Chronic active hepatitis. Chronic active hepatitis, symptoms and treatment

Chronic active hepatitis is a long-term inflammatory disease of the liver with a high tendency to develop into cirrhosis. Histological feature is the detection of lymphocytic and plasma cell infiltration in the portal tracts, which extends to the periportal zone in the form of stepwise necrosis. Other phenomena are bridging, multilobular necrosis, collagen formation and fibrosis with active formation of septa.

Under the influence of treatment or spontaneously, the disease can stabilize, but recovery with outcome in fibrosis is possible.

Etiological factors may include hepatitis B viruses, less commonly C, delta virus, medications, alcohol, metabolic disorders in Wilson-Konovalov disease, e^-anti-

trypsin deficiency. Idiopathic chronic active hepatitis includes autoimmune and cryptogenic variants.

We consider separately two variants of chronic active hepatitis - chronic active viral hepatitis (chronic active hepatitis with predominantly hepatic manifestations) and chronic autoimmune hepatitis (chronic active hepatitis with severe extrahepatic manifestations).

Chronic active hepatitis due to drug, alcohol and metabolic disorders set out in the relevant sections.

Chronic active hepatitis (CAH) is chronic disease liver, caused by exposure to three types of hepatotropic viruses and causing chronic hepatitis type B, chronic hepatitis type L (delta) and chronic hepatitis type C.

In most cases, a morphological examination of the liver reveals granular and vacuolar degeneration of hepatocytes with the formation of acidophilic bodies, less often - chronic hydropic degeneration and small focal necrosis. Dystrophic changes cells are similar to acute viral hepatitis. Quite often there are various pathological changes nuclei and hepatocytes.

This form of hepatitis is characterized by regenerative processes. There are large hepatocytes with large nuclei and nucleoli, diffusely scattered throughout the parenchyma or forming islands - regenerates. The cytoplasm of the cells of these islets is highly basophilic (brightly pyroninophilic when stained according to Brachet). In some punctates, numerous binucleate liver cells and thickened hepatic beams are found. The pathogenetic significance of regeneration is twofold. On the one hand, it ensures the preservation of liver function in conditions of severe degeneration and necrosis of hepatocytes. On the other hand On the other hand, the regenerative nodes create pressure on the surrounding tissue and blood vessels, causing postsinusoidal hypertension.

Changes in the portal tracts and periportal zone are usually most pronounced. The portal tracts are noticeably thickened, sclerotic, with strands of fibroblasts and fibrocytes, as well as a moderate proliferation of small bile ducts. From some tracts, thin fibrous layers with small blood vessels and strands of fibroblasts. In all portal fields, extensive lymphomacrophage infiltrates with an admixture of leukocytes were found, while in most punctates the infiltration was pronounced and diffuse (20). A small number of plasma cells can also be found in the infiltrates.

The nuclei of most stellate reticuloendotheliocytes retain their elongated shape, their cytoplasm is hardly noticeable. However, in some observations, the cells lining the sinusoids resemble lymphoid elements and monocytes in the shape of their nuclei. In most patients, in some areas, stellate reticuloendotheliocytes form small clusters - proliferates.

Inflammatory infiltration usually extends beyond the portal fields, into the lobules. In most patients with CAH it is pronounced, and the integrity of the border plate is compromised.

Peripheral stepwise necrosis of the parenchyma is characterized by the closure of hepatocytes by lymphocytes, plasma cells and macrophages, penetrating from the portal tracts into the surrounding parenchyma. The infiltrate destroys the border plate, hence the name “stepped necrosis.” In some areas between the beams, thick fuchsinophilic collagen fibers and foci of sclerosis appear.

In areas of stepped necrosis, lymphocytes with signs of aggression can be found, penetrating into the liver cells.

It is believed that stepwise necrosis is a consequence of the cytopathic effect of T-lymphocytes and the lymphotoxic activity of T-killer cells, as well as antibody-dependent cytolysis carried out by K-lymphocytes. With an insignificant degree of activity, periportal stepwise necrosis is limited to segments of the periportal zone, only part of the portal tracts are affected. A moderate degree of activity is characterized by the same changes, but the damage covers almost all portal tracts, inflammatory infiltrates and stepwise necrosis penetrate to the middle of the lobule.

Along with the described typical picture, there are more severe histological subtypes of CAH with bridging and multilobular necrosis. The appearance of bridge-like necrosis is characteristic of the pronounced activity of the process.

In case of CAH with bridging necrosis (under acute hepatitis, subacute liver necrosis) areas of parenchymal necrosis, stromal collapse and an inflammatory reaction are detected. It should be emphasized that the necrotic hepatocytes themselves may not be visible, and the bridges between the portal tracts and the central veins are made up of extensive lymphoid cell infiltrates and collagen fibers that dissect the lobules [Loginov A. S., Aruin L. I., 1985].

CAH with multilobular necrosis is the most severe form (sharply expressed degree of activity) and is characterized by massive necrosis of the parenchyma, spreading beyond the border.

face of the lobules, total destruction of several adjacent lobules, sometimes with a strong inflammatory reaction or collapse. In biopsy specimens, as a rule, stepwise necrosis is also visible.

The structural restructuring of the liver tissue, observed in some patients, gives reason to talk about the transition of chronic hepatitis to cirrhosis of the liver. In 25% of the patients with chronic active viral hepatitis we observed, the lobular architecture was noticeably disturbed in punctates; some portal tracts were elongated and connected to each other by thin fibrous bridges. Thin connecting layers, often extending from the portal tracts, divide some of the lobules into small fragments.

In chronic viral hepatitis C, histological changes are less pronounced than in hepatitis B. They are characterized predominantly by hydropic degeneration and focal microvesicular fatty degeneration of hepatocytes. Distinctive feature is the presence of acidophilic necrosis of single hepatocytes in the central parts of the lobule. In active forms, extended inflammatory infiltration and fibrosis of the portal tracts with partial destruction of the border plate and “stepped” necrosis of the peri-portal hepatic parenchyma are noted. In repeated liver punctures of patients with chronic hepatitis C, changes can vary between the histological findings of chronic active and chronic persistent hepatitis (the so-called fluctuating type of chronic hepatitis C).

