Passive and active hepatitis C. Requirements for generics. Chronic reactive hepatitis

An exacerbation is characterized by the appearance of a pronounced asthenovegetative syndrome, manifested in fatigue, sometimes so severe that patients are forced to spend 5 to 7 hours in bed daytime. Often there are complaints of decreased performance, nervousness, depressed mood, and hypochondria. This symptom is a consequence of disorders of all types of metabolism that accompany this disease. Characteristic fast weight loss by 5-10 kg.

I am worried about pain in the right hypochondrium, almost constant, aching in nature, very intense, intensifying after physical activity. The pain syndrome is caused by inflammatory infiltration of the organ parenchyma and stretching of the liver capsule. Some patients experience equivalents of pain, manifested in a feeling of heaviness or; overflow in the area of the right hypochondrium and not dependent on food intake.

Dyspeptic syndrome is manifested by painful nausea, aggravated by food intake, and anorexia; with active hepatitis, it is most often associated with impaired detoxification function of the liver.

In some patients, a flu-like debut of the disease is possible, manifested by low-grade fever or high fever and hemorrhagic syndrome(bleeding from the nose, gums, subcutaneous hemorrhages, petechiae), which is caused by a decrease in prothrombin synthesis or thrombocytopenia.

Sometimes the initial symptom is a prolonged moderate increase in ESR and pain in the right hypochondrium.

In some patients without hepatomegaly, it is possible that the disease begins with extrahepatic manifestations - arthralgia, anemia, bleeding, persistent diarrhea.

Hepatomegadia occurs in the vast majority of patients with chronic active hepatitis. During the period of severe exacerbation, the liver protrudes from under the edge of the costal arch by 5 - 7 cm, it is moderately dense, the edge is pointed, and palpation is painful. During the period of remission, a slight enlargement of the liver may also persist (up to 2-3 cm) or it may be palpated at the edge of the costal arch. Hepatomegaly is often accompanied by splenomegaly, especially during the period of exacerbation of the process.

In severe cases of active hepatitis, there are manifestations of so-called “minor” liver failure, expressed in sleepiness, severe bleeding, the appearance of jaundice and ascites.

With this form of hepatitis, cholestasis syndrome is observed, which is characterized by transient skin itching, increased bilirubin, cholesterol, activity alkaline phosphatase.

During the period of exacerbation, extrahepatic manifestations are also possible: such as joint pain, myalgia, low-grade fever, amenorrhea.

Approximately 30% of patients have minor liver signs. Erythema of the palms (palmar erythema) is a symmetrical "spotty redness of the palms and soles, especially pronounced in the tenor and hypotenor areas, sometimes the flexor surfaces of the fingers. The spots turn pale when pressure is applied, and then quickly recover after the pressure stops. It is assumed that the hepatic palms are caused by arternovenous anastomoses. It should be remembered that this symptom can be observed during pregnancy, thyrotoxicosis, and septic endocarditis.

Telangiectasia ( spider veins, stellate angiomas) - consist of a pulsating central part and radial branching of vessels. The central artery of the stellate angioma under the epidermis is dilated, protrudes above the skin and resembles a star in shape. Telangiectasias are located on the neck, face, shoulders, hands, back, and on the mucous membrane of the upper palate. Their. sizes range from 1 mm to 1-2 cm. Improvement in the functional state of the liver is accompanied by a decrease in the number of angiomas and their disappearance. The mechanism of occurrence of this phenomenon is associated with an increase in the content of estrogen in the blood plasma.

Laboratory data.

General clinical blood tests do not reveal any specific changes: in 20-30% of patients it occurs moderately increased ESR, usually no more than 20-25 mm per hour, often, especially in women, moderate |aemia, the number of leukocytes_ usually slightly exceeds the lower limit of normal. Thrombocytopenia sometimes occurs. Severe thrombocytopenia or leukopenia is often caused by autoimmune genesis (formation of corresponding autoantibodies in the spleen).

Timely performance of basic biochemical liver tests is crucial for the early diagnosis of chronic active hepatitis. With an exacerbation of the process, the activity of aminotransferases, especially ALT, is increased by at least 3 times, which is an indicator of the activity of the inflammatory-necrotic process in the liver. It should be remembered that normalization of aminotransferase activity with increasing dysproteinemia may reflect the transition of active hepatitis to liver cirrhosis.

In chronic active hepatitis, the activity of gamma-hautamyltransferase increases. which helps in differential diagnosis with chronic persistent hepatitis. In the cholestatic version of active hepatitis, the activity of alkaline phosphatase increases. In severe, necrotic changes in the liver, the activity of cholinesterase synthesized by the liver and the prothrombin index decrease.

In 20-40% of patients with active chronic hepatitis, there is a slight increase in the content of bilirubin in the blood due to the direct fraction. Severe direct hyperbilirubinemia in combination with high activity of blood alkaline phosphatase is characteristic of the cholestatic form of chronic hepatitis. The increased concentration is not direct bilirubin may be due to concomitant Gilbert's syndrome or a hemolytic component, which is characteristic of viral infections.

Characterized by moderate dysproteinemia (serum gamma globulin within 18-20 g/l), accompanied by an increase in the thymol test. Serum total protein concentration in chronic active hepatitis viral etiology increased slightly in contrast to autoimmune hepatitis, which is characterized by severe hypergammaglobulinemia.

Chronic active hepatitis of viral etiology occurs long time latent. Serious complications associated with the development of liver cirrhosis arise 10-20 years after the onset of the disease. The course is characterized by a tendency towards spontaneous, often temporary remissions with complete or almost complete normalization of biochemical liver tests.

The possibility of recovery is negligible, and complete reversal is almost never observed.

There is an opinion that there are no sharp boundaries between chronic persistent hepatitis and chronic active hepatitis; transitional forms are possible. Both morphological forms can represent different stages of the evolution of chronic hepatitis in the same patient and mutually transform into each other. In some cases, persistent hepatitis reflects the phase of long-term remission of active chronic hepatitis.

