Chronic hepatitis C: causes

The cause of chronic hepatitis C - hepatitis C virus (HCV) is a small virus, 30-38 nm in size, has a shell and an inner part - the core. The envelope contains glycoproteins E1 and E2, NS1. The inner part contains the genome of the virus - a long single-stranded linear RNA and a protein C-antigen (C-co-protein).

The genome of the virus has sites that encode the synthesis of structural and non-structural proteins. Structural proteins include core C-protein and envelope glycoproteins E1, E2. Non-structural proteins include enzymes that play a role in viral replication, RNA-dependent RNA polymerase, NS2, NS4, NS3-helicase (metalloproteinase) proteins. A key role in the replication of virus C belongs to NS3-proteinase, an enzyme that catalyzes the final stage of the synthesis of the viral polyprotein. To each of the structural and non-structural proteins, antibodies circulating in the blood are produced. These antibodies do not possess virus neutralizing properties.

There are 6 genotypes of the hepatitis C virus, the classification of which is based on the analysis of the 5'-terminal portion of the unstructured NS5 region (genotypes la, lb, 1c, 2a, 2b, 2c, 3a, 3b, 4, 5, 6).

In North Africa, 4, in North and South-East Asia and the Far East - 1, 2, 6, in the US - 1 genotype.

The world has more than 500 million carriers of hepatitis C virus. Genotype 1b is associated with a more severe course of the disease, a higher content of HCV RNA in the blood serum, a worse response to antiviral medications and a greater likelihood of a serious recurrence of hepatitis C after liver transplantation. Genotype 4 is associated with a poor response to interferon therapy.

Chronic HCV infection usually begins in a mild form, but in 50% of patients within 10 years the disease progresses, 10-20% develop cirrhosis of the liver, less often liver cancer.

The hepatitis C virus is an RNA virus. Serum markers of the hepatitis C virus are the virus RNA and antibodies to HCV (HCVAb).

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How is hepatitis C transmitted?

Chronic hepatitis C is transmitted in several ways:

• parenteral, especially transfusion (transfusion of blood, its components - cryoprecipitate, fibrinogen, factors VIII and IX, parenteral administration of various drugs, hemodialysis); HCV is the main cause of post-transfusion hepatitis (85-95% of all cases);
• the sexual way;
• from the mother to the fetus (through the placenta).

Histological manifestations of chronic hepatitis C vary from CPG to CAG with or without cirrhosis of the liver. The spread of hepatitis C largely depends on environmental factors.

There are 2 main mechanisms of hepatitis C virus damage to the liver:

• direct cytopathic (cytotoxic) effect of the virus Sleep hepatocytes;
• immuno-mediated liver damage, in favor of which there is evidence that viral hepatitis C may be associated with autoimmune diseases (Sjogren's syndrome, cryoglobulinemia, etc.), as well as the detection in liver biopsy specimens of patients with hepatitis C virus lymphoid cell infiltration, consisting of B- and T-lymphocytes.

Markers of the hepatitis C virus are detected among medical staff of hematological departments in 12.8%, in patients with blood diseases - in 22.6%, in patients with chronic hepatitis - in 31.8%, in patients with cirrhosis of the liver - in 35.1% of cases, among the population of Russia - in 1.5- 5% of the population.

Immunity in hepatitis C is not optimal (it is called suboptimal), which does not provide reliable control over the infectious process. Therefore, acute viral hepatitis C so often transformed into a chronic, the same is explained and frequent reinfection with the virus C. The hepatitis C virus "slips" from under immunological surveillance. This is explained by the unique ability of the hepatitis C virus to constantly change the antigenic structure, repeatedly updated for even one minute. Such a constant variability of the hepatitis C virus leads to 10 ^10-11 antigenic variants of HCV appearing within a day , which are close, but still immunologically different. In such a situation, the immunity system does not have time to continuously recognize newer and newer antigens and continuously produce antibodies neutralizing them. In the structure of HCV, the maximum variability is noted in envelope antigens, the protein C of the core varies little.

The course of HCV infection stretches for many years (by the type of slow viral infection). Clinically pronounced chronic hepatitis develops on average through 14, cirrhosis - through 18, hepatocarcinoma - in 23-18 years.

A distinctive feature of acute viral hepatitis C is a torpid, latent or mildly symptomatic course, which for a long time remains unrecognized, but progressively progresses, and subsequently rapidly leads to the development of liver cirrhosis with hepatocellular carcinoma (hepatitis C virus is a "gentle killer").

The markers for the HCV replication phase are the detection of anti-HCVcoreIgM and IgG in the blood with an anti-HCV1gG / IgM coefficient within 3-4 AU in the absence of aHTH-HCVNS4 and detection of HCV-RNA in the blood.

The hepatitis C virus can replicate and extra-hepatic, including in monocytes.

Mechanisms of liver damage in chronic hepatitis C

It is believed that the virus has a direct cytopathic effect. This action is different from the damage caused by HBV, which is considered immune. There is growing evidence that the immune mechanisms play a part in chronicizing HCV infection.

Cytotoxic flaviviruses tend to cause direct hepatocellular damage without pronounced inflammation. In chronic HCV infection, histological examination of the liver reveals minimal damage, despite progression. Lymphocyte reaction is poorly expressed, eosinophilia of cytoplasm of hepatocytes is noted. In contrast to chronic hepatitis B, treatment of chronic HCV infection with IFN is accompanied by a rapid decrease in ALT activity and HCV-RNA concentration.

There is a correlation between the severity of the disease and the level of viremia. Very high levels of viremia and severe liver damage are observed in patients with chronic HCV infection after liver transplantation.

The immune response to HCV is weak, as evidenced by an increase in ALT activity, which is accompanied by an increase in the HCV-RNA titers. With the inoculation of a significant number of viral particles (blood transfusions), the liver disease is more severe than with a less massive ingestion of viruses into the body (intravenous drug use).

In media HCV noted persistent HCV-viremia without clinically delineated liver disease. Correlation between the content of HCV-RNA in liver tissue and histological activity is absent.

Immunosuppressive therapy reduces the activity of serum transaminases, although viremia increases.

The results of immunoelectron microscopy suggest that intralobular cytotoxic T cells support liver damage. Cytotoxic lymphocytes recognize epitopes of the core and the protein coat of HCV. Studies in vitro autologous gepatotsitotoksichnosti convincingly demonstrated that HLA-restrictive 1 CD8 ⁺ T-cell toxicity is an important pathogenetic mechanism in chronic the HCV-infection.

Serological tests for autoantibodies (antinuclear, smooth muscle and rheumatoid factor) are positive. However, these autoantibodies do not affect the severity of the disease and have no pathogenetic significance.

Evidence of hepatic cytotoxicity in chronic HCV infection has been obtained. The immune response to HCV is also clearly documented, but its role as a protective factor and as a factor responsible for chronic infection remains unclear.