Morphological markers of the hepatitis B virus. The viral etiology of CAH can be established not only by electron microscopic or immunomorphological detection of Dane particles, HBsAg and HB c Ag, but also using publicly available methods. Viral liver damage can be suspected by the presence of frosted glassy hepatocytes when examining preparations stained with hematoxylin and eosin or using the Van Gieson method. These are large hepatocytes with pale eosin-stained cytoplasm. Opaque glassy hepatocytes occur not only in the presence of HBsAg, but also in drug-induced and alcohol-induced lesions. However, in the presence of HBsAg, frosted glassy hepatocytes are stained with orcein and aldehyde fuchsin. Liver cells containing HBsAg are stained in paraffin sections with aldehyde fuchsin and orcein (Shikat reaction). The specificity of orcein staining was confirmed by parallel studies of HB s Ag in liver tissue using immunofluorescence and electron microscopy.

Clinical picture. In a number of patients with CAH of viral etiology, a direct connection can be traced with acute viral hepatitis, but in most cases, the acute phase of hepatitis and the appearance of clinical symptoms of chronic hepatitis are separated by 3-5 years or more. The disease begins gradually and is manifested by repeated episodes of mild jaundice, liver enlargement and a number of nonspecific symptoms.

Asthenovegetative syndrome is extremely characteristic: weakness,

severe fatigue, sometimes so severe that patients are forced to spend 5 to 7 hours in bed during the daytime. There are often complaints of poor performance, nervousness, and a depressed state of mind (hypochondria). Characterized by a sharp weight loss (5-10 kg).

Pain in the liver area - quite common symptom diseases, they can be constant, aching, and sometimes very intense. Sharply intensifies after physical activity. The pain appears to be associated with pronounced inflammatory infiltration in the connective tissue (rich in nerves), in the portal and periportal zones, especially in the liver capsule. Some patients do not pain syndrome, but there is a feeling of heaviness and fullness in the right hypochondrium, independent of food intake; many patients complain of bad taste food products.

Dyspeptic syndrome rarely reaches significant severity; constant, painful nausea, aggravated by food and medications, accompanies exacerbation of the disease in most patients. Dyspeptic syndrome in patients with CAH can be associated with impaired detoxification function of the liver and concomitant damage to the pancreas.

"Small" syndrome liver failure, manifested by drowsiness, severe bleeding, jaundice and ascites, is observed in patients with severe necrotizing forms of CAH.

Cholestasis syndrome can be observed along with asthenovegetative disorders or dyspeptic syndrome. It is expressed by transient skin itching, increased levels of bilirubin, cholesterol, alkaline phosphatase activity, and GGTP in the blood serum.

During the period of exacerbation, there are such extrahepatic manifestations of the disease as pain in the joints and muscles with an increase in temperature to subfebrile levels, while there is no swelling or deformation of the joints. Patients report amenorrhea, decreased libido, and gynecomastia.

Extrahepatic signs (spider veins, hyperemia of the palms - “liver palms”) are often detected in this form of hepatitis. Their appearance coincides with biochemical and morphological signs of the activity of the process and is not, as is often believed, an indication of liver cirrhosis. If clinical improvement is accompanied by a noticeable decrease or disappearance of spider veins, then hyperemia of the palms remains for a long time, often until “biochemical remission”.

Hepatomegaly is detected in most patients with CAH. During the period of severe exacerbation, the liver protrudes 3-7 cm from under the costal arch, is moderately dense, the edge is pointed, palpation is painful. Remission is accompanied by a noticeable shrinkage of the liver: in many patients it protrudes by 2-3 cm or is palpated at the edge of the costal arch. Moderate enlargement of the spleen is common, but significant enlargement is rare. The onset of remission is accompanied by a decrease in the spleen. The activity of the reticuloendothelial tissue of the spleen in patients with CAH may be increased, therefore, in studies with "w Tc", the accumulation of colloid in the spleen is often increased, but to a lesser extent than in liver cirrhosis.

“Asymptomatic” CAH occurs latently in 25% of patients with complaints of intolerance to fatty and fried foods and alcohol. The examination reveals hepatomegaly, normal or slightly increased bilirubin levels, and an increase in aminotransferase activity by 3-5 times. Histological examination reveals a picture characteristic of CAH of moderate or insignificant activity. Liver cirrhosis develops latently, although it develops less frequently than in other cases.

Functional state of the liver. Exacerbation of CAH of viral etiology is characterized by hypergammaglobulinemia, hypoalbuminemia, increased thymol test levels and aminotransferase activity. Serum ALT activity is usually greater than AST activity. In most cases, the content of total protein and bilirubin in the blood serum increases. In remission of chronic active hepatitis, gamma globulin levels, functional tests and enzyme activity are rarely completely normalized; in most patients they only improve.

Serological indicators. The identification of hepatitis B markers in blood serum is of diagnostic importance.

Hepatitis B virus markers in the blood serum of patients with chronic active hepatitis of viral etiology: HBsAg is positive in most cases; anti-HBs negative; anti-HB c are positive, usually in high titers, some are positive anti-HB c IgM; HB c Ag positive or negative; DNA polymerase positive or negative; anti-HB e negative or positive.

The presence of HB e Ag and/or anti-HB c class IgM, as well as DNA polymerase in the blood serum indicates the replication of the hepatitis B virus; detection of anti-HB e may indicate a favorable prognosis of the disease.

Presence of HBsAg in various combinations with anti-HB class IgM and anti-HBe characterizes the phase of integration of the hepatitis B virus into the hepatocyte genome.

Features of the flow. CAH of viral etiology can have a continuously relapsing course or occur with alternating exacerbations and distinct clinical and sometimes biochemical remissions.

A continuously relapsing course of viral CAH can be observed for several years with very short clear intervals lasting up to a month.

In CAH with alternating exacerbations and remissions, exacerbations are usually frequent and long-lasting. Clinical remission occurs after 3-6 months, and improvement in biochemical parameters occurs after 6-12 mss. In some cases, functional tests are completely normalized during remission, although for a short period of time - usually up to 2-3 months. Some patients have several exacerbations within one year.

The prognosis of CAH depends on the stage of the disease at the time of diagnosis and histological signs of process activity, before

all types of necrosis. Ch. Hazzi (1986) determines a favorable prognosis for CAH primarily by the absence of signs of cirrhosis at the time of observation, with a 5-year survival rate observed in 80% of patients. In the presence of signs of cirrhosis, the 5-year survival rate is determined to be only 50%.

The possibility of a complete recovery is low. Stabilization of CAH is diagnosed by persistent clinical remission and improvement of biochemical parameters for at least 1-2 years, i.e., with weak or moderate activity of the process. It is important to emphasize the possibility of spontaneous remissions in 10-25% of patients.

According to the literature, 30-50% of all CAH develop into cirrhosis.

