Autoimmune hepatitis is a progressive chronic inflammation of the liver, occurring with signs of a periportal or more extensive lesion and the presence of autoantibodies to liver cells. Clinical manifestations include asthenovegetative disorders, jaundice, pain in the right hypochondrium, skin rashes, hepatomegaly and splenomegaly, amenorrhea in women, gynecomastia in men. Diagnosis is based on serological detection of antinuclear antibodies (ANA), tissue antibodies to smooth muscle (SMA), antibodies to liver and kidney microsomes, etc., hypergammaglobulinemia, increased IgG titer, as well as liver biopsy data. The basis of treatment is immunosuppressive therapy with glucocorticosteroids.
In the structure of chronic hepatitis in modern gastroenterology, autoimmune liver damage accounts for 10-20% of cases in adults and 2% in children. Women get this disease 8 times more often than men. The first age peak of morbidity occurs before the age of 30, the second – during the postmenopausal period. The course of this pathology is rapidly progressive, in which cirrhosis of the liver, portal hypertension and liver failure develop quite early, leading to the death of patients.
Causes of autoimmune hepatitis
The etiology of autoimmune hepatitis has not been sufficiently studied. It is believed that the basis for the development of autoimmune hepatitis is the coupling with certain antigens of the main histocompatibility complex (human HLA) – the DR3 or DR4 alleles, detected in 80-85% of patients. Suspected trigger factors triggering autoimmune reactions in genetically predisposed individuals may be Epstein–Barr virus, hepatitis (A, B, C), measles, herpes (HSV-1 and HHV-6), as well as some medications (for example, interferon). More than a third of patients have other autoimmune syndromes – thyroiditis, Graves’ disease, synovitis, ulcerative colitis, Sjogren’s disease, etc.
The basis of the pathogenesis of autoimmune hepatitis is a deficiency of immunoregulation: a decrease in the subpopulation of T-suppressor lymphocytes, which leads to uncontrolled synthesis of IgG by B cells and destruction of the membranes of liver cells – hepatocytes, the appearance of characteristic serum antibodies (ANA, SMA, anti–LKM-l).
Depending on the antibodies formed, autoimmune hepatitis I (anti-ANA, anti-SMA positive), II (anti-LKM-l positive) and III (anti-SLA positive) types are distinguished. Each of the identified types of the disease is characterized by a peculiar serological profile, features of the course, response to immunosuppressive therapy and prognosis.
- Type I. It proceeds with the formation and circulation of antinuclear antibodies (ANA) in the blood – in 70-80% of patients; anti-smooth muscle antibodies (SMA) in 50-70% of patients; antibodies to neutrophil cytoplasm (pANCA). Disease type I develops more often at the age of 10 to 20 years and after 50 years. It is characterized by a good response to immunosuppressive therapy, the possibility of achieving stable remission in 20% of cases even after the withdrawal of corticosteroids. In the absence of treatment for 3 years, cirrhosis of the liver is formed.
- Type II. Antibodies to type 1 liver and kidney microsomes (anti-LKM-l) are present in the blood of 100% of patients. This form of the disease develops in 10-15% of cases of autoimmune hepatitis, mainly in childhood and is characterized by high biochemical activity. Type II is more resistant to immunosuppression; when drugs are discontinued, relapse often occurs; cirrhosis of the liver develops 2 times more often than with type I.
- Type III. Antibodies to soluble hepatic and hepatic-pancreatic antigen (anti-SLA and anti-LP) are formed. Quite often, this type of ASMA, rheumatoid factor, antimitochondrial antibodies (AMA), antibodies to liver membrane antigens (antiLMA) are detected.
Variants of atypical autoimmune hepatitis include cross-syndromes, which also include signs of primary biliary cirrhosis, primary sclerosing cholangitis, and chronic viral hepatitis.
Symptoms of autoimmune hepatitis
In most cases, pathology manifests suddenly and in clinical manifestations does not differ from acute hepatitis. Initially, it proceeds with pronounced weakness, lack of appetite, intense jaundice, the appearance of dark urine. Then, within a few months, an autoimmune hepatitis clinic unfolds. Less often, the onset of the disease is gradual; in this case, asthenovegetative disorders, malaise, severity and pain in the right hypochondrium, minor jaundice prevail. In some patients, autoimmune hepatitis begins with fever and extrahepatic manifestations.
