Autoimmune Hepatitis

  • Prevalence
  • How does hepatic tissue change?
  • What disorders of the immune response cause hepatitis?
  • Symptoms of autoimmune hepatitis
  • By what analyzes are the probable pathologies judged?
  • Types of autoimmune hepatitis
  • Why do cross reactions occur?
  • How is the relationship with chronic hepatitis C assessed?
  • Diagnostics
  • Treatment of autoimmune hepatitis
  • What factors determine the prognosis of the disease?
  • Related Videos

Hepatitis (inflammation) of the liver of autoimmune etiology was first described in 1951 in a group of young women. Then, its main distinguishing feature was a high level of gamma globulins and a good reaction to the therapy with adrenocorticotropic hormone.

Modern views on autoimmune hepatitis significantly expanded, thanks to the disclosure of the secrets of immunology. However, the original cause of the disease, which leads to the production of antibodies in serum, remains unclear.

The disease is characterized by a chronic course with periods of exacerbations and a significant risk of transition to cirrhosis of the liver. Cure it is not yet possible, but the combination of cytostatics and steroid hormones can prolong the life of patients.


Autoimmune hepatitis refers to rare diseases. In European countries, there are 16-18 cases per 100,000 population. According to the data of 2015, in some countries it reaches 25. Women are sick 3 times more often than men (some authors believe that 8 times). Recently, the growth of the disease in both men and women has been documented.

Statistics revealed two "peak" detection rates:

  • among young people 20-30 years;
  • closer to old age in 50-70 years.

Studies show that in Europe and North America, autoimmune hepatitis accounts for one-fifth of all chronic hepatitis, and in Japan it rises to 85%. Perhaps this is due to a higher level of diagnosis.

Mechanism of autoimmune hepatitis
The simplified scheme of pathogenesis is considerably outdated and does not answer many questions

How does hepatic tissue change?

Histological analysis determines the presence in the liver of inflammation and necrosis areas around the veins (periportal). The picture of hepatitis is expressed by bridge necrosis of the liver parenchyma, a large accumulation of plasma cells in infiltrates. Lymphocytes can form follicles in portal ways, and surrounding liver cells turn into glandular structures.

Lymphocytic infiltration is located in the center of the lobes. Inflammation extends to the bile ducts and cholangiols of the portal tract, although septal and interlobular movements do not change. In hepatocytes, fat and hydropic dystrophy is found, cells are filled with fatty inclusions and vacuoles with fluid.

The disease is characterized by a rapid outcome in cirrhosis with hepatic insufficiency, portal hypertension.

What disorders of the immune response cause hepatitis?

Investigations of immunologists revealed that the final result of immune reconstructions is a sharp decrease in immunoregulation processes at the level of tissue lymphocytes. As a result, antinuclear antibodies to smooth muscle cells, lipoproteins appear in the blood. Often, violations are found, similar to systemic changes in red lupus erythematosus (LE phenomenon). Therefore, the disease is also called "lupoid hepatitis."

A lot of human antigens are involved in the reaction with antibodies. They are designated by immunologists alphabetic and digital abbreviations. Names can mean something only for specialists:

  • HLA,
  • MHC,
  • B14,
  • DQ2,
  • DR4,
  • DR3,
  • C4AQ0,
  • AIRE-1.

It is believed that the triggering cause of an autoimmune process may be additional factors-viruses:

  • hepatitis A, B, C;
  • Epstein-Barra;
  • herpes (HHV-6 and HSV-1).
This role is also played by the decay products of some medications

Symptoms of autoimmune hepatitis

In half of the cases, the initial symptoms of autoimmune disease appear at the age of 12 to 30 years. The second "peak" appears in women after the establishment of menopause menopause. 1/3 part is characterized by acute course and inability to distinguish from other acute forms of hepatitis in the first 3 months. In 2/3 cases the disease has a gradual development.

Patients note:

  • the growing heaviness in the hypochondrium on the right;
  • weakness and fatigue;
  • in 30% of young women menstruation stops;
  • possibly yellowing of the skin and sclera;
  • enlargement of the liver and spleen.

Characteristic combination of signs of liver damage with disorders of immunity, expressed in the following: skin rashes, itching, ulcerative colitis with pain and stool disorder, progressive thyroiditis (inflammation of the thyroid gland), stomach ulcer.