We spent dispensary observation for a period of 4 to 18 years in 66 patients with chronic active viral hepatitis. Stabilization of a process with weak or moderate activity was detected in 38 patients, cirrhosis of the liver developed in 28, of which 7 patients died.

The disease had a significant duration in many patients with CAH: from 5 to 10 years in 13 patients, from 10 to 15 years in 6 patients, and more than 15 years in 4 patients.

In some patients, when the process with weak activity stabilizes, the disease acquires the morphological features of chronic persistent hepatitis.

Long-term clinical observation shows that determining the variants of this form of hepatitis (chronic active hepatitis with exacerbations followed by clear remissions, or continuously relapsing) helps in choosing therapeutic tactics, but does not determine the outcome of the disease. The prognosis largely depends on how early treatment is started. Clinical examination of patients early stage significantly improves the prognosis.

The results of dispensary observation, indicating stabilization and ongoing activity of the process without signs of cirrhosis, refute the opinion about the fatal inevitability of the transition of this form of hepatitis to cirrhosis of the liver.

Chronic active viral hepatitis C, like its acute form, is much milder and has a more favorable prognosis than hepatitis B. Clinical symptoms are nonspecific, autoimmune manifestations are not observed. Apparently, the significant tolerance of the patient’s immune system to the pathogen determines the slow, erased course of the disease and minor biochemical changes in this form of chronic hepatitis. There is a tendency towards long-term remissions with complete normalization of biochemical test data, which leads to an erroneous conclusion about recovery. After a long-term remission, spontaneous increases in aminotransferase activity are observed, indicating the onset of an exacerbation. According to Ch. Hazzi (1986), the transition of hepatitis to cirrhosis is observed in 20-30% of patients, in most cases there is a tendency to transition to chronic persistent hepatitis.

This variant of CAH is accompanied by significant immune disorders. Clinical options A similar pathological process has been described under various names: active juvenile cirrhosis, lipoid hepatitis, subacute hepatitis, autoimmune hepatitis, plasma cell hepatitis, liver disease in young women with hypergammaglobulinemia, progressive hypergammaglobulinemic hepatitis. Each of these names dogmatizes one symptom of the disease. The term “autoimmune hepatitis”, emphasizing the uniqueness of the pathogenesis and clinical manifestations of the disease and the most common one, was chosen by us to designate this variant of CAH, which occurs with the most striking extrahepatic manifestations and often with a pronounced activity of the process.

Morphological characteristics. These are lymphomacrophagic elements, plasma cells, and in smaller numbers segmented nuclear leukocytes.

A distinctive feature of this form of hepatitis is the identification large quantity plasma cells at an early stage of the disease. In our observations, the transition to cirrhosis did not indicate an inactive stage of the disease. The formation of cirrhosis was detected in patients with undiminished activity of the process and a malignant course during the first and second years of the disease.

Clinical picture. The incidence of chronic autoimmune hepatitis is unknown, although most of the diseases have been described in Western Europe and the USA, and in our country - in the European part, but there are reports of cases of HBsAg-negative chronic active hepatitis with autoimmune manifestations in India. Among those sick with this form of hepatitis, the majority were girls and young women aged 10-30 years, less often women in menopause.

The ratio of women to men in autoimmune hepatitis is 3:1, while chronic viral hepatitis is more often observed in men. We observed 28 women with chronic autoimmune hepatitis aged 11-52 years and two men aged 14 and 42 years, while 10 patients were under 20 years old at the onset of the disease,

The onset of autoimmune hepatitis. In some patients initial symptoms indistinguishable from those in acute viral hepatitis. Periods of weakness, anorexia, and dark urine were preceded by intense jaundice with an increase in bilirubin content to 100-300 µmol/l (6-17%) and aminotransferase activity more than 200 units, which became the reason for hospitalization with a diagnosis of “acute viral hepatitis”. In only one patient, the bilirubin level did not exceed 20.5 µmol/l (1.2 mg%) and the onset of the disease was regarded as an anicteric form of acute viral hepatitis. However, in contrast to acute hepatitis

the disease progressed, and over the next 1-6 months, symptoms of CAH began to appear.

Another variant of the onset of autoimmune hepatitis is characterized by extrahepatic manifestations, fever. Moreover, the disease for 1-5 years is mistakenly regarded as SLE, rheumatism, rheumatoid polyarthritis, myocarditis, etc. Thus, in one of the patients we observed, 14-year-old S, the disease began with intense pain in the knee joints, heel bones, and after 2 months hemorrhagic rashes appeared on the legs. Only six months later, icteric sclera and enlarged liver and spleen were discovered. In another observation for 3 years, the patient had low-grade fever, tachycardia, an increase in ESR to 50 mm/h, which served as a reason for the erroneous diagnosis of thyrotoxicosis and specific therapy.

The clinical picture in the late stages of autoimmune hepatitis is varied: slowly progressive jaundice, fever, arthralgia, myalgia, abdominal pain, itching and hemorrhagic rashes, hepatomegaly. Individual manifestations of this symptom complex reach varying intensities.

Fever was often combined with arthralgia and was present in all the patients we observed, and in most of them the temperature reached febrile levels. In some patients, an increase in temperature from 37.5 to 39 °C, combined with an increase in ESR to 40-60 mm/h, dominated the clinical picture, and liver disease was not initially diagnosed. The galloping course of the disease with fever and pronounced dysproteinemia forced differential diagnosis with reticulosis and liver cancer.

Arthralgia is one of the most common and persistent extrahepatic manifestations of the disease in patients with chronic autoimmune hepatitis. Mostly large joints of the upper and lower extremities are involved, and in some cases, the joints of the spine. 3. G. Aprosina described polyarthritis in patients with chronic active hepatitis. The configuration of the joints changed mainly as a result of periarticular inflammation and tendon-muscular syndrome.

Recurrent purpura is the most common skin lesion. It is characterized by hemorrhagic exanthems in the form of sharply defined dots or spots that do not disappear with pressure. Purpura often leaves behind a brownish-brown pigmentation. In some cases, there are lupus erythema, erythema nodosum, psoriasis, and focal scleroderma. All patients had endocrine disorders: amenorrhea, acne and stretch marks on the skin, hirsutism.

Jaundice in patients with autoimmune hepatitis is intermittent, noticeably increasing during periods of exacerbation. Often visible spider veins, hyperemia of the palms, expressed to varying degrees. The liver in most patients is enlarged, painful on palpation, and its consistency is moderately dense. Transient splenoma

galium only in some patients, ascites is observed very rarely - during periods of pronounced activity of the process. Despite numerous clinical symptoms, patients often remain in good general health, unlike patients with all other forms of chronic hepatitis.