Chronic active autoimmune hepatitis (idiopathic chronic autoimmune hepatitis, subacute hepatitis, lupoid hepatitis) is a separate form of chronic active hepatitis with extra-nocturnal manifestations and good sensitivity to corticosteroid therapy.

This disease was first described in 1950 by Waldenstrom; it occurs predominantly in women (80%), of which 50% become ill between the ages of 10 and 30 years.

Autoimmune active chronic hepatitis meets the 6 main criteria of an autoimmune process: inability to isolate the etiological factor; accelerated ESR; hypergammaglobulinemia; lymphohistocytic infiltration; the appearance of autoantibodies in the blood serum; positive therapeutic effect of glucocorticosteroids and immunosuppressive drugs.

In contrast to active chronic hepatitis of viral etiology, chronic autoimmune hepatitis is characterized by extremely rare clinical remissions, a rapid progressive course with the development of cirrhosis and liver failure, and a frequent combination of liver damage with autoimmune damage to other organs and systems. In some patients, the disease begins imperceptibly with symptoms of astnization, pain in the right hypochondrium, minor but persistent jaundice and patocellular type. Much more often, the disease debuts with a suddenly developed symptom complex of acute liver damage and is manifested by weakness, anorexia, dark urine, jaundice and pronounced hypertransferasemia, which is very reminiscent of acute viral hepatitis. However, a thorough examination reveals signs of chronic liver damage: cutaneous telangiectasia, palmar erythema, hepatosplenomegaly, hemorrhagic diathesis, leukopenia, a sharp increase in ESR, anemia. Women with such clinical manifestations often have amenorrhea and symptoms of hypercortisolism (moon face, acne, striae distensae in the abdomen, thighs and buttocks).

The disease can also begin with extrahepatic manifestations: high fever, resistant to antibiotic treatment, acute glomerulonephritis, autoimmune hepatic jaundice, lymphadenopathy, ulcerations of the skin of the legs, polyserositis and thrombocytopenic purpura.

Clinical picture on late stages autoimmune hepatitis is diverse. Jaundice is very characteristic, constant and progressive during the period of exacerbation. Spider veins and palmar erythema are often present. The liver is enlarged, painful on palpation, usually of a dense consistency. Some patients have an enlarged spleen.

One of the most characteristic extrahepatic manifestations of autoimmune hepatitis is arthralgia. The process involves mainly large joints of the upper and lower limbs, less often the joints of the spine.

Fever is often combined with arthralgia, the temperature reaches fibrillar levels and, as a rule, is not accompanied by chills.

During the period of exacerbation, skin manifestations appear, expressed in the development of recurrent purpura, which is characterized by hemorrhagic exanthemas in the form of sharply defined dots or spots that do not disappear with pressure; purpura often leaves behind a brownish-brown pigmentation.

Chronic active autoimmune hepatitis can be considered as a systemic disease with skin lesions (capillaritis, erythema nodosum, urticaria), Raynaud's syndrome, serous membranes, pleura, myocardium, pericardium, intestines (chronic diarrhea), kidneys (chronic pyelonephritis), nervous system, thyroid gland. However, the above-mentioned manifestations rarely prevail in the clinical picture and develop mainly in the terminal stage of the disease.

Laboratory data.

Autoimmune chronic active hepatitis is characterized by a combination of signs of anomaly immune system and severe damage to the liver parenchyma. In particular, ESR is increased, as a rule, more than 20 mm/hour, autoimmune anemia is increasing, hyperproteinemia is characteristic (at least 90-100 t/l, hypergammarotyainemia due to an increase in IgG (more than 18 g/l)), increased activity of aminotransferases in 5-10 times. Moderate hyperbilirubinemia with a predominance of the conjugated fraction, moderate, is often observed. a slight (no more than 2-fold) increase in alkaline phosphatase activity, prolongation of prothrombin time and decrease in plasma albumin levels. In 5-7% of patients, wolf cells are found in the blood. This form of chronic hedatitis is characterized by the appearance in the blood plasma of high titers of tissue antibodies to smooth muscles, the mucous membrane of the stomach, the thyroid gland, and the cells of the renal tubules. The appearance of these antibodies plays an important role in differential diagnosis with systemic lupus erythematosus (given systemic manifestations, changes from the blood side), for which they are not typical. These antibodies are also not found in chronic persistent hepatitis and alcoholic lesions liver.

The prognosis is unfavorable, life expectancy, if cortical steroids are not prescribed, does not exceed 5 years.

Chronic active hepatitis of alcoholic etiology

Men are affected 2.5 times more often than women. The clinical picture of this form of hepatitis consists of pronounced metabolic and systemic stigmata of alcoholism and moderate symptoms of hepatitis itself.

Low nutrition is often observed due to anorexia, insufficient intestinal absorption and a predominantly carbohydrate diet with symptoms of vitamin and protein deficiency. Such patients are often bothered by pain in the upper abdomen associated with concomitant gastritis. pancreatitis or peptic ulcer. Folate deficiency causes reversible anemia of the megaloblastic type, often combined with leukemia and thrombocytopenia. There may be a decrease in adaptation to darkness due to vitamin A deficiency. Hypogonadism with feminization, impotence and testicular atrophy caused by direct toxic effect alcohol on the gonads due to insufficiency of vitamins A and E.

Alcoholism is also accompanied by frequent infectious diseases and osteoporosis. acute or chronic alcoholic myopathy.

The stigmata of alcoholism include Dupuytren's contracture, hypertrophy of the parotid salivary glands, gouty arthropathy. alcoholic polyneuritis.

Such patients are characterized by a puffy face, scleral injection, atrophy of the tongue papillae, loose bleeding gums, rosacea, tremor of the tongue and fingers.

Meet and characteristic changes behavioral reactions: euphoria, familiarity or mental depression. It should be noted that the entire set of above is by no means necessary; many patients have a quite decent appearance.

