Autoimmune Hepatitis - Diagnosis

Laboratory diagnostics of autoimmune hepatitis

1. Complete blood count: normocytic, normochromic anemia, mild leukopenia, thrombocytopenia, increased ESR. Due to severe autoimmune hemolysis, a high degree of anemia is possible.
2. General urine analysis: proteinuria and microhematuria may appear (with the development of glomerulonephritis); with the development of jaundice, bilirubin appears in the urine.
3. Blood chemistry: reveals signs of very active disease; hyperbilirubinemia with increased conjugated and unconjugated fractions of bilirubin; increased blood levels of specific liver enzymes (fructose-1-phosphate aldolase, arginase); decreased albumin content and significant increase in y-globulins; increased thymol and decreased sublimate tests. In addition to hyperbilirubinemia of the order of 2-10 mg% (35-170 mmol/l), a very high level of y-globulin in the serum is noted, which is more than 2 times higher than the upper limit of normal. Electrophoresis reveals polyclonal, occasionally monoclonal, gammopathy. Serum transaminase activity is very high and usually exceeds the norm by more than 10 times. Serum albumin level remains within normal limits until the late stages of liver failure. Transaminase activity and y-globulin level spontaneously decrease during the course of the disease.
4. Immunological blood test: decreased quantity and functional capacity of T-lymphocyte suppressors; appearance of circulating immune complexes and quite often lupus cells, antinuclear factor; increased immunoglobulin content. There may be a positive Coombs reaction, which reveals antibodies to erythrocytes. The most typical HLA types are B8, DR3, DR4.
5. Serological markers of autoimmune hepatitis.

It has now been established that autoimmune hepatitis is a heterogeneous disease in its serological manifestations.

Morphological examination of the liver in autoimmune hepatitis

Autoimmune hepatitis is characterized by pronounced infiltration of the portal and periportal zones by lymphocytes, plasma cells, macrophages, as well as step-like and bridge-like necrosis in the liver lobules.

Diagnostic criteria for autoimmune hepatitis

1. Chronic active hepatitis with pronounced lymphocytic and plasma cell infiltration of the portal and periportal zones, stepped and bridging necrosis of the liver lobules (morphological examination of biopsies).
2. Continuous progressive course of the disease with high hepatitis activity.
3. Absence of markers of hepatitis B, C, D viruses.
4. Detection in the blood of autoantibodies to smooth muscles and antinuclear antibodies in type 1 autoimmune hepatitis; antibodies to liver-renal microsomes in type 2 autoimmune hepatitis; antibodies to soluble liver antigen in type 3 autoimmune hepatitis, as well as lupus cells.
5. Severe systemic extrahepatic manifestations of the disease.
6. Efficiency of glucocorticosteroid therapy.
7. Mostly girls, young women, and women under 30 are affected, and less often, older women after menopause.

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Classification of autoimmune chronic hepatitis based on the spectrum of circulating autoantibodies

Some types of autoimmune hepatitis have no clearly identified cause, while others are associated with known agents such as thienic acid (a diuretic) or with diseases such as hepatitis C and D. In general, autoimmune hepatitis of unknown etiology has a more dramatic clinical picture, with higher serum transaminase activity and γ-globulin levels, liver histology suggesting higher activity than in cases of known etiology, and a better response to corticosteroid therapy.

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Autoimmune chronic hepatitis type I

Autoimmune chronic hepatitis type I (previously called lupoid) is associated with high titers of circulating antibodies to DNA and smooth muscle (actin).

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Autoimmune chronic hepatitis type II

Type II autoimmune chronic hepatitis is associated with LKM I autoantibodies. It is divided into subtypes IIa and IIb.

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Autoimmune chronic hepatitis type IIa

LKM I antibodies are found in high titers. This type is associated with severe chronic hepatitis. Other autoantibodies are usually absent. The disease predominantly affects girls and may be associated with type 1 diabetes, vitiligo, and thyroiditis. In children, the disease may be fulminant. A good response has been achieved with corticosteroid treatment.

The main antigen is a cytochrome belonging to the P450-2D6 subgroup.

In autoimmune chronic hepatitis type IIa, antibodies to soluble liver antigen can be found, but this does not provide grounds for identifying a special group of patients with autoimmune hepatitis.

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Autoimmune chronic hepatitis type IIb

LKM I antibodies are also found in some patients with chronic HCV infection. This may be due to common antigens (molecular mimicry). However, a more detailed analysis of microsomal proteins showed that LKM I autoantibodies in hepatitis C patients were directed against antigenic regions of P450-11D6 proteins that differ from those in autoimmune hepatitis in LKM-positive patients.

Thienylic acid. Another variant of LKM (II), detected by immunofluorescence, is found in patients with hepatitis caused by the diuretic thienylic acid, which is currently banned for clinical use, and which resolves spontaneously.

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Chronic hepatitis D

Some patients with chronic HDV infection have circulating LKM HI autoantibodies. The microsomal target is uridine diphosphate glutamyl transferase, which plays an important role in the elimination of toxic substances. The role of these autoantibodies in disease progression is unclear.

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Primary biliary cirrhosis and immune cholangiopathy

These cholestatic syndromes have their own markers, which in the case of primary biliary cirrhosis are represented by serum mitochondrial antibodies, and in the case of immune cholangiopathy - antibodies to DNA and actin.

Chronic autoimmune hepatitis (type I)

In 1950, Waldenström described chronic hepatitis occurring predominantly in young people, especially women. Since then, the syndrome has been given various names, which, however, have proven unsuccessful. In order not to rely on any one of the factors (etiology, gender, age, morphological changes), which are also not characterized by constancy, preference was given to the term "chronic autoimmune hepatitis". The frequency of use of this term is decreasing, which may be due to more effective detection of other causes of chronic hepatitis, such as medication, hepatitis B or C.

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Differential diagnosis of autoimmune hepatitis

A liver biopsy may be required to determine if cirrhosis is present.

Differentiation from chronic hepatitis B is carried out by determining hepatitis B markers.

Untreated patients with chronic hepatitis and antibodies to HCV may have circulating tissue autoantibodies. Some first-generation tests give false-positive results due to high serum globulin levels, but sometimes even second-generation tests show a positive result. Patients with chronic HCV infection may have circulating LKM II antibodies.

Distinction from Wilson's disease is vital. A family history of liver disease is essential. Hemolysis and ascites are common at the onset of Wilson's disease. Slit-lamp examination of the cornea for the Kayser-Fleischer ring is desirable. This should be done in all patients under 30 years of age with chronic hepatitis. Decreased serum copper and ceruloplasmin and elevated urinary copper support the diagnosis. Liver copper is elevated.

It is necessary to exclude the medicinal nature of the disease (taking nitrofurantoin, methyldopa or isoniazid).

Chronic hepatitis may be combined with nonspecific ulcerative colitis. This combination should be differentiated from sclerosing cholangitis, which usually has elevated alkaline phosphatase activity and no serum antibodies to smooth muscles. Endoscopic retrograde cholangiopancreatography is of diagnostic value.

Alcoholic liver disease. The anamnesis, presence of stigmata of chronic alcoholism and large painful liver are important for diagnosis. Histological examination reveals fatty liver (rarely associated with chronic hepatitis), alcoholic hyaline (Mallory bodies), focal infiltration of polymorphonuclear leukocytes and maximum damage to zone 3.

Hemochromatosis should be excluded by measuring serum iron.

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