CAH represents systemic disease with damage to the skin, serous membranes and internal organs; pleurisy, myocarditis, pericarditis, ulcerative colitis, glomerulonephritis, iridocyclitis, Sjogren's syndrome are detected, lesions are described thyroid gland, secondary amenorrhea, Cushing's syndrome, diabetes, generalized lymphadenopathy, hemolytic anemia, various pulmonary and neurological diseases. However, these processes rarely predominate in the clinical picture; the most serious of them, including glomerulonephritis, often develop in the terminal stage of the disease,

Hepatic encephalopathy is observed in patients with lupoid hepatitis only in the terminal stage, but some patients, especially during periods of exacerbation, experience episodes of reversible “minor” liver failure.

Features of the flow. Most patients with autoimmune hepatitis experience a continuous course of the disease from the first symptoms to death. Exacerbations of the disease are manifested by jaundice, anorexia, abdominal pain, fever, hemorrhagic syndrome, hepatomegaly, sometimes splenomegaly and other symptoms.

During clinical observation of 25 patients for 3-18 years, we noted a continuously relapsing course in 12 patients; 6 of them died, respectively, 10, 12, 20 months, 2V 2, 5 and 8 years after the onset of clinical symptoms of liver failure. In 3 patients, hepatic coma developed after bleeding from dilated veins of the esophagus and stomach; 6 other patients are alive, and after 2-3 years, 5 patients developed cirrhosis of the liver. In 4 patients with macronodular cirrhosis, severe hepatocellular failure with encephalopathy and ascites was observed. Improvements in well-being are very short-term and depend on the dose of glucocorticoid drugs. Only one patient from this group had highly active chronic hepatitis.

In 13 patients with autoimmune hepatitis, clinical remission was obtained 2-4 years after its first manifestations. Stabilization of the process with weak or moderate activity was observed in 10 patients, transition to the inactive stage - in 3. In 9 of these patients, signs of transition to liver cirrhosis were found. In most patients, clinical remission is accompanied by improvement, but not normalization of biochemical parameters. Repeated exacerbations in patients with long-standing autoimmune hepatitis are milder with less severe symptoms and smaller deviations in biochemical parameters. Repeated exacerbations are stopped much faster than the first. In accordance with this, in

first acute period patients with diseases require long-term hospital treatment. In the patients we observed, the duration of the first hospitalization ranged from 4 to 14 months with short breaks. Repeated hospitalizations were significantly shorter and did not exceed 2 months.

Functional state of the liver. In all patients during periods of exacerbation of lupoid hepatitis, an increase in bilirubin content, aminotransferase activity, as well as disturbances in protein metabolism were detected. Less pronounced changes in these indicators were also observed in the majority of patients in remission. The serum bilirubin content in the observed patients did not exceed 188 µmol/l (11 mg%) and most often increased to 85.5 µmol/l (5 mg%). Hypergammaglobulinemia during periods of exacerbation reaches high numbers (35-48.7%). The diagnostic value of increased gamma globulin levels for chronic autoimmune hepatitis is widely discussed in the literature. The great significance of the indicator is evidenced by one of the names of this form of hepatitis - “progressive hypergamma-lobulinemic hepatitis”. It is fair to limit the value of this indicator due to the fact that other liver diseases may be accompanied by hypergammaglobulinemia. Hypoalbumicemia (below 40%) is observed during periods of pronounced activity of the process and does not indicate the formation of cirrhosis. The activity of aminotransferases increases significantly more than in all other forms of chronic hepatitis - in most patients it exceeds the norm by 7-10 times. In some patients, an increase in enzyme activity corresponds to the development of liver necrosis, but a clear parallelism between the severity of the disease and the activity of aminotransferases is not found. The increase in ALT is usually greater than that in AST, so the DeRitis coefficient is less than one. Note that exacerbations of the disease are characterized by a pronounced deviation in the thymol test and a sharp slowdown in the retention of bromsulfalein.

The most pronounced changes in biochemical parameters are observed at the onset of the disease and during the period of exacerbation. In some patients, during periods of remission, biochemical parameters deviate slightly from normal values.

Serological reactions and reactions that detect tissue antibodies are very often positive in CAH. These include the LE-cell phenomenon, antinuclear factor, and complement fixation reactions.

In the observed patients, LE cells and antinuclear factor were detected in 50% of cases at a serum dilution of 1:32. In some patients, antinuclear factor is detected with a negative reaction to LE cells. Chronic autoimmune hepatitis is characterized by a high frequency of detection of tissue antibodies in smooth muscles, gastric mucosa, thyroid gland, cells renal tubules, liver parenchyma. Own experience in studying smooth muscle antibodies (together with

E. L. Nasonov) allowed us to conclude that they are most often detected in CAH: their detection in high titers (1:160, 1:320 and above) is pathognomonic for the lupoid variant of CAH. It is important to emphasize their absence in SLE, chronic persistent hepatitis, and alcoholic liver damage. Determination of smooth muscle antibodies has essential for differential diagnosis of CAH with these diseases.

Forecast. Observations have shown that in chronic autoimmune hepatitis, the frequency of transition to cirrhosis is higher, and the prognosis is more serious than in patients with chronic viral hepatitis.

In more than a third of the observed patients, the formation of cirrhosis was latent against the background of stabilization of the process. Mortality is higher in patients with hepatitis-like onset, persistent cholestasis, ascites, episodes of hepatic coma, as well as necrosis in liver punctures. From our own observations and literature data it follows that the highest mortality occurs in the early, most active period of the disease. Patients who have survived the critical period have significantly best forecast. Among the patients we observed, 4 live more than 15 years after the onset of clinical symptoms.

Diagnostics various forms HAG. A feature of chronic autoimmune hepatitis is the predominantly plasma cell nature of the inflammatory infiltration in the portal tracts and intralobular stroma, and in chronic viral hepatitis it is lymphoid.

Functional liver tests and changes in enzyme activity are unidirectional, but when comparing the degree of deviations, a significant difference in their values ​​is determined.

Violation of protein synthetic, pigment, excretory-absorbent functions and increased activity of aminotransferases are much more pronounced in chronic autoimmune hepatitis. Significant differences are revealed when studying immunological parameters. According to our data, with CAH of viral etiology, the content of IgM and IgG was normal in 20%, and IgA in 40% of patients. In autoimmune hepatitis, an increase in the amount of immunoglobulins was detected in all patients. A comparative study of the content of immunoglobulins showed that the difference is statistically significant (Table 17). It should be emphasized that there is a significant increase in IgM content in autoimmune hepatitis.

