Autoimmune hepatitis is a chronic necrotic-inflammatory liver disease of unknown etiology in which the main target of the immune response is hepatocyte and characterized by a periportal or more extensive inflammatory process in the liver, the presence of hypergammaglobulinemia and the appearance of a wide range of autoantibodies.
Pathogenesis. Autoimmune hepatitis is the response of a genetically predisposed organism to some external agent, which is a starting point in the development of autoimmune processes that cause progressive inflammatory necrotic changes leading to fibrosis and cirrhosis of the liver. The central link in the pathogenesis of autoimmune hepatitis is the defect of immunoregulation – (!) Loss of tolerance to its own antigens. Under the influence of resolving factors, this leads to the appearance of “forbidden” clones of lymphocytes sensitized to autoantigens of the liver and carrying out damage to the hepatocytes.
In the development of the disease is important a combination of several factors that are in a particular combination.
Genetic predisposition: most patients with autoimmune hepatitis have been shown to have a phenotype for the main histocompatibility complex antigens: HLA-A1, HLA-B8, HLA-DR4, DR3, DR52a, C4AQ0 and others. A significant role in the occurrence of autoimmune hepatitis is played by the “autoimmune hepatitis”. transcription factor “, the so-called” type 1 autoimmune regulator “.
The starting agent is not yet known, but there is some evidence of the role of the hepatitis viruses, measles, Epstein-Barr viruses, hepatitis A, B, C, D, G viruses, interferon herpes simplex virus as initiators of the onset of autoimmune hepatitis.
Pathomorphology of autoimmune hepatitis . Necrosis in the periportal and septal zones or lobular hepatitis are characteristic. Portal tracts of the liver on biopsy specimens are expanded with the accumulation in them of extensive infiltrates having different cellular composition: lymphocytes, macrophages, plasma cells. Lobular hepatitis – lobular hepatitis, necrosis is detected in the second and third zones of the acini, and intralobular lymphoid cell infiltration is detected, which is much more pronounced than the infiltration of portal tracts. (!)
Lobular hepatitis is part of the histological picture of autoimmune hepatitis in the event that it is detected simultaneously with periportal hepatitis. On autoimmune hepatitis may indicate, in addition to the above, the presence of multicore hepatocytes. The pattern of fibrosis may be present (to some degree or another) even with a moderate degree of autoimmune hepatitis activity, and in advanced cases, especially in the absence of effective therapy, bridged necrosis and, eventually, liver cirrhosis is formed.
The clinical picture of autoimmune hepatitis. The clinical manifestations of autoimmune hepatitis are very diverse. On the one hand, there are asymptomatic forms, when an increase in ALT, AST is accidentally detected, and on the other, an acute onset of the disease with a severe course up to the development of fulminant hepatitis. Often the disease begins with asthenovegetative manifestations, pain in the area of the right precutum, and minor jaundice.
However, in most patients with autoimmune hepatitis, the onset of the disease is acute, as in acute viral hepatitis, and when the patient is examined, the doctor reveals signs such as: telangiectasia, palmar erythema, an increase in the liver and spleen, changes in blood tests (hypergamma globulinemia, an increase in IgG, a decrease in total protein, a sharp increase in ESR). Leukopenia and thrombocytopenia are observed in patients with advanced stages of the disease or with developed hypersplenism and portal hypertension syndrome. Jaundice in patients with autoimmune hepatitis can be of varying severity, often appears in the late stages of the disease, is intermittent, and increases in the period of exacerbations.
For autoimmune hepatitis is characterized by skin lesions in the form of a hemorrhagic rash, leaving behind pigmentation. Other symptoms include lupus erythema nodosum, focal scleroderma, palmar erythema and telangiectasia. All patients revealed changes in the endocrine system: amenorrhea, acne, hirsutism, stria. The diagnostic value of individual symptoms of the disease in autoimmune hepatitis is not the same. The most significant are prolonged fever and arthalgia.
Sometimes atoimmunny hepatitis begins with fever with extrahepatic manifestations of which may be mentioned autoimmune thyroiditis, ulcerative colitis, hyperthyroidism, hemolytic anemia, idiopathic thrombocytopenia, diabetes mellitus, celiac disease, polymyositis, fibrosing alveolitis, glomerulonephritis. Often autoimmune hepatitis is accompanied by infertility.
Also, autoimmune hepatitis is characterized by the detection of autoantibodies to the cellular and subcellular structures of cells of various organs: antibodies to cell nuclei (ANA is a typical marker of autoimmune hepatitis); antibodies to smooth muscle cells (SMA), antibodies to microsomes of liver cells and kidney kidney epithelial cells (LKM), antibodies to soluble hepatic antigen (SLA), antibodies to hepatocyte membrane antigens (LMA).