The symptoms of chronic alcoholic hepatitis itself include a feeling of heaviness and fullness in the right hypochondrium and epigastric region. . bloating, intolerance to fatty foods.

Some patients are concerned pain syndrome, in some patients, after long-term drinking bouts, the appearance of acute painful attacks resembling hepatic colic is possible.

An objective examination reveals moderate hepatomegaly, the liver has a densely elastic or doughy (due to concomitant fatty degeneration) consistency with a smooth surface and a rounded edge, the spleen, as a rule, is not enlarged.

When studying laboratory parameters, hyperaminotransferasemia is determined; 30% of patients have hyperlipidemia, increased IgA content in the blood.

The most characteristic feature of this form of hepatitis is a significant improvement in clinical and laboratory parameters during the abstinence period. Other distinctive features are a relatively low level of aminotransferase activity, thymol test, increased IgA content and the absence of serological markers of viral infection in the blood compared to viral chronic hepatitis.

Toxic and drug-induced chronic hepatitis

They are relatively rare and are usually severe. Drugs can be the cause of almost any symptom of liver damage, and therefore, whenever there are signs of impaired liver function, it is necessary to exclude the drug etiology of these disorders.

Currently, all hepatotoxic drug complications are usually divided into obligate and facultative. Obligate, i.e. mandatory, dose-dependent and reproducible in experimental animals, due to the properties of the chemical compound itself. They are usually relatively harmless, for example, phenobarbital causes hepatomegaly as a result of enzymatic! induction, cortisone - fatty infiltration, etc.

Facultative lesions are unpredictable, do not depend on the dose of drugs and are not reproduced experimentally: they are associated with an individual immune reaction caused by the formation of hepatotoxic metabolites, and are often accompanied by allergic symptoms - fever, rash, adenopathy, eosinophilia.

Most often, after taking certain drugs, liver damage develops, clinically resembling acute viral hepatitis, but without the pre-icteric period.

Chronic active hepatitis and cirrhosis have been described in long-term use tubazide, paracitamol, sulfonamides, nitrofurans, metho-rexate, aldomet. They occur with malaise, jaundice, hepatomegaly, increased activity of alkaline phosphatase and blood aminotransferases, and dysproteinemia.

Chronic nonspecific reactive hepatitis

is the most common chronic inflammatory liver disease. Most authors recommend considering this form not as an independent nosological unit, but as a concomitant symptom indicating the reaction of the liver tissue to an extrahepatic disease, a disease of the liver itself, or long-term exposure to certain environmental and endogenic factors. This explains the double name of this form of hepatitis: nonspecific, i.e. occurring equally with different etiologies, and reactive, i.e. secondary, caused by the liver’s reaction to the underlying disease. The term “hepatitis” in this case is somewhat arbitrary due to the fact that changes in the liver can be caused not only by inflammatory, but also by dystrophic manifestations.

Damage to the liver with its filtration function in relation to various antigens and toxins entering the bloodstream through the portal vein or hepatic artery system.

Nonspecific reactive hepatitis has 4 characteristic features:

secondary nature of the observed changes;

their moderate clinical and laboratory severity;

goodness;

complete reversibility when the factor causing these changes is eliminated.

Nonspecific reactive hepatitis is often observed in patients with peptic ulcers, enterocolitis, pancreatitis, and cholelithiasis. Dyskinesias of the biliary system with omissions of the gastrointestinal tract. Reactive changes in the liver accompany almost 50 different acute and chronic infectious diseases; they appear when damaged by chemicals, burns, and after surgery. Liver enlargement is described in patients with cancer, tuberculosis, collagenosis, and intoxication syndrome of various etiologies.

Such patients complain of malaise, pain, heaviness in the right hypochondrium. Moderate enlargement and tenderness of the liver is possible. Laboratory indicators may be within normal limits or, in some cases, there is a moderate increase (activity of aminotransferases and alkaline phosphatease, an increase in bilirubin with an increase in direct and indirect fractions. Increased concentration of α- or β-glrbulins, depending on the etiology.

Chronic cholestatic hepatitis

It can rightfully be considered when describing almost all forms of chronic hepatitis due to the fact that all of them can occur with prevailing cholestasis syndromes.

The most common and characteristic sign of cholestasis is itchy skin which is observed in all patients with chronic cholestatic hepatitis, regardless of its ethnology. Itching is not coped with symptomatic medications and is often accompanied by painful insomnia. It is combined with icteric staining of the sclera and skin, but may precede the development of jaundice, appearing several months and sometimes years before its manifestation.

Jaundice with cholestatic hepatitis develops slowly. Half of the patients have a brightly icteric coloration of the skin, while some develop generalized skin pigmentation associated with the deposition of melanin. Darkening of the urine and lightening of the stool may occur.

Xanthelasmas are flat, moderately raised above the surface of the skin, soft formations on the palms, back, extensor surface of the elbows, and buttocks, detected in 30% of patients. Xanthelasmas are a criterion for hypercholesterolemia; with cholesterol levels above 12 mmol/l, they occur after 2-3 months, and with hypercholesterolemia exceeding 7.8 mmol/l, after a year.

Extrahepatic signs are always isolated and are observed only in some patients. Hepatomegaly is usually minor, the liver is enlarged by 2-3 cm, dense, with a smooth edge. Splenomegaly, as a rule, is expressed very modestly and is observed during exacerbation of the process.

Laboratory studies reveal cholestasis syndrome - increased activity of alkaline phosphatase, direct siderbilirubinemia, hypercholesterolemia. Less than half of the patients have an increase in thymol test and γ-globulins; low, unstable aminograsferasemia.

TREATMENT.

One of the important factors determining the positive effect of the therapy chronic hepatitis Regardless of its etiology, compliance with the regime is important.

First of all, physical and mental peace must be ensured. In case of exacerbation of the process, bed rest is recommended, creating favorable conditions for increasing hepatic blood flow.

