Autoimmune hepatitis: diagnosis

Laboratory diagnosis of autoimmune hepatitis

1. General blood test: normocytic, normochromic anemia, indistinctly expressed leukopenia, thrombocytopenia, increased ESR. Due to expressed autoimmune hemolysis, a high degree of anemia is possible.
2. The general analysis of urine: there may be the appearance of proteinuria, microhematuria (with the development of glomerulonephritis); when jaundice develops, bilirubin appears in the urine.
3. Biochemical blood test: reveals signs of a very active disease; Hyperbilirubinemia with increased conjugated and non-conjugated bilirubin fractions; increase in blood levels of specific liver enzymes (fructose-1-phosphataldolase, arginase); decrease in albumin content and a significant increase in y-globulin; increase of thymol and reduction of trial samples. In addition to hyperbilirubinemia of the order of 2-10 mg% (35-170 mmol / l), there is a very high serum γ-globulin level, which is more than 2 times the upper limit of the norm. Electrophoresis reveals polyclonal, occasionally monoclonal, gammopathy. The activity of serum transaminases is very high and usually exceeds the norm by more than 10 times. The level of albumin in the serum remains within the limits of the norm until the late stages of liver failure. During the course of the disease, the activity of transaminases and the level of y-globulin decrease spontaneously.
4. Immunological analysis of blood: decrease in the number and functional capacity of T-lymphocytes-suppressors; the appearance of circulating immune complexes and quite often - lupus cells, antinuclear factor; increase in the content of immunoglobulins. There may be a positive Coombs reaction, it reveals antibodies to red blood cells. The most characteristic are HLA types of 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

For autoimmune hepatitis is characterized by severe infiltration of portal and periportal areas with lymphocytes, plasma cells, macrophages, as well as step and bridge necrosis in the liver lobules.

Diagnostic criteria for autoimmune hepatitis

1. Chronic active hepatitis with marked lymphocytic and plasma cell infiltration of portal and periportal zones, stepped and bridge-like necrosis of hepatic lobules (morphological study of biopsy specimens).
2. Continuous progressive course of the disease with a high activity of hepatitis.
3. Absence of markers of hepatitis B, C, D.
4. Detection in the blood of autoantibodies to smooth muscles and antinuclear antibodies at type 1 autoimmune hepatitis; antibodies to hepatic-renal microsomes in autoimmune hepatitis type 2; antibodies to soluble hepatic antigen in autoimmune hepatitis type 3, as well as lupus cells.
5. Expressed system extrahepatic manifestations of the disease.
6. Efficacy of glucocorticosteroid therapy.
7. Mostly girls, girls, young women under 30, mostly women of the older age group after menopause are ill.

[1], [2], [3], [4]

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

Some types of autoimmune hepatitis do not have a clearly established cause, others are associated with known agents such as thienyl acid (diuretic) or with diseases such as hepatitis C and D. In general, in autoimmune hepatitis of unknown etiology, there is a more vivid clinical picture for him a higher activity of serum transaminases and a level of y-globulin is characteristic; histological changes in liver tissue indicate a higher activity than in cases with known etiology, and the response to corticosteroid therapy is better.

[5], [6], [7], [8], [9], [10], [11]

Autoimmune chronic hepatitis type I

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

[12], [13], [14], [15]

Autoimmune chronic hepatitis type II

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

[16], [17], [18]

Autoimmune chronic hepatitis type IIa

Antibodies LKM I are found in high titres. This type is associated with a severe form of chronic hepatitis. Other autoantibodies are usually absent. The disease is more affected by girls and can be combined with type 1 diabetes, vitiligo and thyroiditis. In children, the disease can be fulminant. In the treatment of corticosteroids received a good answer.

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

In autoimmune chronic hepatitis type IIa, antibodies to soluble hepatic antigen can be found, but this does not provide a basis for isolating a particular group of patients with autoimmune hepatitis.

[19], [20], [21], [22], [23]

Autoimmune chronic hepatitis type IIb

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

Thienyl acid. Another variant of LKM (II), detected by immunofluorescence, is found in patients with hepatitis caused by currently prohibited for clinical use diuretic thienyl acid, which is independently resolved.

[24], [25], [26]

Chronic hepatitis D

Some patients with a chronic infection due to HDV have circulating autoantibodies LKM HI. The microsomal target is uridine diphosphate glutamyltransferase, which plays an important role in the elimination of toxic substances. The effect of these autoantibodies on the progression of the disease is not specified.

[27], [28], [29], [30],

Primary biliary cirrhosis and immune cholangiopathy

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

Chronic autoimmune hepatitis (type I)

In 1950, Waldenström described chronic hepatitis, which occurs mainly in young people, especially in women. From this moment the syndrome was given different names, which, however, proved unsuccessful. In order not to be based on any one of the factors (etiology, sex, age, morphological changes), which, moreover, do not differ in constancy, the preference was given to the term "chronic autoimmune hepatitis". The frequency of use of this term decreases, which may be due to more effective detection of other causes of chronic hepatitis, for example, taking medications, hepatitis B or C.

[31], [32], [33]

Differential diagnosis of autoimmune hepatitis

To clarify the issue of the presence of cirrhosis may require a puncture liver biopsy.

Differentiation with chronic hepatitis B is mediated by the identification of hepatitis B markers.

In untreated patients with chronic hepatitis and antibodies to HCV, circulating tissue autoantibodies can be detected. Some tests of the first generation give false positive results due to the high level of serum globulins, but sometimes even second-generation tests show a positive result. Patients with chronic HCV infection may have circulating LKM II antibodies.

Distinction with Wilson's disease is vitally important. The family history of the liver disease is of great importance. In the onset of Wilson's disease, haemolysis and ascites are often observed. It is desirable to examine the cornea with a slit lamp in order to detect the Kaiser-Fleischer ring. This should be done in all patients under the age of 30 with chronic hepatitis. The reduced content of copper and ceruloplasmin in the serum and an increased concentration of copper in the urine confirm the diagnosis. The content of copper in the liver is increased.

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

Chronic hepatitis can be combined with nonspecific ulcerative colitis. This combination should be differentiated with sclerosing cholangitis, which usually increases the activity of alkaline phosphatase and lack of serum antibodies to smooth muscles. Endoscopic retrograde cholangiopancreatography is of diagnostic importance.

Alcoholic liver disease. For the diagnosis, it is important to have an anamnesis, a stigma of chronic alcoholism and a large painful liver. Histological examination reveals fatty liver (rarely combined with chronic hepatitis), alcoholic hyaline (Mallory's body), focal infiltration by polymorphonuclear leukocytes and maximal lesion of zone 3.

Hemochromatosis should be excluded by determining serum iron.

[34], [35], [36], [37], [38], [39], [40]