The period of developed symptoms of autoimmune hepatitis includes pronounced weakness, a feeling of heaviness and pain in the right hypochondrium, nausea, itching, lymphadenopathy. Autoimmune hepatitis is characterized by unstable jaundice, which increases during periods of exacerbations, enlarged liver (hepatomegaly) and spleen (splenomegaly). A third of women with autoimmune hepatitis develop amenorrhea, hirsutism; boys may experience gynecomastia. Typical skin reactions are: capillaritis, palmar and lupus-like erythema, purpura, acne, telangiectasia on the skin of the face, neck and hands. During periods of exacerbations of disease, transient ascites may occur.
Systemic manifestations of autoimmune hepatitis include recurrent migrating polyarthritis, which affects large joints, but does not lead to their deformation. Quite often, disease occurs in combination with ulcerative colitis, myocarditis, pleurisy, pericarditis, glomerulonephritis, thyroiditis, vitiligo, insulin-dependent diabetes mellitus, iridocyclitis, Sjogren’s syndrome, Cushing’s syndrome, fibrosing alveolitis, hemolytic anemia.
Autoimmune hepatitis is diagnosed during a consultation with a hepatologist or gastroenterologist. The criteria of pathology are serological, biochemical and histological markers. According to international criteria, autoimmune hepatitis can be considered if:
- there is no history of hemotransfusion, taking hepatotoxic drugs, alcohol abuse;
- markers of active viral infection (hepatitis A, B, C, etc.) are not detected in the blood;
- the level of γ-globulins and IgG exceeds normal values by 1.5 or more times;
- significantly increased activity of AsT, AlT;
- antibody titers (SMA, ANA and LKM-1) for adults above 1:80; for children above 1:20.
A liver biopsy with a morphological examination of a tissue sample reveals a picture of chronic hepatitis with signs of pronounced activity. Histological signs of autoimmune hepatitis are bridged or stepped necrosis of the parenchyma, lymphoid infiltration with an abundance of plasma cells. Instrumental studies (ultrasound of the liver, MRI of the liver, etc.) in this disease do not have an independent diagnostic value.
Autoimmune hepatitis treatment
Pathogenetic therapy of the disease consists in immunosuppressive therapy with glucocorticosteroids. This approach makes it possible to reduce the activity of pathological processes in the liver: increase the activity of T-suppressors, reduce the intensity of autoimmune reactions that destroy hepatocytes.
Usually immunosuppressive therapy for autoimmune hepatitis is carried out with prednisone or methylprednisolone at an initial daily dose of 60 mg (1st week), 40 mg (2nd week), 30 mg (3-4 weeks) with a reduction to 20 mg as a maintenance dose. The reduction of the daily dosage is carried out slowly, taking into account the activity of the clinical course and the level of serum markers. The patient should take a maintenance dose until complete normalization of clinical, laboratory and histological parameters. Treatment of autoimmune hepatitis can last from 6 months to 2 years, and sometimes throughout life.
If monotherapy is ineffective, it is possible to introduce azathioprine, chloroquine, cyclosporine into the treatment regimen for autoimmune hepatitis. In case of ineffectiveness of immunosuppressive treatment of autoimmune hepatitis for 4 years, multiple relapses, side effects of therapy, the question of liver transplantation is also raised.
Prognosis and prevention
In the absence of treatment for autoimmune hepatitis, the disease steadily progresses; spontaneous remissions do not occur. The outcome of autoimmune hepatitis is liver cirrhosis and liver failure; 5-year survival rate does not exceed 50%. With the help of timely and well-conducted therapy, it is possible to achieve remission in most patients; at the same time, the survival rate for 20 years is more than 80%. Liver transplantation gives results comparable to drug-induced remission, a 5-year prognosis is favorable in 90% of patients.
With autoimmune hepatitis, only secondary prevention is possible, including regular monitoring by a gastroenterologist (hepatologist), monitoring the activity of liver enzymes, the content of gamma globulins, autoantibodies for timely strengthening or resumption of therapy. Patients are recommended a gentle regime with a restriction of emotional and physical exertion, diet, withdrawal from preventive vaccination, restriction of medication intake.