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Viral hepatitis (B15-B19)

If necessary, indicate the cause of post-transfusion hepatitis, use an additional code (Class XX).

Excluded:

• cytomegalovirus hepatitis (B25.1)
• herpes viral hepatitis (B00.8)
• consequences of viral hepatitis (B94.2)

In Russia, the International Classification of Diseases, 10th revision (ICD-10) has been adopted as a single normative document for recording morbidity, reasons for the population's visits to medical institutions of all departments, and causes of death.

ICD-10 was introduced into healthcare practice throughout the Russian Federation in 1999 by order of the Russian Ministry of Health dated May 27, 1997. No. 170

The release of a new revision (ICD-11) is planned by WHO in 2017-2018.

With changes and additions from WHO.

Processing and translation of changes © mkb-10.com

Source: http://mkb-10.com/index.php?pid=531

Classification of hepatitis according to ICD-10 - disease codes

As a rule, hepatitis (ICD-10 code depends on the pathogen and is classified in the range B15-B19), which is a polyetiological inflammatory disease of the liver, is of viral origin. Today, in the structure of pathologies of this organ, viral hepatitis takes first place in the world. Infectious disease hepatologists treat this disease.

Etiology of hepatitis

The classification of the disease is complex. Hepatitis is divided into 2 large groups according to the etiological factor. These are non-viral and viral pathologies. The acute form includes several clinical variants with different causes.

In practice, the following types of non-viral disease are distinguished:

1. Inflammatory-necrotic nature has progressive liver damage in the autoimmune variant, that is, if autoimmune hepatitis develops. Your own immunity destroys the liver.
2. Due to prolonged irradiation at doses of more than 300–500 rad over 3–4 months, a radiation variant of inflammation of the liver tissue develops.
3. Necrosis often occurs with toxic hepatitis (ICD-10 code K71). The cholestatic type, a very severe liver disease, is associated with problems with bile excretion.
4. In the structure of this pathology, unspecified hepatitis is determined. This disease develops unnoticed. This is a disease that has not evolved into cirrhosis of the liver. It also does not complete within 6 months.
5. Against the background of infectious diseases and gastrointestinal pathologies, damage to liver cells of an inflammatory-dystrophic nature develops. This is reactive hepatitis (ICD code K75.2).
6. Toxic jaundice is divided into the medicinal or alcoholic form, which occurs as a result of the abuse of harmful drinks or medications. Drug-induced or alcoholic hepatitis develops (ICD-10 code K70.1).
7. Cryptogenic hepatitis is considered a disease of unknown etiology. This inflammatory process is localized and rapidly progresses in the liver.
8. The consequence of infection with syphilis and leptospirosis is bacterial inflammation of the liver tissue.

Diseases of viral origin

At the moment, the etiology of each of these pathogens is being studied in detail. In each type of disease, genotypes - subtypes of viruses - were found. Each of them always has its own distinctive features.

Viruses A and E are the least dangerous. Such infectious agents are transmitted through contaminated drink and food, and dirty hands. A month or a month and a half is the recovery period for these types of jaundice. The greatest danger is caused by viruses B and C. These insidious pathogens of jaundice are transmitted sexually, but more often through blood.

This leads to the development of severe chronic hepatitis B (ICD-10 code B18.1). Jaundice C of viral origin (CVCV) often develops asymptomatically up to 15 years of age. The destructive process gradually occurs in the body of a patient with chronic hepatitis C (ICD code B18.2). Unspecified hepatitis lasts for at least six months.

If a pathological inflammatory process develops for more than 6 months, a chronic form of the disease is diagnosed. At the same time, the clinical picture is not always clearly expressed. Chronic viral hepatitis occurs gradually. This form often leads to the development of cirrhosis of the liver if not properly treated. The patient's organ is enlarged and pain is observed.

Mechanism and symptoms of disease development

The main multifunctional cells of the liver are hepatocytes, which play a major role in the functioning of this exocrine gland. They become the target of hepatitis viruses and are affected by the causative agents of the disease. Functional and anatomical liver damage develops. This leads to severe disorders in the patient’s body.

A rapidly developing pathological process is acute hepatitis, which is in the international classification of diseases of the tenth revision under the following codes:

• acute form A - B15;
• acute form B - B16;
• acute form C - B17.1;
• acute form E - B17.2.