Dietary nutrition is prescribed, table No. 5, with limited consumption of fatty, extractive, salty and smoked foods, with a sufficient amount of fluid, if there is no ascites. Food should be rich or even oversaturated with vitamins.

Work in recent years shows that even with severe liver diseases, during regeneration it is possible to restore its normal structure, which promotes recovery, without the active use of various medications.

TREATMENT OF CHRONIC PERSISTENT HEPATITIS

Due to favorable prognosis Such patients most often do not require specific drug therapy. However, given the unpredictability of the clinical course of this nosological form and the possibility of transition to active hepatitis, it is necessary to carry out courses of maintenance therapy with the drugs listed below, using them in combination or giving preference to one of the groups, based on the principle of an individual therapeutic approach.

First of all, these are vitamins; they can be used enterally or parenterally. Daily doses: vitamin B1 – 5-15 mg, vitamin B6 – 50-120 mg, vitamin B12 – 200 mcg. B vitamins have anabolic activity and take part in carbohydrate, fat and protein metabolism. All of the above vitamins are not recommended to be administered in one syringe due to the presence of cobalt ion in the composition of cyanocobalamin, which contributes to the destruction of other vitamins. Vitamins C and folic acid(daily dose – 15-20 mg).

Vitamin E actively inhibits the processes of lipid peroxidation and the formation of free radicals involved in cytolysis syndrome; it is prescribed one capsule 2-3 times a day (20-30 days).

Good long-term experience has been gained in the treatment of cocarboxylase, which is a coenzyme of a number of enzymes, due to which it has positive influence to all parts of intrahepatic metabolism. Daily dose 50-100 mg.

Lipoic acid – regulates lipid and carbohydrate metabolism, reduces fatty infiltration of the liver. Prescribed orally at 0.025-0.05 g, 3 times a day.

Riboxin is a precursor of ATP, stimulates the synthesis of nucleotides, increases the activity of Krebs cycle enzymes. Used orally, 2 tablets 0.2 g 3 times a day for a month or intravenously, 10 ml of 2% solution 1-2 times a day No. 10-12.

Hepatoprotectors also play an important role; in particular, the drug Essentiale, used intravenously and per Os, is popular. It is a membrane protector based on essential phospholipids. The drug improves the functional state of hepatocytes, strengthens cell membranes and their organelles. Available in ampoules and capsules, 5 ml (250 mg) - 10 ml (1000 mg) are administered intravenously on the patient’s blood, after 2 weeks it is prescribed in capsules 2-3 times a day, for a long period of 2-3 months, if there are no symptoms of cholestasis.

Silymarin (Legalon, Karsil) is a hepatoprotector that improves metabolic processes, used in the form of 35 or 70 mg tablets. The mechanism of action is similar to the domestic drug plant origin– Selibor 40 mg 3 times a day for 3-6 months.

The group of hepatoprotectors includes catergen, which is an antioxidant. It blocks lipid peroxidation, binds free radicals, and normalizes the function of hepatocyte lysosomes.

The group of protein-free liver hydrolysates (sirepar, progepar, ripazone), which are injected into the muscle at a dose of 5 ml/day, No. 30, deserves special attention. They cause regeneration of the liver parenchyma, eliminate hepatic hypoxia, but they are not recommended to be taken during an active process.

There is a point of view whose supporters recommend that patients with chronic persistent and active hepatitis limit as much as possible the intake of medications that contribute to the development of hepatocyte degeneration, inflammatory and fibrotic reactions. They oppose the use of choleretic drugs, liver extracts, the use of mineral waters, and detoxification therapy. It is believed that essentiale, sire-par, and legal do not reduce inflammatory activity, and in some cases can contribute to its increase and the appearance of cholestasis.

We are in slightly different positions and consider preventive and anti-relapse active treatment of chronic hepatitis to be appropriate.

Treatment of active chronic hepatitis of viral etiology

First of all, it is necessary to start with etiological therapy, in particular, treatment of viral hepatitis B with α-interferon, which is used in the replication phase. In particular, intron-A (recombinant α-interferon-2b) and reaferon, roferon (recombinant α-interferon-2b) are used. interferon-2a). Antiviral therapy shortens the duration of the replication phase, leading to... helps eradicate the virus and prevents the development of cirrhosis.

Intron-A prescribed 5-9 million units three times a week for 4-6 months, subcutaneously or intramuscularly. The criteria for effectiveness are considered to be: disappearance of hepatitis B virus replication markers, normalization of aminotransferase activity, improvement of the histological picture (reduction of infiltration of portal tracts, focal and stepwise necrosis).

An accurate distinction between chronic hepatitis into parenchymal (or epithelial) and interstitial (mesenchymal) is impossible, as with acute forms. Chronic hepatitis often occurs in an anicteric form or only periodically gives exacerbations in the form of jaundice, when it is usually more certain to speak about the predominance of parenchymal lesions.

Often, along with the stroma of the organ, reticuloendothelial tissue is predominantly affected, as, for example, in chronic malarial, brucellosis hepatitis, hepatitis in subacute septic endocarditis, etc. Among chronic hepatitis, as well as among acute ones, focal hepatitis is also distinguished , for example, with gummous syphilis with a predominant perivascular location of specific infiltrates, healing with partial scarring (organ fibrosis).

The term “chronic hepatitis” refers to the presence of inflammation, necrosis and fibrosis of liver tissue. The causes of chronic hepatitis are varied. The course of the disease and the effectiveness of treatment depend on the etiology of hepatitis, age and condition of the patient. However, the final stage of any form of chronic hepatitis is cirrhosis of the liver, and its complications are the same regardless of the cause of hepatitis.

Hepatitis B is a serious occupational risk for healthcare workers.

Frequency. Chronic hepatitis occurs with a frequency of 50-60 cases per 100,000 population, predominantly affecting men. The prevalence of HBV in Russia reaches 7%. The prevalence of CHC is 0.5-2%.

