-virus is a 35-37 nm particle consisting of the outer membrane (lipids and HBsAg) and the inner part.

The internal part of the hepatitis D virus (HDV) consists of the genome and protein that codes for the synthesis of a specific antigen - HDAg. The genome is a circular single-stranded RNA of very small size. HDAg consists of two proteins with an amino acid chain of different lengths that regulate the rate of genome formation. A protein of smaller dimensions stimulates, and a larger protein inhibits the synthesis of the genome (genomic and antigenomic proteins).

There are three genotypes HDV - I, II, III. Among the genotype I, two subtypes, la and 1c, are distinguished. All genotypes belong to the same serotype, therefore antibodies formed to them are universal.

Replication of the hepatitis D virus occurs in the presence of the hepatitis B virus. HDV is inserted into the outer HBV envelope consisting of HBsAg. However, according to Smedile (1994), it is possible to develop HDV infection in the absence of HBsAg, since the lack of intrinsic polymerase in the virus is compensated by cellular (hepatocellular) polymerase.

The hepatitis D virus is localized in the nucleus of the hepatocyte.

Source of infection - patients with viral hepatitis B (acute or chronic), simultaneously infected with D.

The routes of transmission of D-infection are the same as hepatitis B:

• parenteral, transfusion of blood, its components;
• sexual;
• from mother to the fetus.

The last two routes of infection have a slightly lower value than with HBV infection.

Penetrating into the body, the D-virus enters the nucleus of the hepatocyte, becomes full and replicates only in the environment of HBsAg.

D-virus in contrast to the hepatitis B virus has a direct cytopathic effect on the hepatocyte.

This fact is probably the most important in the pathogenesis of chronic viral hepatitis D. Autoimmune mechanisms caused directly by the D-antigen are also of great importance. In addition, since it is present only together with the hepatitis B virus, pathogenesis also includes mechanisms for chronic hepatitis B infection.

In the case of D-virus attachment to chronic viral hepatitis B, its weighting is noted, the transition to HAT and liver cirrhosis are more frequent. When D-virus is attached to acute hepatitis B, its heavy, fulminant course and rapid transition to cirrhosis of the liver (HDV cirrhosis) are observed.

Endemic to the delta infection are Moldova, Turkmenistan, Uzbekistan, Kazakhstan, Central and South Africa, South America, South India, countries of the Middle East and the Mediterranean.

Infection with hepatitis C virus, advanced viral hepatitis C

Now the independence of the G virus is established; his role in the etiology of acute hepatitis, and even more so chronic hepatitis is now widely discussed. The hepatitis G virus is transmitted parenterally. It is an RNA-containing virus. In Europe and the US, hepatitis G virus infection occurs in patients with chronic hepatitis B (10% of cases), chronic hepatitis C (20%), alcoholic hepatitis (10%), and 20% hemophilia. Acute viral hepatitis G can be transformed into chronic hepatitis G, cirrhosis and, possibly, liver cancer.

Alcohol abuse

Alcohol abuse is one of the most important causes of chronic hepatitis. The pathogenesis of chronic alcoholic hepatitis is as follows:

• direct toxic and necrobiotic effects of alcohol on the liver;
• a very pronounced toxic effect on the liver metabolite alcohol acetaldehyde (it is 30 times more toxic than alcohol);
• a sharp activation under the influence of alcohol lipid peroxidation in the liver, the formation of free radicals, intensely damaging hepatocytes and lysosomal membranes, resulting in the release of lysosomalous enzymes that aggravate the damage of hepatocytes;
• the formation of alcoholic hyaline in hepatocytes and the development in response to it of the damaging immune cytotoxic reaction of T lymphocytes;
• inhibition of liver regeneration and stimulation of fibrosis;
• a common combination of alcohol abuse and hepatitis B or C virus mutually reinforces the pathogenetic effect of these factors.

[1], [2], [3], [4], [5], [6], [7]

Autoimmune reactions

Autoimmune reactions as the root cause of chronic hepatitis are recognized in the event that it is impossible to establish any other reasons. As a rule, there is an inborn deficiency of T-suppressor function of lymphocytes. In the pathogenesis of autoimmune hepatitis, the formation of autoantibodies to the component of hepatocytes with hepatic-specific lipoprotein, antinuclear antibodies and antibodies to smooth muscle is of primary importance. To the development of autoimmune hepatitis predisposes the presence of HLA-B ₈, DR ₃.

[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18],

Effect of hepatotropic drugs

Some drugs can cause chronic hepatitis.

Hepatotropic drugs are divided into two groups:

• true hepatotoxins;
• hepatotoxins idiosyncrasy.

The true hepatotoxins, in turn, are divided into two subgroups: direct and indirect hepatotoxic action.

By hepatotoxins direct hepatotoxic action include:

• paracetamol;
• salicylates (with the use of 2 g of salicylates per day, focal hepatocellular necrosis in 2/3 patients is possible;
• antimetabolites (methotrexate, 6-mercaptopurine);
• large doses of tetracycline (for the prevention of liver damage the daily dose should not exceed 2 g for plural admission and 1 g for intravenous administration);
• amiodarone (cordarone).

Hepatotoxic medications indirectly damage the liver by interfering with any metabolic process. Among this subgroup, cytotoxic (puromycin, tetracycline) is isolated; Cholestatic (anabolic steroid preparations, chlorpromazine, aminazine, chlorpropamide, propylthiouracil, novobiocin, etc.) drugs and carcinogens.

In the group of hepatotoxins idiosyncrasy, two subgroups are distinguished. The first subgroup includes medicinal substances that cause liver damage due to hypersensitivity reactions of delayed type, such as fluorotane; tranquilizers phenothiazines; anticonvulsants (diphenin, phenachemide); antidiabetic drugs (bucarban, chlorpropamide); antibiotics (oxacillin).

The second subgroup includes medicines that cause liver damage due to toxic metabolites formed during the biotransformation of drugs in the liver (acitamifen, isoniazid).

Medicines cause a variety of liver damage. They are classified as follows:

• Acute medicinal liver damage:
  • virus-like (cytolytic) acute hepatitis;
  • simple (canal) cholestasis;
  • Cholangiolytic (hepatoconjular) hepatitis;
  • phospholipidosis.
• Chronic liver disease:
  • chronic active hepatitis;
  • chronic persistent hepatitis;
  • chronic cholestasis;
  • fibrosis of the liver;
  • cirrhosis of the liver.
• Hepatovascular lesions:
  • veno-occlusive disease (Badd-Chiari syndrome);
  • Peliosis (cysts filled with blood and communicating with the sinusoids of the liver);
  • thrombosis of the hepatic vein.
• Tumors:
  • focal modular hyperplasia;
  • adenoma;
  • hepatocellular carcinoma;
  • angiosarcoma.

Chronic drug-induced hepatitis occurs in 9% of cases of medicinal hepatopathies and can be persistent and active.

Chronic persistent hepatitis can develop with oxyphenizate, methyldopa (dopegit, aldomet), isoniazid, acetylsalicylic acid, certain antibiotics, sulfonamides, oral contraceptives, with prolonged use of barbiturates, carbamazepine, phenylbutazone, allopurinol, diphenylhydantoin (diphenine), hydralazine, diazepam.

Chronic active hepatitis is described with long-term use of methotrexate, azathioprine, tetracycline, and its development may be due to the use of the above agents that cause chronic persistent hepatitis.

[19], [20], [21], [22], [23], [24], [25],

Genetically determined forms of chronic hepatitis

Genetically determined forms of chronic hepatitis (with hemochromatosis, Wilson-Konovalov's disease, a2-antitrypsin deficiency).