Blood tests show high levels of liver enzymes and bilirubin. In short periods of time, jaundice appears, and the patient develops signs of intoxication of the body. The disease ends with recovery or chronicity of the process.

Clinical manifestations of the acute form of the disease:

1. Hepatolienal syndrome. The spleen and liver quickly increase in size.
2. Hemorrhagic syndrome. Due to disruption of homeostasis, increased vascular bleeding develops.
3. Dyspeptic phenomena. These problems are manifested by digestive disorders.
4. The color of urine and feces changes. The stool is characterized by a grayish-white color. Urine becomes dark. The mucous membranes and skin acquire a yellow tint. In the icteric or anicteric variant, a form of acute hepatitis may occur, which is considered typical.
5. Asthenic syndrome gradually develops. This is emotional instability, increased fatigue.

The danger of viral jaundice

Of all the pathologies of the hepatobiliary system, the development of liver cancer or cirrhosis most often results from the viral type of the disease.

Due to the risk of the latter, hepatitis poses a particular danger. Treatment of these pathologies is extremely difficult. Death in the case of viral hepatitis is often observed.

Diagnostic tests

Establishing the causative agent of the pathology and identifying the cause of the development of the disease are the goals of the examination.

Diagnostics includes the following list of procedures:

1. Morphological studies. Needle biopsy. A thin hollow needle is used to puncture the tissue in order to examine biopsy samples.
2. Instrumental tests: MRI, ultrasound, CT. Laboratory tests: serological tests, liver tests.

Therapeutic methods of influence

Experts, based on the results of a diagnostic examination, prescribe conservative treatment. Specific etiological therapy is aimed at eliminating the causes of the disease. In order to neutralize toxic substances, detoxification is mandatory.

Antihistamines are indicated for various types of illness. Diet therapy is required. A balanced, gentle diet is necessary for hepatitis.

At the first signs of trouble, it is important to promptly contact an experienced specialist.

Source: http://ogepatite.ru/vidy/kod-po-mkb-10.html

Acute and chronic viral hepatitis

Chronic viral hepatitis (CVH) is a chronic inflammation of the liver caused by hepatotropic viruses, which continues without a tendency to improve for at least 6 months.

The vast majority of cases of chronic hepatitis are caused by hepatitis viruses B, C and D. The role of other hepatotropic viruses (virus G, TTV, SEN, etc.) has not yet been fully studied.

B18 Chronic hepatitis

B18.0 Chronic viral hepatitis B with delta agent

B18.1 Chronic viral hepatitis B without delta agent

B18.2 Chronic viral hepatitis C

B18.8 Other chronic viral hepatitis

B18.9 Chronic viral hepatitis, unspecified.

Abbreviations: HBV - hepatitis B virus; HCV - hepatitis C virus; HDV - hepatitis D virus.

EXAMPLE OF FORMULATION OF DIAGNOSIS

In the absence of morphological study data, it is possible to assess the activity of the process based on the severity of cytolysis syndrome (see section “Classification”).

Hepatitis B is one of the most common infections. There are approximately 300 million patients with chronic hepatitis B in the world (approximately 5% of the entire population). Every year, at least people die from liver damage associated with HBV infection (ninth place in the structure of overall mortality). The prevalence of HBV infection varies significantly in individual countries.

■ Regions with low prevalence (up to 2% of the population) include the USA, Canada, Western European countries, Australia, and New Zealand.

■ Regions with intermediate prevalence (3–5%) include Eastern Europe, Mediterranean countries, Japan, Central Asia and the Middle East, Central and South America.

■ Regions with high prevalence (10–20%) (endemic areas) include South Asia, China, Indonesia, countries of tropical Africa, the Pacific Islands, and Alaska.

The causative agent of HBV infection is a DNA virus from the Hepadnaviridae family. The main route of transmission is parenteral (injection, blood transfusion), as well as through damaged mucous membranes and skin (perinatal, sexual contact). Hepatitis B is characterized by high contagiousness - infection is possible when a negligible amount of infected material (0.0001 ml of blood) comes into contact with damaged skin or mucous membranes. The virus is stable in the external environment; at room temperature it retains its pathogenicity in dried blood for at least 7 days.

The frequency of individual transmission modes varies significantly among different regions. In countries with low prevalence, infection most often occurs through sexual contact and parenteral routes (in risk groups). On the contrary, in countries with medium and especially high prevalence, the leading route of infection is perinatal.