High titers of antibodies to smooth muscle and specific hepatic lipoprotein are detected in all patients with chronic autoimmune hepatitis before treatment with glucocorticosteroid hormones. It is these indicators that can serve as reliable diagnostic criteria for autoimmune hepatitis with the morphological picture of CAH. The high frequency of detection of antibodies to smooth muscles in autoimmune hepatitis and their absence in SLE are essential in distinguishing between these diseases.

Difficulties usually arise in the initial stage of autoimmune hepatitis with pronounced systemic manifestations, as well as in the presence of kidney damage in a number of patients with CAH. Clinical data on glomerulitis in some patients with lupoid hepatitis from an immunological point of view have shown that serum containing antibodies to smooth muscles reacts with the cytoplasm of cells of the renal glomeruli, spleen, thymus, and lymph nodes. Moreover, the reaction of these antibodies with kidney glomeruli can cause their damage. This appears to lead to kidney damage in some patients with lupoid hepatitis.

The diagnosis of chronic active viral hepatitis is based on identifying markers of viral replication in blood serum and liver tissue and the results of a puncture biopsy, which gives an idea of ​​the form of hepatitis and histological criteria for the activity of the process. Antigenic markers of hepatitis B in blood serum are HB s Ag, HB c Ag, anti-HB e, anti-HB c, in liver tissue - HB c Ag.

The characteristic features of hepatitis B that distinguish it from hepatitis C are the possibility of developing hepatitis del-

ta-superinfections. It is delta infection that leads to the development of “unmotivated” exacerbations with pronounced cytolytic and cholestatic syndrome and significantly accelerates the progression of the disease with transition to liver cirrhosis.

Another feature that prevents hepatitis B is seroconversion, i.e. the disappearance of HB e Ag and the appearance of antibodies to it. Seroconversion develops spontaneously or after sudden withdrawal of large doses of glucocorticosteroids prescribed for a short period. Elimination of the pathogen by immunocompetent cells leads to lysis of affected hepatocytes and a severe exacerbation of the disease, sometimes with the development of hepatic coma. In most cases, after seroconversion, long-term remission occurs.

The diagnosis of hepatitis C is based on the detection of a marker (anti-HCV), as well as on a complex of anamnestic, clinical, biochemical and histological data. In this case, it is essential to exclude markers of hepatitis B and other etiological factors causing CAH.

Treatment. 1The regimen is the most important factor in maintaining compensation of liver function. It is necessary to timely eliminate hepatotoxic hazards: contact with hepatotropic poisons at work, lack of hygiene skills, alcohol consumption, unbalanced diet. Patients with CAH outside periods of exacerbation in the compensation stage should be recommended a lighter regimen. It is prohibited to work with physical and nervous overload. A short rest is indicated in the middle of the day. When the process worsens bed rest creates more favorable conditions for liver function as a result of increasing hepatic blood flow in the horizontal position of the patient and eliminating physical and mental stress. It is necessary to remove the drug burden, drugs that are slowly neutralized by the liver are not indicated - tranquilizers, sedatives, analgesics, strong laxatives for constipation, physiotherapeutic procedures for the liver area, balneotherapy are contraindicated. During the period of exacerbation of the disease, surgical operations and vaccinations can be performed only for health reasons.

Diet. In Russia, diet No. 5 according to the scheme of M.I. Pevzner has been adopted for patients with chronic hepatitis. It is energetically full, but with a limitation of extractive and cholesterol-rich substances (fatty meats and fish, spicy snacks, fried foods, salty, smoked foods). The amount of plant fiber is slightly increased. The daily diet contains 100-200 g of protein, 80 g of fat, 450-600 g of carbohydrates, which is 3000-3500 kcal.

When the process worsens, as well as when concomitant diseases gastrointestinal tract, diet No. 5a is prescribed, which is mechanically and chemically gentle. Vegetables and herbs are given in pureed form, meat - in the form of meatballs, quenelles, steam cutlets. Coarse vegetable fiber (rye bread, cabbage) and snacks are excluded.

tea. The amount of fat is limited to 70 g, including 15-20 g of vegetable fat. It is important to consider the amount of fat. For example, butter does not cause any unpleasant effects in patients with liver diseases. Pork, lamb and goose lard is prohibited.

Eating heavily can cause intense muscle contraction as a reflex. biliary tract and pain, so patients should eat at least 4-5 times a day.

It is advisable to use therapeutic factors aimed at normalizing hydrolysis and absorption, eliminating intestinal dysbiosis [Grigoriev P. Ya., Yakovenko E. P., 19901. Detoxification therapy includes intravenous drip administration of hemodeza (200-400 ml No. 3-8 ); orally - lactulose 30-60 ml 1-2 times a day.

Drug therapy for chronic active viral hepatitis.

In the treatment of chronic active hepatitis of viral etiology, the use of two groups of drugs is justified: immunostimulants and antivirals.

Immunostimulants. A group of drugs, including v-hodzt transfer factor, vaccineBCG, lrelarates of the thymus, zhvami- angry, prodigiosan, laser beams, sodium nucleinate, etc.

The premise for the use of immunostimulants was the assumption of F. Y. Dudley et al. (1972) about a defect in the immune system in response to the hepatitis B virus, as a result of which its elimination is impaired. Their use is based on two mechanisms drug effects- increased cellular immunoreactivity and decreased viral replication. A prerequisite for eliminating the virus is the destruction of hepatocytes containing the hepatitis B virus by cells of the lymphoid system. This explains the development of cytolysis syndrome during treatment with immunostimulants.

Most researchers note that the cytolysis syndrome observed at the beginning of taking levamisole is replaced by normalization of aminotransferase activity, improvement in the condition of patients, as well as a decrease in viral replication in a number of patients. This is manifested by the disappearance of HB e Ag from the blood serum, a decrease in the level of DNA polymerase activity, as well as a decrease in the number of hepatocytes containing HB s Ag and HB c Ag.

However, in some cases, despite a certain immunostimulating effect, the virus remains in the body.

Levamisole (deca) has greatest application in clinical practice. The drug is a nonspecific immunostimulant that improves the functional state of immune T cells and macrophages, reduces viral replication, and accelerates the lysis of some affected hepatocytes.