Classification. According to etiology, chronic hepatitis is distinguished: viral B; viral D; viral C; viral, unspecified; autoimmune; alcoholic; drug; due to primary biliary cirrhosis; due to primary sclerosing cholangitis; due to Wilson's disease; due to α-antitrypsin deficiency; rective.

Forms of chronic hepatitis

There are three histological forms of chronic hepatitis:

Chronic hepatitis C minimal activity- a mild disease in which inflammatory process limited to portal tracts. Serum aminotransferase activity may be close to normal or moderately increased.
Chronic active hepatitis is a disease that occurs with a detailed clinical picture, in which liver function indicators and histological picture correspond to active inflammation, necrosis and fibrosis. Histological examination reveals active inflammation of the parenchyma outside the portal tracts, stepwise necrosis and fibrosis.
In chronic lobular hepatitis, inflammatory infiltration of the hepatic lobules with isolated foci of necrosis is detected.

Histological classification emphasizes the importance of liver biopsy for diagnosis, treatment and prognosis. For each cause of hepatitis, any of the described histological forms of the disease is possible, so histological examination alone is not enough to make a diagnosis and select the appropriate treatment.

Causes of chronic hepatitis

The causes of chronic hepatitis can be divided into several main groups: viral hepatitis, metabolic disorders, autoimmune and drug-induced hepatitis.

Various infections, collagen diseases, transition acute hepatitis in chronic, excessive and poor nutrition, exposure to hepatotropic poisons, hepatotropic medications.

Chronic hepatitis, leading to significant changes in the structure of the organ, can be considered as precirrhotic diseases; however, it should be emphasized that in a normal liver there are significant amounts of parenchyma reserve, the great ability of liver tissue to regenerate and the significant reversibility of even long-term hepatitis, which does not allow identifying chronic hepatitis with the irreversible final stage of their liver cirrhosis. Indeed, in the clinic one can often observe how, even with many years of liver enlargement during a protracted course of brucellosis or with repeated diseases of malaria, subsequently, with the cure of the main suffering, a complete clinical recovery occurs with the return of the size and function of the liver to normal.

Hepatitis A and E viruses are not able to persist and lead to chronic forms hepatitis A. For other viruses, there is not enough information about the possibility of chronic inflammation.

The incubation period of HCV is 15-150 days.

Pathogenesis

The development of hepatitis B begins with the introduction of the pathogen into the body or infection. Lymphocytes produce antibodies. As a result, immune complex damage often occurs various organs and systems. With the development of pronounced immunity, the virus is suppressed and recovery occurs.

The development of autoimmune hepatitis is often preceded by bacterial or viral infection. A T-cell immune response occurs with the formation of antibodies to self-antigens and tissue damage as a result of inflammation. The second mechanism of autoimmune damage is associated with molecular mimicry, caused by the similarity of cell antigens with the antigen of the herpes simplex virus. Antinuclear (ANA), anti-smooth muscle (SMA/AAA) and other antibodies that damage tissue are formed.

When consuming more than 20-40 g of alcohol per day for men and up to 20 g for women, considered the maximum permissible dose, alcohol entering the liver interacts with the enzyme alcohol dehydrogenase to form toxic acetaldehyde and other aldehydes. Another operating mechanism- microsomal oxidation of ethanol - leads to the formation active forms oxygen, which also damages the liver. Macrophages entering the liver during inflammation produce cytokines, including TNF-a, which aggravate damage to the organ. Many are violated chemical reactions in the liver, including fat metabolism, methionine metabolism with a decrease in methionine adenosyltransferase activity, release of homocysteine, which stimulates liver fibrosis.

In non-alcoholic steatohepatitis, hepatocyte apoptosis accelerates and the level of circulating TNF- increases; There is an increase in lysosome permeability and the release of cathepsins, dysfunction of cell mitochondria, which induce β-oxidation in mitochondria with activation of oxidative stress.

Symptoms and signs of chronic hepatitis

Dyspeptic complaints after eating, sometimes mild jaundice with a moderate increase in direct bilirubin in the blood. The course is slow (long-term, persistent chronic hepatitis) or rapidly progressive (active chronic hepatitis). Moderate violation functional capacity of the liver. Shifts in the protein spectrum of the blood (increase in α 2 - and γ- globulins in the blood). Often relapsing course. Hypersplenism and intrahepatic cholestasis may occur. According to radioisotope scanning data, paint absorption appears to be moderately diffusely reduced (normally there is dense, uniform shading, indicating a high degree of absorption of labeled compounds).

Clinically, chronic hepatitis is manifested mainly by liver enlargement varying degrees, usually uniform or with a predominance of one, usually the left, lobe. The liver is dense to the touch, can be sensitive and even painful in the presence of pericholecystitis; At the same time, there may be independent pain. Jaundice is usually observed only periodically, with exacerbations of the process, and less often it can take a protracted course. With severe jaundice, skin itching and other phenomena characteristic of severe parenchymal jaundice develop. More often, in chronic hepatitis, only subictericity of the sclera and skin is found. Liver function outside of exacerbations of jaundice is usually slightly impaired, or this disorder is detected only by deviations from the norm in one or two more sensitive liver tests. The spleen is often enlarged.

With mesenchymal hepatitis, symptoms of the underlying disease are usually observed (brucellosis, subacute septic endocarditis, collagen diseases, malaria, etc.). Hepatomegaly or hepatolienal syndrome is possible. The function of the organ is not significantly impaired.

Manifestations of liver damage are more typical for hepatocellular, especially active (recurrent or aggressive) forms of chronic hepatitis. They are accompanied by pain in the right hypochondrium, dyspepsia, enlargement of the liver and sometimes the spleen, “spider veins” may occur, and during exacerbations - yellowness of the sclera and skin, and are characterized by a greater or lesser degree of dysfunction.

Chronic hepatitis can progress (continuously or in waves) - with the transition to liver cirrhosis, take a stationary (persistent) course, or regress.