The main HBV Ags are surface (Australian) (HBsAg), core (HBcAg), which is found only in hepatocytes, and a marker of viral replication (HBeAg). HBsAg, HBeAg, antibodies to them and to HBcAg (anti-HBs, anti-HBe, anti-HBc), as well as HBV DNA are the most significant serological markers of hepatitis B (for more details, see the “Diagnostics” section).

According to WHO, there are at least 170 million people infected with HCV in the world. The prevalence of HCV infection also varies significantly in different regions - from 0.01–0.02% in Western Europe to 6.5% in tropical Africa. CHV C is the most common form of chronic liver disease in most European countries and North America. The total number of HCV-infected people in Russia is more than 1 million 700 thousand people. HCV infection is the cause in approximately 40% of cases of chronic liver pathology.

The disease is caused by an RNA virus from the Flaviviridae family. The main route of transmission is parenteral. Sexual and perinatal modes of transmission are also possible, but are of less importance due to the relatively low (compared to HBV) contagiousness of the virus. HCV is genetically heterogeneous - there are 6 main genotypes (1–6) and at least 50 subtypes. On the territory of the Russian Federation, the most common genotypes are 1b and 3a.

The genotype of the virus is of fundamental importance for treatment: the effectiveness of antiviral drugs is significantly lower for infections associated with genotype 1 (no more than 50%) compared to genotypes 2 and 3 (up to 80–90%).

The main serological markers of hepatitis C are antibodies to HCV Ag (anti-HCV) and viral RNA.

HDV infection is most common in Southern Europe, North Africa, the Middle East, and Central and South America; in some regions its prevalence can reach 47%. There are approximately 15 million patients with hepatitis D in the world. The frequency of HDV infection in patients with chronic hepatitis B is on average approximately 10% (US data).

The disease is caused by a partial RNA virus (HDV, δ virus), which requires HBV for expression and pathogenicity. The routes of transmission are similar to those of HBV infection. The disease can occur in the form of an acute infection with simultaneous infection with HBV and δ-virus (co-infection) or an acute infection with HDV infection of HBV carriers or patients with CHV B (superinfection). Hepatitis D is usually severe and is characterized by low effectiveness of specific therapy and a poor prognosis. Serological markers - AT kAg HDV (anti-HDV) and viral RNA.

■ To screen for HBV infection, HBsAg is determined in the blood using ELISA. The study is carried out in the following categories of the population.

✧All pregnant women during their first visit to the doctor. A repeat test (if the results of the first one are negative) is carried out in the third trimester if the woman is at risk. If the results are positive, emergency prevention of infection in the newborn is necessary (see section “Prevention”).

✧In persons at risk group C for HBV infection (however, in at least 30–40% of those ill with acute viral hepatitis B, the presence of any risk factors cannot be established):

– homosexuals and men practicing bisexual sexual relations;

– persons who use intravenous drugs;

– persons who are promiscuous;

– victims of sexual violence;

– patients of hemodialysis departments;

– patients with other sexually transmitted diseases;

– migrants from regions where HBV infection is endemic;

– sexual partners of patients with acute or chronic viral hepatitis B or persons who are in close household contact with them;

– medical workers (as part of annual preventive examinations);

– law enforcement officers;

– persons in prison.

✧In patients with symptoms of acute or chronic hepatitis of unknown etiology or when increased activity of ALT and/or AST is detected in the blood serum, not associated with other diseases.

✧Routine screening in the general population is economically justified if the prevalence of HBV infection is 20% or higher.

■ To screen for HCV infection, anti-HCV detection is used using ELISA (the sensitivity of this method reaches 98.8%, specificity - 99.3%).

✧If positive results are obtained, it is necessary to confirm the infection by determining HCV RNA in the blood using PCR. The presence of anti-HCV in the blood in the absence of viral RNA usually indicates that the patient has had the disease in the past. An exception is for patients with immunodeficiency (including those on hemodialysis and after organ transplantation), in whom anti-HCV in the blood may be absent in the presence of HCV RNA.

✧The same categories of population are subject to screening as for HBV infection (with the exception of pregnant women). Since in developed countries the main route of transmission of the disease is parenteral, special attention should be paid to people who use drugs. Approximately 80% of people who share syringes to inject drugs become infected with HCV within 1 year. Moreover, infection is also possible with the use of drugs administered non-parenterally. In particular, cases of HCV infection associated with the use of cocaine and other intranasally administered drugs (using a common inhalation tube) have been described.

