Chronic Hepatitis - Causes

Past acute viral hepatitis

The most common cause of chronic hepatitis is acute viral hepatitis. Currently, the possibility of chronicization of four of the seven forms of acute viral hepatitis - B, C, D, G - has been established.

Past acute viral hepatitis B

Past acute viral hepatitis B is one of the most common causes of chronic viral hepatitis.

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

Acute viral hepatitis B develops into chronic viral hepatitis in approximately 5-10% of cases.

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

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

Hepatitis D virus infection, acute hepatitis D

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

The internal part of the hepatitis D virus (HDV) consists of a genome and a protein encoding 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, regulating the rate of genome formation. The smaller protein stimulates, and the larger protein inhibits genome synthesis (genomic and antigenomic proteins).

There are three genotypes of HDV - I, II, III. Among genotype I, there are two subtypes - la and 1b. All genotypes belong to one serotype, so the antibodies formed against them are universal.

Replication of the hepatitis D virus occurs in the presence of the hepatitis B virus. HDV is embedded in the outer shell of HBV, which consists of HBsAg. However, according to Smedile (1994), HDV infection can develop in the absence of HBsAg, since the absence of the virus's own polymerase is compensated for by cellular (hepatocellular) polymerase.

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

The source of infection is patients with viral hepatitis B (acute or chronic), simultaneously infected with the D virus.

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

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

The last two routes of infection are somewhat less important than in HBV infection.

Having penetrated the body, the D-virus enters the hepatocyte nucleus, becomes complete and replicates only in the environment of HBsAg.

The D-virus, unlike 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, the mechanisms of chronicization of hepatitis B are also included in the pathogenesis.

In case of joining of D-virus to chronic viral hepatitis B, its aggravation is observed, transition to CAT and liver cirrhosis is more often observed. When joining D-virus to acute hepatitis B, its severe, fulminant course and rapid transition to liver cirrhosis (cirrhosis of HDV) are observed.

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

Hepatitis C virus infection, previous viral hepatitis C

At present, the independence of the G virus has been established; its role in the etiology of acute hepatitis, and especially chronic hepatitis, is now widely discussed. The hepatitis G virus is transmitted parenterally. It is an RNA-containing virus. In Europe and the USA, infection with the hepatitis G virus occurs in patients with chronic hepatitis B (in 10% of cases), chronic hepatitis C (in 20% of cases), alcoholic hepatitis (in 10% of cases), and in 20% of patients with hemophilia. Acute viral hepatitis G can transform into chronic hepatitis G, liver 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;
• very pronounced toxic effect on the liver of the alcohol metabolite acetaldehyde (it is 30 times more toxic than alcohol);
• sharp activation of lipid peroxidation in the liver under the influence of alcohol, the formation of free radicals that intensively damage hepatocytes and lysosomal membranes, as a result of which lysosomal enzymes are released, aggravating damage to hepatocytes;
• the formation of alcoholic hyaline in hepatocytes and the development of a damaging immune cytotoxic reaction of T-lymphocytes in response to it;
• inhibition of liver regeneration and stimulation of fibrosis formation;
• The frequent combination of alcohol abuse and hepatitis B or C virus mutually enhances the pathogenetic effect of these factors.

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Autoimmune reactions

Autoimmune reactions as the primary cause of chronic hepatitis are recognized in cases where it is impossible to establish any other causes. As a rule, there is a congenital deficiency of the T-suppressor function of lymphocytes. In the pathogenesis of autoimmune hepatitis, the formation of autoantibodies to the hepatocyte component liver-specific lipoprotein, antinuclear antibodies and antibodies to smooth muscles is of primary importance. The presence of HLA-B ₈, DR ₃ predisposes to the development of autoimmune hepatitis.

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Effect of hepatotropic drugs

Some medications can cause chronic hepatitis.

Hepatotropic drugs are usually divided into two groups:

• true hepatotoxins;
• idiosyncratic hepatotoxins.

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

Hepatotoxins with direct hepatotoxic action include:

• paracetamol;
• salicylates (with the use of 2 g of salicylates per day, focal hepatocellular necrosis may develop in 2/3 of patients;
• antimetabolites (methotrexate, 6-mercaptopurine);
• large doses of tetracycline (to prevent liver damage, the daily dose should not exceed 2 g when taken orally and 1 g when administered intravenously);
• amiodarone (cordarone).

Indirect hepatotoxin drugs damage the liver by interfering with some metabolic process. This subgroup includes cytotoxic (puromycin, tetracycline); cholestatic (anabolic steroid drugs, chlorpromazine, aminazine, chlorpropamide, propylthiouracil, novobiocin, etc.) drugs and carcinogens.

In the group of idiosyncratic hepatotoxins, two subgroups are distinguished. The first subgroup includes medicinal substances that cause liver damage due to allergic reactions of the delayed-type hypersensitivity type - these are fluorothane; phenothiazine tranquilizers; anticonvulsants (diphenin, phenacemide); antidiabetic agents (bucarban, chlorpropamide); antibiotics (oxacillin).

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

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

• Acute drug-induced liver injury:
  • virus-like (cytolytic) acute hepatitis;
  • simple (canalicular) cholestasis;
  • cholangiolytic (hepatocanalicular) hepatitis;
  • phospholipidosis.
• Chronic drug-induced liver damage:
  • chronic active hepatitis;
  • chronic persistent hepatitis;
  • chronic cholestasis;
  • liver fibrosis;
  • cirrhosis.
• Hepatovascular lesions:
  • veno-occlusive disease (Budd-Chiari syndrome);
  • peliosis (cysts filled with blood and communicating with the liver sinusoids);
  • hepatic vein thrombosis.
• Tumors:
  • focal modular hyperplasia;
  • adenoma;
  • hepatocellular carcinoma;
  • angiosarcoma.

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

Chronic persistent hepatitis can develop with the use of oxyphenisatin, methyldopa (dopegyt, aldomet), isoniazid, acetylsalicylic acid, some antibiotics, sulfonamides, oral contraceptives, with long-term use of barbiturates, carbamazepine, phenylbutazone, allopurinol, diphenylhydantoin (diphenin), hydralazine, diazepam.

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

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Genetically determined forms of chronic hepatitis

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