Depending on the identified autoantibodies, three types of autoimmune hepatitis are distinguished: type 1 – presence of ANA and SMA, anti-actin antibodies; Type 2 – the presence of LKM-1 (antibodies to the antigen microsomes of the liver and kidney type 1); Type 3 – the presence of SLA in the absence of ANA, SMA, LKM-1.
Autoimmune hepatitis is characterized (!) By a continuously progressive course, without spontaneous remissions. (!) Improvement of well-being are short-term, normalization of biochemical processes does not occur. The prognosis of autoimmune hepatitis is worse in patients with acute onset of the disease according to the type of acute viral hepatitis, with signs of cholestasis, ascites, and repeated episodes of acute hepatic encephalopathy. As a rule, patients who survived a critical period have a better prognosis.
It should be remembered that autoimmune hepatitis can occur (!) Not in its classical form, but atypically: patients also have (1) signs of an autoimmune process, but in general they (2) do not meet the criteria for an accurate or probable diagnosis of autoimmune hepatitis – they can simultaneously there are signs of both autoimmune hepatitis and other chronic liver diseases (mixed syndromes: autoimmune hepatitis and primary biliary cirrhosis, autoimmune hepatitis and primary sclerosing cholangitis), or signs that do not allow the diagnosis of autoimmune hepatitis according to criteria formed by international expert groups (separate syndromes: autoimmune cholangitis, chronic idiopathic hepatitis).
Diagnosis. For the diagnosis of autoimmune hepatitis, certain laboratory and histological features are necessary; lack of serum markers of viral infections; denial of alcohol abuse; lack of indications of blood transfusion or the use of a history of hepatotoxic drugs; presence of hypergammaglobulinemia. Histological changes (see above) in autoimmune hepatitis can include lobular hepatitis, if it is combined with periportal hepatitis, whereas (!) Lesions of the bile ducts, copper deposits and other changes indicating a different etiology of lobular hepatitis exclude the diagnosis of autoimmune hepatitis A. Diagnosis requires high titer (at least 1:80 in adult patients and 1:20 in children) antinuclear antibodies (ANA), antibodies to smooth muscle cells (SMA), or antibodies to liver microsomes or kidneys of type 1 ( LKM-1).
To diagnose atypical forms, it is important to identify their similarities with autoimmune hepatitis. Atypical varieties of autoimmune hepatitis usually occur sluggishly, they (!) Are characterized by non-specific symptoms, in particular fatigue, joint and muscle pain. Typical for hepatitis biochemical changes are combined with laboratory indicators characteristic of cholestasis, or prevail over them; severe pruritus, xanthelasma and hyperpigmentation are rare. (!) Atypical forms occur at any age in both sexes, but more often in women under 40 years of age. Histological examination identifies signs of periportal hepatitis in combination with or without lobular hepatitis characteristic of autoimmune hepatitis, but at the same time uncharacteristic morphological changes are often observed: bile duct damage, steatosis (fatty degeneration) and portal accumulation of lymphoid cells. Liver biopsy (!) Has no independent diagnostic value for atypical forms of autoimmune hepatitis. Liver biopsy reveals deviations from the norm, which should be considered only taking into account the relevant clinical picture. To date, none of the atypical forms of autoimmune hepatitis has been identified as an independent nosological unit.
Treatment . The basis of treatment is the prescription of prednisolone (which is also the drug of choice for starting treatment with atypical variants of autoimmune hepatitis). The response to this therapy is one of the criteria for the diagnosis of “autoimmune hepatitis.” Treatment with prednisone should be prescribed (!) To all patients with autoimmune high-activity hepatitis with fibrosis and cirrhosis or without. Usually, the initial dose of prednisone is 20-30 mg / day, followed by a gradual reduction to maintenance (usually 10 mg / day). Daily intake is preferred once in the morning. In patients with a moderate degree of disease activity, the administration of prednisone is often determined by the presence of complaints and symptoms of the disease. Patients without symptoms and with a moderate degree of activity of the process on the histological picture do not need treatment, but should be regularly observed to (!) Timely identify signs of disease progression. The combination of prednisolone with azathioprine can reduce side effects (a small dose of prednisone is required ). It is better to give 10 mg / day of prednisone with 50 mg / day of azathioprine than one prednisone, but in larger doses of e. Azathioprine itself is not able to induce remission, but its addition to prednisone supports it even at a dose of 1 mg / kg / day. With the ineffectiveness of treatment with azathioprine, 6-mercaptopurine is prescribed.