Chronic hepatitis: classification

In 1968 De Groot et al. In the journal Lancet published a classification of chronic hepatitis, which was approved by the European Association for the Study of the liver. The classification is based on the isolation of morphological variants of chronic hepatitis. The authors proposed to distinguish the following morphological variants of chronic hepatitis.

1. Chronic persistent hepatitis - characterized by severe infiltration of lymphoid cells of portal fields (portal hepatitis). These infiltrates do not penetrate the hepatic lobule, they do not cause damage to the integrity of the border plate (the layer of hepatocytes separating the portal field from the hepatic lobe). In hepatocytes, dystrophic changes can occur. Possible proliferation of Kupffer cells, the development of portal fibrosis.
2. Chronic aggressive hepatitis (hereinafter, the term aggressive was replaced by active hepatitis from deontological considerations).

With this variant of chronic hepatitis, the inflammatory infiltrate seizes the portal tracts and further, destroying the border plate, invades the hepatic lobule, an inflammatory reaction from moderate to severe is noted. Depending on this in the subsequent began to allocate chronic hepatitis with moderate and pronounced activity.

In chronic hepatitis with moderate activity, staged small-focal necrosis of hepatocytes in the parenchyma adjacent to portal fields is characteristic. As a rule, inflammatory infiltrates and step necrosis penetrate no more than the middle of the lobules.

In chronic hepatitis with pronounced activity, multilobular, bridge-like portocentral (connecting portal fields with the central zone of the hepatocyte) and port-portal necroses (connecting adjacent portal fields) develop. All preconditions are created for the violation of the architectonics of the lobules of the liver and the development of cirrhosis in the future.

Later, many authors identified the so-called necrotizing form of chronic hepatitis.

In 1971, Popper and Allaharden showed the existence of a lobular form of chronic hepatitis. It is characterized by small necrosis in the second or third zone of the acini and intralobular lymph-cellular infiltration, which is much more pronounced than the infiltration of the portal tracts (the pronounced dominance of intra-lobular lesions over the portal and periportal lesions).

In 1974, the international classification of chronic liver diseases was adopted in Acapulco (Mexico). This classification retains the same morphological principle of separation of chronic hepatitis into persistent and active. However, it was argued that the etiology of chronic hepatitis is a transferred acute viral hepatitis B or A, other etiological factors were considered unproven.

In 1994, the World Congress of Gastroenterologists in Los Angeles adopted the recommendations of the International Working Group on the new nomenclature and terminology of chronic hepatitis and cirrhosis of the liver. It is recommended to include the etiological component in the diagnosis of chronic hepatitis and cirrhosis of the liver in all possible cases.

Nomenclature and definition of chronic hepatitis
(World Congress of Gastroenterologists, Los Angeles, 1994)

1. Chronic hepatitis B is an inflammatory liver disease caused by the hepatitis B virus (HBV), lasting 6 months or more and capable of leading to cirrhosis or being associated with cirrhosis.

The expression to be associated with cirrhosis most likely means the following possibilities:

• chronic hepatitis B joins already existing cirrhosis of another etiology;
• chronic hepatitis B proceeds in parallel with cirrhosis of the same name and determines the degree of activity of the process.

2. Chronic hepatitis D is an inflammatory liver disease caused by hepatitis D virus (HDV) in combination with HBV infection lasting 6 months or more and capable of leading to cirrhosis or to be associated with cirrhosis.
3. Chronic hepatitis C is an inflammatory liver disease caused by the hepatitis C virus, lasting 6 months or more and capable of leading to cirrhosis or being associated with cirrhosis.
4. Chronic viral hepatitis, not otherwise characterized - an inflammatory disease of the liver, lasting 6 months or more and caused by an unidentified or unknown virus.
5. Autoimmune hepatitis is an intractable, predominantly periportal hepatitis (usually with hypergamma-globulinemia and tissue autoantibodies), which in most cases is susceptible to immunosuppressive therapy.
6. Chronic hepatitis, not classified as viral or as an autoimmune inflammatory disease of the liver, lasting 6 months or more, which has the features of viral and / or autoimmune hepatitis, but it is impossible to clearly establish a viral or autoimmune etiologic factor.
7. Chronic medicinal hepatitis is an inflammatory disease of the liver that lasts for 6 months or more due to the side effect of the drug. The side effect of the drug may lie:

• direct toxic effect of the drug or its metabolites;
• reaction idiosyncrasy to the drug or its metabolite.

8. Disease of a2-antitrypsin deficiency of the liver is a chronic liver disease associated with or caused by an autosomal recessive disorder of protein metabolism, which occurs in typical cases with abnormally low values of serum a-antitrypsin (serum a-protease inhibitor). Liver disease can lead to chronic hepatitis or cirrhosis of the liver or be associated with these complications.
9. Primary biliary cirrhosis.
10. Primary sclerosing cholangitis.
11. Disease of the liver of Wilson-Konovalov.

Terms that are obsolete and that are not appropriate to use are:

• chronic persistent hepatitis;
• chronic active hepatitis;
• chronic non-parasitic destructive cholangitis;
• pericholangitis;
• portal cirrhosis of the liver;
• postnecrotic cirrhosis of the liver;
• post-hepatitis cirrhosis;
• Laennec's cirrhosis;
• Nigricative cirrhosis.