Considering the importance of the liver in performing many metabolic functions, clinical syndromes Liver damage in chronic hepatitis is very diverse.

Asthenovegetative syndrome, or “liver laziness syndrome.”
Dyspeptic syndrome.
Pain syndrome with hepatitis.
Hepatomegaly. Common sign HG.
Jaundice. An increase in conjugated bilirubin indicates a high activity of the process, this is a sign of disease progression (necrosis of hepatocytes).
Hemorrhagic syndrome in chronic hepatitis is associated with hepatic cellular failure (clotting factors are not synthesized) or the development of vasculitis, indicating the systemic nature of the lesion and the inclusion of antigen-antibody immune reactions.
Skin itching. If it is the leading syndrome, then this indicates cholestasis. The screening test is alkaline phosphatase (ALP).
Lymphadenopathy in chronic hepatitis.
Fever.
Edema-ascitic syndrome. This is a complication of portal hypertension.
Endocrine disorders in chronic hepatitis.

Superinfection with the hepatitis D virus, even against the background of a sluggish HBV process, causes progression of the disease. Rarely, this causes fulminant hepatitis.

Diagnosis of chronic hepatitis

A carefully collected anamnesis and examination allow us to diagnose correct diagnosis. Difficulties arise in cases of prolonged acute hepatitis. Timely diagnosis of transition acute course diseases into chronic ones are facilitated by polarographic analysis of blood serum. To establish the morphological direction, activity of the process, solve differential diagnostic problems (fatty liver, early cirrhosis, amyloid, congenital hyperbilirubinemia, etc.), especially great importance has a needle biopsy of the liver.

The diagnosis of chronic hepatitis should be made taking into account the possibility of other causes of enlargement or changes in the borders of the liver. At differential diagnosis The following forms must be excluded in particular:

Stagnant (nutmeg) liver, which is generally the most common cause liver enlargement in the clinic is often mistaken for an inflammatory process or tumor.
Amyloid liver and fatty liver, representing a degenerative-infiltrative rather than inflammatory process. The amyloid liver rarely reaches a significant size and is easily recognized, especially in the presence of amyloid nephrosis, the most common localization of amyloidosis. Fatty liver in many cases it is not recognized intravitally, although it is of great importance as a precirrhotic disease, occurring especially often in caseous tuberculosis with ulcerative lesion intestines and various general dystrophies. This prognostically severe form of liver damage is characterized by edema, severe hypoproteinemia, and decreased body resistance. various infections and other harmful things. When treating fatty liver, it is especially important to introduce so-called lipotropic substances, for example, lipocaic substance isolated from the pancreas, some amino acids, vitamins, as well as the administration of liver preparations, along with a complete protein diet. Persistent liver therapy is apparently of great importance for the treatment of amyloid degeneration of the organ.
Hepato-cholecystitis, when in the presence of cholecystitis, damage to the liver itself predominates due to active hyperemia, stagnation of bile or ascending infection. Cholecysto-hepatitis is spoken of when predominant defeat biliary tract and less reactive process on the part of the liver itself.
Active liver hyperemia in alcoholics, in diabetic patients, as well as in cases of liver irritation in cases of colitis, intestinal stasis often represents the initial stage of inflammatory hepatitis; when carrying out persistent treatment of metabolic disorders, including balneological, or intestinal disorders liver enlargement is largely reversible.
Liver prolapse can be mixed with chronic hepatitis, if you do not pay attention to the fact that with this form bottom line the liver is located obliquely and is even higher than normal midline and left costal margin.

Liver prolapse is found in women with careful examination in 4-5% and much less often in men (Kernig).

Laboratory diagnosis of hepatitis is based on the detection of cytolysis syndrome, accompanied by damage to hepatocytes and the release of ALT, AST, GGTP, ALP enzymes into the blood, the activity of which increases, and an increase in bilirubin levels.

An ultrasound scan of the liver, pancreas, spleen, and portal vein is performed. The ultrasound picture of chronic hepatitis is characterized by signs of diffuse liver damage, especially increased echo density.

If virus markers are detected, confirmatory testing is carried out qualitative research for the presence of viral DNA: HV-B DNA (qualitative) and/or HV-C RNA (qualitative).

When the presence of chronic viral hepatitis is confirmed, tests are performed to identify replication markers in order to clarify the severity of the process.

At each stage of viral hepatitis, it is possible to study a number of other antigens, antibodies and other sources, but this is rarely necessary.

Autoimmune hepatitis can be diagnosed when, in addition to increased ALAT and AST, hypergammaglobulinemia and autoantibodies in the blood serum are noted. The most common (85% of all cases) is the 1st subtype - classic autoimmune hepatitis, in which antibodies ANA - antinuclear, AMA - antimitochondrial, LMA - antiliposomal are detected. In the 3rd subtype, SMA antibodies are detected - anti-smooth muscle.

Non-alcoholic steatohepatitis often develops in patients with overweight body and obesity. Disorders of lipid metabolism, often hyperinsulinemia, are detected. These patients very often develop hepatic steatosis. Non-invasive diagnostic methods are used using the FibroMax and Fibro-Meter tests to detect fibrosis and cirrhosis.

Drug-induced hepatitis accounts for 15-20% of fulminant hepatitis in Western Europe, and 5% in Russia. More often they occur in older women when combining several drugs due to their drug interactions(for example, when general metabolism through cytochrome P450), for diseases of the liver and kidneys. Toxic liver damage, depending on the dose of the drug, can be caused by paracetamol, aspirin, nimesulide, amiodarone, estrogens, semisynthetic penicillins, cytostatics, and very rarely statins. Idiosyncratic liver damage is caused by increased sensitivity, often genetically determined. Substances can act as haptens, causing the formation of antigens to hepatocytes.

Differential diagnosis. Differential diagnosis in case of liver damage, it is most often carried out according to the syndromes of jaundice and hepatomegaly.