The study of the immune mechanisms of action of this anthelmintic drug began after a report from a French researcher.

calf G. Rcnoux (1971) about increasing the protective properties of a bacterial vaccine under its influence. Levamisole stimulates all subpopulations of T-lymphocytes, primarily T-suppressors, normalizes the interaction of T- and B-lymphocytes, and helps reduce the imbalance of T-helpers and T-suppressors. A.S. Loginov et al. (1983) noted a decrease in the biochemical and immunological activity of the process under the influence of decaa, but did not reveal a significant effect on the persistence of HB e Ag.

The use of levamisole in CAH can contribute to the development of severe forms of liver damage, including fulminant hepatitis; therefore, the prescription of immunostimulants requires strict indications. It should be considered that the presence of severe hepatocellular failure is a contraindication to the use of levamisole.

Taking into account literature data and our own experience, we formulated the following indications (criteria) for prescribing levamisole: clinical - absence of signs of severe disease; biochemical - bilirubin level is below 100 µm/l, ALT activity does not exceed the norm by 5 times; immunological - immunodeficiency in the system cellular immunity, impaired immunoregulation (deficiency of suppressor activity), the presence of markers of the hepatitis B virus replication phase in the blood serum or liver tissue.

Use various schemes treatment with levamisole: 1) 150-100 mg/day 3 days a week; 2) 150-100 mg/day every other day; a total of 7-10 doses are prescribed.

Maintenance doses are 100-50 mg per week. Course duration is from 1 month to 1 year or more.

To prevent severe cytolysis syndrome in some patients, Deca is used in combination with small doses of prednisolone.

Taking levamisole may be accompanied by the development of the following complications: 1) allergic; 2) neurological reactions; 3) changes in the gastrointestinal tract; 4) hematological - agranulocytosis (more often in women with HLA-B27), neutropenia, thrombocythemia.

Thymus preparations (thymalin, thymosin, T-activin) have the same indications as levamisole.

The use of thymus preparations in the treatment of chronic active liver diseases leads to an improvement in clinical and biochemical parameters in patients, which is apparently due to the immunoregulatory effect of these drugs: an increase in the number of T-lymphocytes, an improvement in the function of macrophages, a decrease in the cytopathic effect of lymphocytes, an increase in suppressive - weed activity of cells. It is possible that these drugs will occupy a significant place in the treatment of active liver diseases.

D-penicillamine. Marked positive effect during long-term treatment with D-psnicillamine of chronic active diseases

liver diseases, which was manifested in an improvement in general well-being, normalization of functional indicators, and removal of signs of activity of the pathological process during histological examination. It is important to emphasize that D-penicillamine is effective in cases of early fibrosis, the effect of the drug on mature connective tissue in case of cirrhosis it is ineffective.

In CAH of viral etiology, D-penicillamine has a collagen-inhibiting and immunoregulatory effect. The effect of the drug on the immunoregulatory system is to increase the number of T-suppressors and reduce the T-helper/T-suppressor ratio, inhibition of autoimmune reactions, which helps to reduce the activity of the pathological process.

Indications for use are the presence of young collagen in liver tissue, autoimmune reactions against the background of an imbalance of immunoregulatory cells. The dose of the drug is 600-900 mg/day. Duration of treatment is 1-6 months.

Antiviral drugs. In case of CAH of viral etiology, the study of the therapeutic effect of a number of antiviral drugs that suppress the replication of viral particles continues: interferon, adenine arabinoside and its derivative - arabinoside monophosphate, acyclovir, vidarabine.

Interferon is a drug with a wide range of effects, affecting not only the replication of the virus, but also the cells of the immune system. Along with the inhibitory effect of human leukocyte interferon on virus reproduction, its regulatory effect on T-lymphocytes and NK cells, which spontaneously lyse virus-infected cells, has been noted [G. R. Pare et al., 1980]. The effectiveness of therapy is determined by its timeliness; Early treatment helps to completely eliminate the virus. A number of studies have noted an unstable antiviral effect of interferon, so its combination with immunostimulating drugs is advisable.

Successful results have been obtained in the treatment of not only chronic active hepatitis B, but also C with injections of lymphoblast alpha interferon. Beta interferon is able to suppress the replication of not only viruses B and C, but also delta infection, although the effectiveness of the drug against HDV is clearly low . Adenine arabinoside and its soluble form for intramuscular injections adenine-arabinoside-5 monophosphate, like interferon, has an unstable antiviral effect. During treatment, there is a decrease in the level of hepatitis B virus DNA and DNA polymerase activity, less often a decrease in HBsAg, and seroconversion of HB e Ag, however, after discontinuation of the drugs, markers of viral replication reappear. Antiviral therapy is effective only in patients with a high level of viral reproduction. Treatment with adenine arabinoside and adenine arabinoside 5"-monophosphate may be complicated by the development of myalgia, polyneuropathy, dysfunction of the gastrointestinal tract, and thrombocytopenia.

Immunosuppressive drugs. Most controversial issue in the treatment of CAH of viral etiology is the use of glucocorticosteroid hormones. Proponents of prescribing prednisolone are based on the positive effect of immunosuppressants on immunopathological reactions involved in the pathogenesis of the disease. First, the production of factors by lymphocytes that inhibit the migration of leukocytes in response to liver-specific lipoprotein and HBsAg decreases. Taking prednisolone leads to a decrease in the activity of K-cells, which are important in the pathogenesis of the disease. There are reports of a decrease in hepatitis B virus replication under the influence of prednisolone. A decrease in the level of HB e Ag and DNA polymerase activity in the blood serum and the disappearance of HB c Ag from the liver tissue is accompanied by an improvement in histological parameters (Davis G. L. et al., 1981; Kumada H., 1982; Miyakawa H. et al., 1983]. The greatest effectiveness of immunosuppressive therapy was observed in patients with the presence of antibodies to HB e (anti-HBe positive),

A significant number of studies note the negative effect of therapy with immunosuppressive drugs in patients with CAH: increased replication of the hepatitis B virus, unfavorable course of the disease, and lack of improvement in morphological examination of liver punctures were revealed. Attention should also be paid to the fact that glucocorticoid hormones suppress the function of macrophages, which delays the elimination of the virus from the body.

Considering the well-founded danger of delayed persistence of the hepatitis B virus under the influence of prednisone therapy, we believe that the indications for prescribing immunosuppressants in these patients should be sharply limited.

The indication for prescribing prednisolone is only a severe clinical course of the disease with sharp changes in functional tests and enzyme activity, and the detection of bridge-like or multilobular necrosis of hepatocytes during histological examination.

N. S. Asfandiyarova (1988) noted the inducing effect on suppressor cells of medium doses of prednisolone in patients with chronic viral hepatitis with a high degree of activity. These data make it possible to explain the decrease in the activity of the pathological process by the suppression of immunopathological reactions.