The patient may be hospitalized with severe pericardial effusion or myocarditis, temperature, shortness of breath, changes in the radiograph and ECG.

Pathognomonic symptoms of hepatitis of allergic nature are absent, therefore during diagnostics it is necessary to exclude:

  • viral hepatitis;
  • Wilson-Konovalov's disease;
  • other alcoholic and non-alcoholic liver damage (drug hepatitis, hemochromatosis, fatty dystrophy);
  • pathology of the hepatic tissue, in which an autoimmune mechanism takes place (biliary primary cirrhosis, sclerosing cholangitis).

The onset of autoimmune hepatitis in children is accompanied by the most aggressive clinical course and early cirrhosis. Already at the stage of diagnosis in half the cases children have developed cirrhosis of the liver.

Cirrhosis of the liver
One of the complications of the pathological process

By what analyzes are the probable pathologies judged?

In the analysis of the blood show:

  • Hypergammaglobulinemia with a decrease in the proportion of albumins;
  • the increase in transferase activity is 5-8 times;
  • positive serological test for LE cells;
  • tissue and antinuclear antibodies to tissues of the thyroid gland, stomach mucosa, kidneys, smooth muscles.

Types of autoimmune hepatitis

Depending on the serological responses, autoantibodies detected, three types of disease are distinguished. It turned out that they differ in the course, the prognosis of the response to therapeutic measures and the choice of the optimal treatment for autoimmune hepatitis.

Type I- was called "anti-ANA positive, anti-SMA." Antibody antibodies (ANA) or anti-smooth muscle antibodies (SMA) are found in 80% of patients, more than half of cases give a positive response to cytoplasmic antineutrophil autoantibodies of p-type (pANCA). Striking any age. Most often - 12-20 years and women in menopause.

For 45% of patients, the disease for 3 years without medical intervention will end with cirrhosis. Timely treatment provides a good response to corticosteroid therapy. In 20% of patients, long-term remission is maintained even with the abolition of immunosupplementation treatment.

Type II- differs presence of antibodies to cellular microsomes of hepatocytes and kidneys, is called "anti-LKM-1 positive". They are found in 15% of patients, more often in childhood. Can be combined in combination with a specific hepatic antigen. Adrift is more aggressive.

Alcoholic Toxic Hepatitis

Cirrhosis during the three-year observation develops 2 times more often than in the first type. More resistant to medicines. The abolition of drugs is accompanied by a new aggravation of the process.

Type III- "anti-SLA positive" to the hepatic soluble antigen and to the hepatic-pancreatic "anti-LP". Clinical signs are similar to viral hepatitis, hepatic biliary cirrhosis, sclerosing cholangitis. Gives cross-serological reactions.

Why do cross reactions occur?

The difference in types suggests that it should be used in the diagnosis of autoimmune hepatitis. This is seriously hampered by cross reactions. They are typical for different syndromes in which immune mechanisms are involved. The essence of the reactions is a change in the stable connection of certain antigens and autoantibodies, the emergence of new additional reactions to other stimuli.

Cross reactions
The origin of cross reactions remains unknown

Explained a special genetic predisposition and the emergence of an independent disease, while unexplored. For autoimmune hepatitis, cross reactions present serious difficulties in differential diagnosis with:

  • viral hepatitis;
  • hepatic biliary cirrhosis;
  • sclerosing cholangitis;
  • cryptogenic hepatitis.

In practice, cases of the transition of hepatitis to sclerosing cholangitis after several years are known. Cross-sectional syndrome with biliary hepatitis is more typical for adult patients, and with cholangitis for children.

How is the relationship with chronic hepatitis C assessed?

It is known that the course of chronic viral hepatitis C is marked by pronounced auto-allergic features. Because of this, some scientists insist on his identity with autoimmune hepatitis. In addition, pay attention to the relationship of viral hepatitis C with various extrahepatic immune signs (in 23% of patients). The mechanisms of this association are still inexplicable.

But it has been established that a certain role is played in it by the reaction of proliferation (increase in the number) of lymphocytes, the release of cytokines, the formation of autoantibodies and the deposition of antigen + antibody complexes in the organs. A definite dependence of the frequency of autoimmune reactions on the gene structure of the virus was not revealed.