There are three types of jaundice: hemolytic (suprahepatic), parenchymal (hepatic) and mechanical (subhepatic).

At hemolytic jaundice A triad of signs is identified: anemia, jaundice and splenomegaly. The number of reticulocytes in the blood is increased, indicating activation bone marrow. Hemolytic anemia divided into congenital and acquired (autoimmune).

Hepatic jaundice is divided into a predominance of unconjugated and conjugated bilirubin.

An increase in unconjugated bilirubin in the blood can be observed with Gilbert's syndrome. Occurs in 1-5% of the population. Jaundice is caused by a violation of the transport of bilirubin into the hepatocyte, and therefore its conjugation with glucuronic acid is disrupted. Periodic episodes of jaundice may occur with childhood. Asthenia is characteristic. Liver functions are not impaired. Treatment with phenobarbital eliminates jaundice.

Mechanical, or obstructive, jaundice is most often caused by compression of the biliary tract by a stone or tumor. The skin color gradually changes from yellowish to greenish-yellow. Characterized by persistent itching of the skin and multiple scratches. The disease is confirmed by ultrasound and CT scanning, which reveal dilated bile ducts.

Hepatomegaly syndrome (liver enlargement) is observed in many diseases:

heart failure;
acute viral, drug-induced, alcoholic hepatitis;
chronic hepatitis;
cirrhosis of the liver;
liver tumors;
polycystic liver disease;
portal vein thrombosis;
infiltrative processes (amyloidosis, hemochromatosis), etc.

It should be noted the importance of assessing the duration of hepatitis: when the process lasts up to 6 months, it is considered acute, and beyond this period - as chronic hepatitis.

Treatment of chronic hepatitis

Treatment of chronic hepatitis is carried out as follows: specific therapy, and through pathogenetic, including dietary, treatment of liver damage as such according to the principles set out in the treatment of Botkin’s disease.

A complete diet (during an exacerbation, it is carried out against the background of bed rest), rich in carbohydrates, proteins, vitamins, mineral salts and electrolytes - diet No. 5. Vitamin therapy: intramuscular vitamin B 1, 1 ml of 5% solution, vitamin B 6, 1 ml 5 % solution, vitamin B 12 100 mcg intramuscularly every other day, a total of 15 injections, 10-20-40% glucose solution 20-40 ml along with 5 ml of 5% ascorbic acid solution intravenously. During remission Spa treatment in Essentuki, Zheleznovodsk, Pyatigorsk, Borjomi, Morshyn, Truskavets, Druskininkai.

Outside of exacerbation - mostly gentle treatment, rational employment, complete diet, rich in proteins, carbohydrates and vitamins. During periods of exacerbation - bed rest, B vitamins, liver extracts (campolon, sirepar, vitohepat), for active (aggressive) chronic hepatitis - glucocorticoids c. combination with anabolic hormones dianabol, nerobol) and immunosuppressants, especially if corticosteroids have no effect. Hormone therapy(for example, prednisolone 30-40 mg daily with a gradual dose reduction by an average of 5 mg per week) is carried out for a long time, sometimes for many months (on average 2-3 months), if necessary, repeated courses. Patients are subject to dispensary observation. In case of stable remission, sanatorium-resort treatment is indicated (Essentuki, Pyatigorsk, Zheleznovodsk, etc.).

Diet therapy is an important component of the treatment of chronic hepatitis. Preferably 4-5 meals a day. They recommend a sufficient amount of protein contained in dairy products, fish, and meat; fruits and vegetables, rice, oatmeal, semolina and buckwheat porridge- sources vegetable fiber; from fats - vegetable and dairy, which have a lipotropic effect, as well as products containing vitamins A, C, group B. Refractory fats and products with high content fats, rich broths, fried foods, hot seasonings.

For autoimmune hepatitis, glucocorticosteroids (GCS) are used: prednisolone. As an alternative, the cytostatic drug azathioprine can be used.

For the treatment of chronic hepatitis and toxic liver damage, hepatoprotectors are used:

milk thistle preparations: legalon, karsil, silymar; including combination drug hepabene;
preparations with flavonoids of other plants: Liv 52, artichoke (chophytol), pumpkin seed oil (tykvenol);
essential phospholipids: essentiale, essentiale, phosphogliv;
ornithine aspartate (hepamerz);
drugs with an indirect detoxifying effect: reducing the formation of toxins: lactulose (Duphalac); activating the formation of endogenous detoxicants: ademetionine (heptral); accelerating the metabolism of toxicants: metadoxyl, phenobarbital; excreting toxic bile acids: ursodeoxycholic acid (ursosan).

For alcoholic liver damage, adeomethionine (Heptral) is used; for encephalopathy - ornithine (Hepamerz) orally.

Ursodeoxycholic acid (ursosan, ursofalk, ursodez) showed high efficiency with toxic liver damage, non-alcoholic steatohepatitis, increased ALAT, AST while taking statins.

Chronic viral hepatitis D

Pathogenesis. The D virus has a cytopathogenic effect on hepatocytes.

Symptoms. The disease is characterized severe course With pronounced symptom hepatic cell failure (weakness, drowsiness, bleeding, etc.). A significant proportion of patients develop jaundice and itchy skin. Physically, hepatomegaly, splenomegaly with hypersplenism, edematous-ascitic syndrome and early development liver cirrhosis.

Laboratory tests: severe dysproteinemia - hypoalbuminemia and hypergammaglobulinemia, increased ESR, 5-10-fold increase in ALT and bilirubin levels. Virus markers - HDV RNA and anti-HDV IgM class; integration markers - HBsAg and anti-HBe.

Chronic viral hepatitis C

Symptoms. There is a moderately pronounced asthenic syndrome and hepatomegaly. The course is undulating, with episodes of deterioration, with hemorrhagic manifestations and long-term increase ALT level. Liver cirrhosis develops after decades in 20-40% of patients. Markers - RNA virus and antibodies to it (anti-HCV).