The dose of prednisolone is 20-30 mg/day. The absence of a clear effect within 3-4 weeks from the use of medium doses of prednisolone serves as an indication for a gradual dose reduction and subsequent discontinuation of the drug. If the patient's condition improves, treatment can be continued from 6 months to 2 years.

With moderate and low activity of the pathological process, accompanied by significant immunodeficiency with an increase in suppressor function, the administration of prednisolone, delagil, azathioprine is not indicated, since this leads to a further deepening of the immunoregulation defect and, consequently, potentiation of virus activation and the activity of the pathological process. The use of prednisolone is also contraindicated for CAH caused by the C virus.

Patients with chronic viral hepatitis are advised to periodically prescribe drugs that increase the body's nonspecific immune resistance (vitamin therapy, sodium nucleinate, complevit, flakozid), which give a pronounced tonic effect.

Currently, the attitude towards the prescription of hepatoprotective drugs (Essentiale, Legalon, Karsil, Aika-phosphate, Katergen) for chronic viral hepatitis has been revised. These drugs do not reduce inflammatory activity; in addition, they can contribute to the intensification or appearance of intrahepatic cholestasis, therefore their use in CAH is not indicated.

Clinical examination of patients forms the basis of treatment of this form. Medical examinations are carried out regularly, at least once every six months, with the determination of the most informative indicators biochemical samples liver.

The appearance of increasing weakness and decreased performance, even in the absence of significant changes in biochemical blood tests, is an indication for hospitalization and the issuance of a certificate of incapacity for work. Patients with a highly active form of CAH of viral etiology are essentially group III disabled people. Employment is required, providing work that does not involve heavy physical exertion, frequent and long business trips, or driving. It is advisable to provide work with shortened working hours.

Treatment of chronic autoimmune hepatitis. Perennial clinical experience the use of glucocorticosteroids (GC) and new data on the pathogenesis of the disease allow us to consider them the drugs of choice for the treatment of chronic active autoimmune hepatitis.

One of the main drugs of glucocorticoid hormones - prednisolone - has wide range actions influencing all types of metabolism; it has a pronounced anti-inflammatory effect.

The decrease in the activity of the pathological process under the influence of prednisolone is due not only to its direct immunosuppressive effect on K cells. Of decisive importance, apparently, is the inducing effect of the drug on the suppressor activity of T-lymphocytes, which contributes to the inhibition of immune reactions. K. Nouri et al. (1982), adding prednisolone in vitro, noted restoration of T-suppressor function in patients with autoimmune CAH and the absence of this effect in viral lesions. The immunoregulatory effect of prednisolone is manifested when a high dose of the drug is prescribed.

I. R. Wands (1975), L. W. M. Lee et al. (1975) revealed a decrease in the frequency and intensity of immunopathological reactions directed against the liver tissue’s own antigens during treatment with prednisolone. A decrease in the frequency and degree of sen-

sibilization of lymphocytes to a specific hepatic lipoprotein, a decrease in the titer of antibodies to a specific hepatic lipoprotein and the level of IgG.

Azathioprine. Two mechanisms of the influence of aza-thioprine on the immune response have been registered: suppression of an actively proliferating clone of immunocompetent cells and elimination of specific inflammatory cells.

The effect of azathioprine on the primary and secondary immune response in experimental animals and humans has been noted. Azathioprine causes a decrease in the number of B-lymphocytes, the level of IgG and T-lymphocytes with helper activity.

The insufficient effect of treatment with azathioprine is associated with impaired activation of azathioprine or acceleration of its destruction in liver diseases. Prednisolone may promote activation of azathioprine; Azathioprine at a dose of 100 mg may be completely ineffective, but if it is prescribed along with prednisolone, even at a dose of 50 mg it gives a therapeutic effect. Currently, the combined administration of azathioprine with prednisolone is preferred for CAH.

The following indications (criteria) for immunosuppressive therapy prescriptions: clinical- heavy course of the disease with pronounced symptoms (jaundice, systemic manifestations, precoma, coma); biochemical - an increase in the content of gamma globules and novo above 30-40%, an increase in the activity of aminotransferases by more than 5 times, an increase in the thymol test by more than 3 times; immunological - increased IgG content above 2000 mg/100 ml, high titers of antibodies to SMA, impaired immunoregulation (increased helper activity, defective suppressor activity); morphological - the presence of stepped, bridge-like or multiform necrosis.

Use one of two schemes.

Scheme 1. High initial daily dose of prednisolone, 30-40 mg (rarely 50 mg) for autoimmune hepatitis. The duration of treatment is 4-10 weeks, followed by a reduction to a maintenance dose of 20-10 mg.

The dose of the drug is reduced slowly under the control of biochemical indicators of activity by 2.5 mg of prednisolone every 1-2 weeks to a maintenance dose, which the patient takes until complete clinical, laboratory and histological remission is achieved. If, when trying to reduce the dose, signs of disease relapse appear, the dose is increased again. Therapy with maintenance doses of GC should be long-term - from 6 months to 2 years, and in some patients with autoimmune hepatitis - up to 4 years or throughout life. When a maintenance dose of prednisolone is reached, according to A. S. Loginov, Yu. E. Blok (1987), alternating therapy is advisable, i.e., taking the drug every other day in a double dose, which prevents the development of adrenal insufficiency.

When prescribing other GCs, you can use the following equivalent: 5 mg prednisolone (1 tablet) = 4 mg triamsinolone (1 tablet) = 4 mg metyl prednisolone (1 tablet) = 0.75 mg dexamethasone (1.5 tablets).

When choosing a dose of GC, it is advisable to take into account the serum albumin content. A close relationship has long been noted between the incidence of side effects of GCs and serum protein levels. When the albumin content is less than 25 g/l side effects develop 2 times more often when prescribing the same dose of the drug. This is due to the fact that usually more 55% hormone in the blood is associated with albumin. With hypoalbuminemia, most of it remains free.

The side effects of GCs are well documented in the literature. As the dose of the drug increases and the duration of treatment increases, the development of ulcerations of the digestive tract, corticosteroid diabetes, osteoporosis, Cushing's syndrome, and decreased resistance to infections increases. At rapid decline daily dose of GC, especially at the end of long courses, the development of “withdrawal syndrome” is possible. It is believed that the “withdrawal syndrome” is associated with the development of insufficiency of the adrenal cortex and impaired autoimmune reactions. According to our observations, it is essential to prevent “withdrawal syndrome”, as well as other side effects GC has a combination with azathioprine or delagil, which allows the use of smaller doses of GC.