Hepatitis virus
The most acceptable view is that the virus is an activator (trigger) of the formation of autoimmune processes

Due to its properties, hepatitis C is often accompanied by many different diseases. These include:

  • herpes dermatitis;
  • autoimmune thyroiditis;
  • red systemic lupus erythematosus;
  • ulcerative nonspecific colitis;
  • nodal erythema;
  • vitiligo;
  • hives;
  • glomerulonephritis;
  • fibrosing alveolitis;
  • gingivitis;
  • local myositis;
  • hemolytic anemia;
  • thrombocytopenic idiopathic purpura;
  • flat lichen;
  • pernicious anemia;
  • rheumatoid arthritis and others.
Rheumatoid arthritis
Typical changes in the hands of rheumatoid arthritis


The methodological recommendations adopted by the international group of experts establish criteria for the probability of diagnosing autoimmune hepatitis. Significance of the markers of antibodies in the serum of a patient is important:

  • antinuclear (ANA);
  • to microsomes of the kidneys and liver (anti-LKM);
  • to smooth muscle cells (SMA);
  • hepatic soluble (SLA);
  • hepatic-pancreatic (LP);
  • asialo-glycoprotein to receptors (hepatic lectin);
  • to the plasma membrane of hepatocytes (LM).

In this case, it is necessary to exclude the patient from the connection with the use of hepatotoxic drugs, blood transfusions, alcoholism. The list also includes a link with infectious hepatitis (by serum activity markers).

The level of immunoglobulin type G (IgG) and γ-globulins should exceed normal not less than 1.5 times, in the blood there is an increase in transaminases (aspartic and alanine) and alkaline phosphatase.

The recommendations take into account that from 38 to 95% of patients with biliary cirrhosis and cholangitis give identical reactions to markers. It is proposed to combine them with the diagnosis of "cross syndrome". In this case, the clinical picture of the disease is mixed (10% of cases).

For biliary cirrhosis, the indicators of cross-syndrome are two of the following:

  • IgG exceeds the norm by 2 times;
  • Alanine aminotransaminase is increased 5 or more times;
  • antibodies to smooth muscle tissue are detected in titer (dilution) more than 1:40;
  • in the biopsy of the liver are determined stepped periportal necrosis.

The application of the indirect immunofluorescence technique can technically give a false positive response to antibodies. The reaction on the glass (invitro) is not able to fully correspond to changes in the body. This has to be taken into account in the studies.

For the syndrome of adhesive cholangitis are characteristic:

  • signs of cholestasis (bile retention) with fibrosing of tubular walls;
  • often there is concomitant inflammation of the intestine;
  • cholangiography - the study of patency of the bile ducts is carried out by magnetic resonance imaging, transdermally and transversally, retrograde, ring-shaped narrowing structures within the bile ducts are revealed.
Histology of the liver with bile congestion
A liver biopsy shows at an early stage changes in the small intrahepatic ducts (edema and proliferation or complete disappearance), bile stagnation

Diagnostic criteria for cross-sectional syndrome with cholangitis are:

  • the growth of transaminases and alkaline phosphatase;
  • in half of patients the level of alkaline phosphatase is normal;
  • increase in the concentration of immunoglobulins of type G;
  • detection of serum antibodies SMA, ANA, pANCA;
  • typical confirmation by cholangiography, histological examination;
  • association with Crohn's disease or ulcerative colitis.

Treatment of autoimmune hepatitis

The aim of the therapy is to prevent the progression of the autoimmune process in the liver, the normalization of the indices of all metabolic species, the content of immunoglobulins. A patient of any age is offered to reduce the load on the liver with a diet and lifestyle. Physical work should be limited, the sick person should be allowed to rest frequently.

In the period of remission, therapeutic exercise, contrast shower is shown.

Strictly forbidden reception:

  • alcohol;
  • chocolate and sweets;
  • fatty varieties of meat and fish;
  • any products containing fats of animal origin;
  • smoked and sharp products;
  • beans;
  • sorrel;
  • spinach.


  • lean meat and fish;
  • porridge;
  • soups, dairy and vegetable;
  • salads dressed with vegetable oil;
  • yogurt, cottage cheese;
  • fruit.