Treatment. Outside the acute phase, treatment consists of following a diet. In the acute phase, bed rest (increases blood flow in the liver), detoxification measures (glucose, hemodez intravenously), vitamins B1, B2, B12, E, C, hepatoprotectors (heptral, hofitol, essentiale, karsil, etc.), lactulose (duphalac) are indicated ). In order to eliminate or stop the replication of the virus, antiviral therapy with interferon is carried out. However, there is no convincing evidence that interferon prevents disease progression, the development of cirrhosis, or reduces mortality. Currently, therapy with interferon alpha is being replaced by complex antiviral therapy, consisting of pegylated interferon with prolonged action and ribavirin. Liver transplantation is usually contraindicated.

Autoimmune hepatitis

Traditionally, there are two types of autoimmune hepatitis. Type 1, the most common, is characterized by the presence of antinuclear antibodies and autoantibodies to the smooth muscle elements of the liver (70-100%).

A clear connection has been identified with HLA, DR3 alleles (the disease usually begins in at a young age, severe course) and DR4 (hepatitis begins at an older age and is characterized by a more benign course).

Symptoms. Mostly women aged 10-30 years or older than 50 years are affected (the ratio of women to men is 8:1). The onset is gradual with asthenia, malaise, pain in the right hypochondrium. In 30% of patients, the disease begins suddenly with the development of jaundice, increased activity aminotransferases. Signs of chronic liver damage appear: skin telangiectasia, palmar erythema, stretch marks on the thighs and abdominal wall. Physically: the liver is dense with a predominant increase in the left lobe, splenomegaly, polyarthritis large joints, erythema, purpura, pleurisy, lymphadenopathy.

In 48% of cases others make themselves known autoimmune processes: thyroid diseases, arthritis, vitiligo, ulcerative colitis, diabetes, lichen planus, alopecia, mixed disease connective tissue.

Laboratory tests: moderate pancytoenia, a noticeable increase in ESR and AST levels (2-20 times), which reflects the degree of inflammatory changes in the liver; hyperproteinemia (90-100 g/l or more), hypergammaglobulinemia. In 30-80% of cases, HLA-DR3, DR4 is detected; determination of autoantibodies (see above).

Treatment. It is carried out with prednisolone in an initial dose of 20-40 mg/day under the control of AST activity. A combination of glucocorticoids with azathioprine is useful (and azathioprine allows you to reduce the dose hormonal drug). Moreover, remission remains in more than 80% of patients for 1-10 years. If there is no effect from the therapy described above, it is possible to use new immunosuppressants - tacrolimus, cyclosporine, mycophenolate mofetil, but their true significance is not fully understood. If cirrhosis develops, liver transplantation is indicated.

Alcoholic hepatitis

Alcoholic hepatitis develops in persons who take more than 100 g of vodka per day for women and more than 200 g for men with frequent and long-term use.

Pathogenesis. When drinking alcohol, acetaldehyde (which is a direct liver poison) accumulates with the formation of hepatic lipoprotein and alcoholic hyaline, which attract leukocytes; inflammation forms.

Symptoms. Anicteric and cholestatic (more severe) variants are possible. Characteristic: hepatomegaly with a rounded edge of the liver, dyspeptic and abdominal syndromes, signs of myocardial dystrophy, skin changes, weight loss, Dupuytren's contracture.

Laboratory studies show an increase in the activity of both serum transaminases (mainly AST), gammaglutamyl transpeptidase, alkaline phosphatase, and IgA. The concentration of markers of the acute phase of inflammation (SRV, ferritin) increases. Liver biopsy shows macrovesicular fatty degeneration, diffuse inflammatory reaction to necrosis, and Mallory's alcoholic hyaline.

Treatment. Required complete failure from drinking alcohol. Vitamins Bq, 512, riboflavin, foschic acid and ascorbic acid). Thiamine is prescribed (to prevent Wernicke encephalopathy); prednisolone or methylprednisolone; if necessary, pulse therapy with prednisolone 1000 mg intravenously for 3 days; metadoxyl - 5 ml (300 mg) intravenously drip for 3-5 days or in tablets; pentoxifylline; membrane-stabilizing drugs (heptral, hofitol, essentiale, picamilon, etc.); carry out detoxification therapy (glucose, electrolytes, hemodez).

Chronic reactive hepatitis

Nonspecific reactive hepatitis - secondary lesion liver tissue in some extrahepatic diseases. In essence, this is secondary hepatitis, reflecting the reaction of the liver tissue to big number extrahepatic diseases.

Causes. The causes of reactive hepatitis can be gastrointestinal diseases ( peptic ulcer, pancreatitis, cholecystitis, ulcerative colitis), systemic diseases connective tissue (SLE, RA, scleroderma, polymyositis, etc.), diseases endocrine glands(thyrotoxicosis, diabetes mellitus), more than 50 acute and chronic infections, tumors various localizations before they metastasize to the liver.

Pathomorphology. The histological picture of reactive hepatitis of different etiologies is identical and is characterized by polymorphism of hepatocytes, focal protein and fatty degeneration, and necrosis of single hepatocytes. Morphological changes are moderate, usually do not progress and are completely reversible when the underlying disease is eliminated.

Symptoms. Asymptomatic. There is only a moderate enlargement of the liver. In this case, liver function tests do not change significantly.

Diagnostics. The diagnosis is based on morphological data, moderate hepatomegaly, slight change functional tests liver and taking into account the underlying disease.

Treatment. Consists of therapy and prevention of aggressive effects on the liver (alcohol, etc.).

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

Symptoms:

In a number of patients with CAH of viral etiology, a direct connection with acute viral hepatitis, but in most cases the acute phase of hepatitis and the appearance clinical symptoms Chronic hepatitis is 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, but there is a feeling of heaviness and fullness in the right hypochondrium, independent of food intake; many patients complain of the unpleasant taste of food products.

Dyspeptic syndrome rarely reaches significant severity, constant, painful, 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.