Autoimmune hepatitis

Autoimmune hepatitis ( Latin Autoimmune hepatitis ) is a chronic inflammatory liver disease characterized by the presence of typical autoantibodies, an increase in gamma globulins and a good response to immunosuppressive therapy. Despite advances in the study of the disease over the past 50 years, autoimmune hepatitis (AIH) is considered one of the most difficult problems in hepatology. The etiology of AIG is still unknown, and the course of the disease is chronic, undulating, with a high risk of liver cirrhosis.

History

Autoimmune hepatitis was first described in 1951 as chronic hepatitis in young women, accompanied by hypergammaglobulinemia, which improves with adrenocorticotropic therapy ^[3] . In 1956, a relationship was found between AIH and the presence of antinuclear antibodies (ANA) in the blood, and therefore the disease was called lupus hepatitis. Between 1960 and 1980 in a number of clinical studies, the effectiveness of AIG monotherapy with steroid drugs, as well as in combination with a cytostatic agent, azathioprine, has been proven. AIH was the first liver disease whose drug therapy has been proven to increase the life expectancy of patients.

Epidemiology

Autoimmune hepatitis is a relatively rare disease. The prevalence in Europe is 16-18 cases per 100,000 people. Among women with AIH, women predominate (80%) (according to the latest data (2015), the ratio of women to men is 3: 1). There are two peaks of incidence: at 20-30 years and at 50-70 years. However, according to recent data, there is a widespread increase in the incidence of AIG among all age groups in both men and women ^[4] , and is 15–25 cases per 100,000 people.

Etiology

There are 2 types of autoimmune hepatitis. Type 1 AIH is characterized by a positive titer of antinuclear antibodies (ANA) and / or smooth muscle antibodies (ASMA). Type 2 AIH is characterized by a positive titer of microsomal antibodies against the liver and kidneys (LKM-1) and / or anti-LC1. Although the etiology of AIH remains unknown, the most likely hypothesis is the influence of environmental factors on the immune system in genetically predisposed individuals.

Clinical picture

The debut of autoimmune hepatitis can occur at any age and among people of all nationalities. It usually proceeds with a clinic of chronic hepatitis, but in 25% of cases it can start as acute, including fulminant hepatitis. Therefore, the diagnosis of all cases of fulminate hepatitis with acute liver failure should include the exclusion of AIH. In most cases, nonspecific symptoms predominate, such as weakness, fatigue, and joint pain. Jaundice, a pronounced venous network on the anterior abdominal wall, and bleeding from the upper gastrointestinal tract indicate a progression of the disease with an outcome in cirrhosis. Often, other diseases occur in patients with AIH, especially immune-mediated ones, such as autoimmune thyroiditis, rheumatoid arthritis, Sjögren’s disease, vitiligo, glomerulonephritis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease) and others.

Diagnostics and differential diagnostics

Based on the determination of specific autoantibodies and the exclusion of other causes of hepatitis. Characteristic:

1. The prevalence of ALT over AST in the blood (de Ritis index <1);
2. Exclusion of viral hepatitis (hepatitis A, B, C, E);
3. The exclusion of toxic hepatitis (a thorough history: the exclusion of alcohol in terms of pure ethyl alcohol> 25 g / day; taking potentially hepatotoxic drugs);
4. The exception of hemochromatosis (determination of the level of ferritin and serum iron in the blood);
5. Exclusion of alpha-1-antitrypsin deficiency (determination of the concentration of alpha-1-antitrypsin in the blood);
6. Exclusion of Wilson's disease (normal levels of ceruloplasmin in the blood and copper content in daily urine);
7. Increased blood IgG> 1.5 times;
8. Detection of a positive titer of specific autoantibodies (ASMA; LKM-1; anti-LC1);

The “Gold Standard” is a liver biopsy with a clarification of the micromorphological diagnosis. The morphological picture corresponds to severe chronic hepatitis. The activity of the process is expressed unevenly, and some areas may be almost normal. Cell infiltrates are visualized, primarily from lymphocytes and plasma cells, which penetrate between the liver cells. Enhanced septum formation isolates groups of liver cells in the form of “rosettes”. Fatty degeneration is absent. Cirrhosis develops rapidly. Obviously, chronic hepatitis and cirrhosis develop almost simultaneously.

In order to diagnose autoimmune hepatitis, a special point scale has been developed for The Revised International Autoimmune Hepatitis Group Modified Scoring System ^[5]

Treatment

The goal of therapy is to prevent further progression of the disease, is to normalize the level of ALT / AST and IgG in blood tests.

• In all cases of diagnosis of AIH, prolonged immunosuppressive therapy is indicated;
• As immunosuppressive therapy, glucocorticosteroids are prescribed (monotherapy or in combination with cytostatics (azathioprine));
• Cancellation of therapy is possible no earlier than after 5 years of stable drug remission and subject to a control liver biopsy (exclusion of histological activity of hepatitis);
• In the case of repeated exacerbations of the disease and / or hormone-resistant course, alternative treatment regimens (cyclosporin A, mycophenolate mofetil; infliximab; rituximab) may be used;

Features of the course in childhood

The debut of autoimmune hepatitis in childhood is characterized by a more aggressive course and early development of liver cirrhosis. According to the literature, at the time of diagnosis, 43.7% of children with AIH type 1 and 70% of children with AIH type 2 already had a picture of formed liver cirrhosis.