There are no absolute contraindications for the use of GCs in chronic autoimmune hepatitis. Relative contraindications are severe forms renal failure, focal infection, diabetes mellitus, peptic ulcer, decompensated hypertension, severe (2-3rd degree; see above) varicose veins of the stomach and esophagus, osteoporosis, spontaneous bacterial peritonitis.

Regimen 2: Prednisolone can be given in combination with azathioprine from the beginning of treatment or when the dose of prednisolone is reduced to prevent side effects of steroids. Prednisolone is prescribed at the beginning of the course at a dose of 15-25 mg/day, azathioprine - at a dose of 50-100 mg/day.

The maintenance dose of azathioprine is 50 mg, prednisolone is 10 mg. The duration of treatment is the same as when using prednisolone alone.

Both treatment regimens are equally effective, however, the incidence of complications with the combined use of prednisolone and azathioprine is 4 times less than with the use of prednisolone alone. With this combination, cosmetic defects develop in most patients by 2 years of treatment. More severe complications develop in 50%, and according to our data, in 20% of cases after 5 years from the start of therapy. It should be remembered that azathioprine has a depressant effect on bone marrow. The incidence of cytopenia is 11% when taking usual therapeutic doses. However, unlike cyclophosphamide and methotrexate, azathioprine never causes

generalized depression of bone marrow hematopoiesis. At the beginning of treatment, the number of leukocytes, especially neutrophils, often decreases. When the number of leukocytes decreases to 4-10 -3*10 /l, the dose is reduced, and at 3*10 -2*10 /l the drug is discontinued. In addition, during treatment with azathioprine, side effects may develop, such as skin rashes, gastrointestinal disorders, activation of focal infection, liver damage.

The hepatotoxic effect is manifested by transient nausea, loss of appetite, and a slight increase in bilirubin content. However, compared to other immunosuppressants, the hepatotoxic effect of azathioprine is much less pronounced. The combination of azathioprine with prednisolone, according to our observations, reduces the toxic effect of azathioprine.

It has been noted that long-term use of immunosuppressants may contribute to the occurrence of malignant neoplasms, mainly of the lymphoproliferative type. The oncogenic effect of immunosuppressants, in particular azathioprine, has been demonstrated in a number of experimental models. Thus, in mice treated with azathioprine, lymphomas were detected in 80% of cases, and in untreated mice - extremely rarely. Complications have not been described for liver diseases. However, the potential for tumor development is now increasing due to the duration of treatment and the increased use of immunosuppressive drugs.

Clinical improvement, according to our observations, develops in the majority of patients in the first weeks of treatment, biochemical remission - in 1/4 patients by the end of the 1st year. Histological remission with transition to inactive CAH or chronic persistent hepatitis develops later and is detected in 3 patients after 2 years.

Observations of recovered patients who had chronic autoimmune hepatitis showed that good results it is difficult to expect a biopsy if aminotransferase activity levels have not decreased or normalized. Half of the patients who responded to treatment relapsed within 6 months after stopping therapy. Liver cirrhosis is detected in cases where complete remission is not achieved during treatment, and sometimes even after successful treatment, accompanied by clinical and laboratory remission. Therapy with azathioprine in combination with prednisolone is most promising in the early stages of the disease.

Failures in the treatment of chronic autoimmune HBsAg-negative hepatitis develop in 20% of patients; 15-20% experience improvement without developing complete remission, and patients require maintenance therapy.

The lack of effect when using GC can be explained by insufficient doses of the drug. It is important to note that it was the researchers using 10-20 mg prednisolone that reported the adverse effect.

Dela Gil (chloroquine, hingamine, rezoquine, aralen) has a pronounced nonspecific anti-inflammatory effect.

It inhibits synthesis nucleic acids, activity of some enzymes, immunological processes. This served as the basis for the use of delagil for acute and chronic viral hepatitis.

Delagil is prescribed for mildly expressed activity of chronic autoimmune hepatitis. Daily dose delagil 0.25-0.5 g is combined with 10-15 mg of prednisolone. Subsequently, the dose of prednisolone is reduced to 5 mg, and then only delagil is prescribed.

The duration of treatment is from 1/2 to 6 months, and in some patients - up to 1/2-2 years.

Combination therapy with prednisolone and delagil, according to available observations, has a much better effect on biochemical parameters than treatment with prednisolone alone. When assessing the long-term results of treatment, it turned out that the process stabilizes much more often in patients receiving combination therapy.

Delagil allows you to use lower doses of prednisolone. Patients usually tolerate taking delagil orally in the indicated doses well. The following side effects with long-term use of delagil are described in the literature: dermatitis, dizziness, headache, nausea, sometimes vomiting, tinnitus, impaired accommodation, decreased visual acuity, leukopenia. Typically, these phenomena resolve on their own when the dose is reduced or the drug is discontinued. Combination therapy with prednisolone and delagil at a dose of 0.25-0.5 g did not cause deterioration in liver function.

Clinical examination. Patients with chronic autoimmune hepatitis are subject to dispensary observation, which includes monitoring correct mode with limitation of physical and emotional stress, employment taking into account the clinical form of the disease and the nature of production activity.

Most patients with chronic autoimmune hepatitis in the remission stage retain limited ability to work and can continue to work.

Drug therapy includes maintenance courses of immunosuppressive drugs not only for severe, but also for moderate and mild degrees of process activity. Courses of treatment with B vitamins and lipamide are prescribed 2-3 times a year. Follow-up examinations and laboratory examinations are carried out every 3-4 months, and when immunosuppressive therapy is continued - 1-2 times a month.

The appearance of signs of relapse (jaundice, systemic manifestations, increased aminotransferase activity, hyperbilirubinemia, hypergamma globules and non-mi I) indicates the need to resume therapy according to the above regimens in a hospital setting.

The problem of pregnancy and childbirth in patients with chronic autoimmune hepatitis cannot be solved unambiguously. There are reports that pregnancy and childbirth worsen the course of autoimmune chronic hepatitis, and immunosuppressive therapy does not significantly affect the fate of the fetus.

The point of view of A. S. Loginov and Yu. E. Blok (1987), who believe that pregnancy in patients with chronic autoimmune hepatitis can be allowed only after achieving stable remission and in the absence of clinically pronounced signs of portal hypertension, seems more justified and acceptable. Our experience shows that pregnancy poses a huge burden for the fetus and mother suffering from chronic autoimmune hepatitis.