Recommendations not to use the terms chronic persistent hepatitis, chronic active hepatitis and chronic lobular hepatitis are explained by the fact that these categories essentially represent a system for assessing the degree of activity of the inflammatory process in the liver. Morphological variants of chronic hepatitis correlate with its degree of activity.

Desmet, Gerber, Hoofiiagle.Manus, Schneuer in 1995 proposed the classification of chronic hepatitis, which, in their opinion, allows the realization of all available clinical, etiological and histological information. The classification is divided into three main sections: the etiology, the degree of activity and the stage of the disease.

The authors distinguish the following etiological forms of chronic hepatitis: chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, autoimmune hepatitis (types 1, 2, 3), drug-induced chronic hepatitis, chronic hepatitis of unknown etiology (cryptogenic hepatitis ).

The degree of activity of chronic hepatitis is determined by the severity, severity and depth of the necrotic and inflammatory processes.

To determine the degree of activity of chronic hepatitis, the authors suggest using the histological index Knodell (HAI-index).

Etiology of chronic hepatitis

• Chronic hepatitis B
• Chronic hepatitis D
• Chronic hepatitis E
• Chronic hepatitis G
• Autoimmune Hepatitis
  • type 1
  • type 2
  • type 3
• Drug-induced hepatitis
• Cryptogenic hepatitis

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

The components of the histological activity index (Knodell, 1981)

Components	Digital Score Range
1. Periportal necrosis with or without bridged necrosis	0-10
2. Intralobular degeneration and focal necrosis	0-4
3. Portal necrosis	0-4
4. Fibrosis	0-4

Note:

1. The degree of activity reflects the first three components, the fourth - the stage of the process.
2. The histological activity index is obtained by summing up the digits for the first three components.

Depending on the histological index, it is possible to distinguish 4 levels of activity: minimal, mild, moderate, severe and to correlate with forms of chronic hepatitis according to old terminology.

To assess the degree of activity of chronic hepatitis, the blood level of the ALT and clinical data are also used.

• Soft process flow - ALAT activity is less than 3 norms.
• Moderate flow - ALT activity from 3 to 10 norms.
• Heavy current - more than 10 norms.

The clinical course is assessed on the basis of three main methods:

• use of a questionnaire with a list of symptoms (fatigue, nausea, abdominal pain, poor appetite), the patient indicates the degree of influence of these symptoms on him: does not influence (0) or affects slightly (1), moderately (2), quite significantly (3), extremely (4);
• use of a long analogue scale 10 cm long, graduated from "absent" to "more severe condition I did not experience", on which the patient makes a mark at a point corresponding to the severity of each symptom;
• The use of the Karnofsky scale, by which patients are asked to regulate their symptoms depending on how they cope with the problems of daily life, i.e. The influence of the symptoms of the disease on the quality of life is assessed.

Stages of chronic hepatitis

The stages of chronic hepatitis are isolated on the basis of the severity and prevalence of fibrosis and the development of cirrhosis. In chronic hepatitis, fibrous tissue is formed inside and around the portal tracts, combined with a periportal necro-inflammatory process. Stepwise necrosis can spread to the adjacent portal tracts (port-portal septums) or penetrate the hepatic lobes and reach the central hepatic veins (port-central septa).

Cirrhosis of the liver is characterized by parenchymal nodules of regeneration, surrounded by fibrotic septa, which leads to a violation of architectonics, a violation of blood flow and portal hypertension.

Thus, taking into account the above recommendations of the World Congress of Gastroenterologists in Los Angeles (1994), the proposals of Desmet et al. (1995), the current classification of chronic hepatitis can be presented in the following form:

Serological markers and variants of chronic hepatitis

Chronic hepatitis B

• The replication phase (HBeAg-positive chronic hepatitis) - serological markers: HBeAg, HBcAbIgM. Pre-S antigens, DNA polymerase, DNA-HBV
• Integration phase (НВеAg-negative chronic hepatitis) - serological markers: HBsAg, HBcAblgG, HBeAb
• HBeAg-negative chronic hepatitis with preserved viral replication (mutant HBVe variant) - serological markers: DNA
  polymerase, DNA-HBV, HBcAidM, pre-S, HBeAb antigens

Chronic hepatitis D

• Serological markers of the replication phase. HDV-RNA, antibodies to the D-antigen IgM and IgG

Chronic hepatitis C

• Serological markers of the replication phase: HCV-PHK, HCVcoreAblgM and IgG

Chronic hepatitis G

• HGV-RKK

Autoimmune hepatitis (type 1)

• Antibodies to nuclear antigens or to smooth muscles

Autoimmune hepatitis (type 2)

• Antibodies to type I hepatic-renal microsomes directed against cytochrome P-450 11 D6

Autoimmune hepatitis (type 3)

• Antibodies to solubilized hepatic antigen

Drug-induced hepatitis

• In a number of cases, antinuclear antibodies and antibodies to hepatic-renal microsomes

Degree of activity of chronic hepatitis

• Chronic hepatitis with minimal activity
• Low-grade chronic hepatitis
• Moderate chronic hepatitis
• Severe chronic hepatitis

[8], [9], [10]

Degree (stage) of fibrosis

• No fibrosis
• Slightly pronounced
• Moderate fibrosis
• Severe fibrosis
• Cirrhosis of the liver

[11], [12], [13],