The method of roasting is excluded, all dishes are cooked in boiled form or steamed. At an exacerbation it is recommended to organize six meals a day, in the period of remission there is enough routine.

Problems of drug therapy

The complex pathogenetic mechanism of the disease forces us to reckon with the possible influence of the drugs themselves. Therefore, international experts have developed clinical recommendations in which indications for treatment have been determined.

Doctor and patient
Scheme of therapy is selected individually

To start a course of therapy, the patient should have enough clinical symptoms and laboratory signs of pathology:

  • Alanine transaminase is higher than normal;
  • aspartic - 5 times higher than the normal value;
  • gamma globulins in serum are increased 2 times;
  • characteristic changes in biopsies of liver tissue.

Relative indications are: absence of symptoms or weak expression, gamma globulin level below double the norm, concentration of aspartic transaminase reaches 3-9 norms, histological picture of periportal hepatitis.

Targeted treatment is contraindicated in the following cases:

  • the disease does not have specific symptoms of defeat;
  • accompanied by decompensated cirrhosis of the liver with bleeding from the esophagus of varicose veins;
  • Aspartic transaminase is less than three norms;
  • histologically, inactive cirrhosis, reduced number of cells (cytopenia), portal type of hepatitis.

As a pathogenetic therapy, glucocorticosteroids are used (Methylprednisolone, Prednisolone). These drugs have an immunosuppressive (supporting) effect on T cells. Increased activity reduces autoimmune reactions against hepatocytes. Treatment with corticosteroids is accompanied by a negative effect on the endocrine glands, the development of diabetes;

  • syndrome of "Cushing's";
  • hypertension;
  • osteoporosis of bones;
  • menopause in women.
Budesonide is more sensitive to cell receptors, less associated with negative manifestations

One type of drug is prescribed (monotherapy) or a combination with cytostatics (Delagil, Azathioprine). Contraindications for the use of Azathioprim are individual intolerance, suspicion of malignant neoplasm, cytopenia, pregnancy.

The treatment is carried out for a long time, at first large dosages are applied, then they switch to supporting ones. Cancellation is recommended after 5 years, subject to confirmation of persistent remission, including biopsy results.

It is important to consider that positive changes in the histological examination appear 3-6 months after clinical and biochemical recovery. It is necessary to continue taking drugs all this time.

With a steady course of the disease, frequent exacerbations in the treatment regimen include:

  • Cyclosporin A,
  • Mycophenolate mofetil,
  • Infliximab,
  • Rituximab.

When identifying a connection with cholangitis, Ursosan is prescribed with Prednisolone. Sometimes experts believe that it is possible to use interferon preparations for the treatment of autoimmune hepatitis in the calculation of the antiviral effect:

  • Roferon A,
  • Pegasys,
  • Reaferon,
  • Alfaferon,
  • Intron A,
  • Pegintron.
The preparations contain amino acids that are closest in composition to human interferon

Side effects include depressive state, cytopenia, thyroiditis (in 20% of patients), the spread of infection to organs and systems. In the absence of efficacy of therapy for a four-year period and the presence of frequent relapses, the only method of therapy is liver transplantation.

What factors determine the prognosis of the disease?

The prognosis of the course of autoimmune hepatitis is determined primarily by the activity of the inflammatory process. For this, traditional biochemical blood tests are used: the activity of aspartate aminotransferase is 10 times higher than normal, a significant excess of the gamma globulin count is observed.

It was found that if the level of aspartic transaminase exceeds the normal level by 5 times and the immunoglobulins of type E are twice as high, 10% of patients can hope for a ten-year survival rate.

With lower criteria for inflammatory activity, the indicators are more favorable:

  • For 15 years, 80% of patients can live, during this period, half formed liver cirrhosis;
  • With the involvement of central veins in the inflammation and liver lobes, 45% of patients die within five years, 82% of them have cirrhosis.

The formation of cirrhosis in autoimmune hepatitis is considered an unfavorable prognostic factor. 20% of these patients die within two years of bleeding, 55% can live 5 years.

Rare cases, not complicated by ascites and encephalopathy, give good results on therapy with corticosteroids in 20% of patients. Despite numerous studies, the disease is considered incurable, although there are cases of self-healing. There is an active search for methods of delaying liver damage.

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