■ Routine screening for HDV infection (anti-HDV testing) is not usually carried out, but is possible in persons who have migrated from regions where hepatitis D is endemic.

Specific prevention has been developed only for hepatitis B.

■ Since the main routes of transmission of HBV and HCV in developed countries are parenteral and sexual, measures to prevent drug addiction and promiscuity are of fundamental importance.

■ Blood products and organs for transplantation are subject to mandatory testing for markers of viral hepatitis (and other parenteral infections). To prevent iatrogenic infection, any medical instruments used for invasive therapeutic and diagnostic procedures must be sterilized in accordance with established standards.

■ Health care workers should exercise extreme caution when handling infectious materials (blood and other body fluids) or exposed medical instruments (especially syringes). For any manipulations with potentially infected material, it is necessary to use personal protective equipment (gloves, mask, goggles, etc.). The risk of HBV/HCV infection from a single needle stick used to inject a patient with HBV/HCV infection is 33% and 10%, respectively.

Vaccination against hepatitis B is recommended for all newborns and children under 12 years of age, as well as adolescents and adults at risk B. In the Russian Federation, genetically engineered recombinant vaccines are used for this purpose.

■ All newborns are subject to mandatory vaccination.

✧Newborns born to women with HBV infection must be vaccinated during the first 12 hours of life, while immunoglobulin against human hepatitis B (0.5 ml) is administered; These measures allow in most cases (80–98%) to prevent infectionB. In the absence of specific prophylaxis, the risk of developing HBV infection is very high (from 30 to 90%), and CVH B develops in 90% of cases.

✧In other cases, the first dose is usually administered in the maternity hospital (or during the first 2 months of life), and the second and third 1 and 6 months after the first. Vaccination of newborns is cost-effective and can significantly reduce the incidence of chronic hepatitis B and hepatocellular carcinoma among the pediatric population. It is acceptable to administer hepatitis B vaccine and other vaccines at the same time (but the injection sites must be different).

■ In cases where vaccination was not carried out in the first year of life, it should be carried out before 12 years of age (after this age, the incidence of hepatitis B increases significantly).

■ Adolescents and adults at risk for HBV infection are also required to be vaccinated (see section “Screening”). Before it is carried out, a study on HBsAg and anti-HBs is necessary. If HBsAg or HBsAg and anti-HBs are detected in the blood at diagnostic titers (i.e., signs of HBV infection), vaccination is not indicated. There is also no need for vaccination if only anti-HBs are detected in a protective titer (which indicates that the patient has already suffered acute hepatitis B).

■ Vaccination is also advisable in patients with chronic hepatitis C and other chronic liver diseases, since HBV infection in such cases is severe and has a poor prognosis. However, the effectiveness of vaccination in patients with decompensated liver pathology is quite low.

For children of the first year of life, the vaccine is administered into the anterolateral thigh area, in other cases - into the deltoid muscle. The immunogenicity of the vaccine is lower in obesity, HIV infection, chronic diseases, smoking, and in the elderly. Patients on hemodialysis require large doses. The use of the vaccine is safe and does not lead to the development of neurological complications.

For emergency prevention of HBV infection, immunoglobulin against human hepatitis B and vaccination are used. In case of contact of infected blood with damaged skin or mucous membranes, incidents associated with injections/cuts from infected medical instruments, sexual contact with a patient with HBV infection, immunoglobulin against human hepatitis B (0.06 ml/kg) is administered and a full course of vaccination is carried out. Immunoglobulin and the vaccine can be administered at the same time (but the injection sites must be different). The administration of immunoglobulin should be carried out as soon as possible (no later than 7 days after the incident). If titrant-HBs is more than 10 million IU/ml, you can limit yourself to vaccination only. In case of household contact with a patient with HBV infection, vaccination is also sufficient.

The classification of chronic hepatitis, adopted at the International Congress of Gastroenterologists in Los Angeles (USA) in 1994, is based on the etiological factor with additional information about the activity of the process and the stage of fibrosis (Table 4-7).

Table 4-7. Classification of chronic hepatitis

Chronic viral hepatitis (not otherwise characterized)

Chronic hepatitis not classified as viral or autoimmune

Chronic drug-induced hepatitis

Primary biliary cirrhosis

Primary sclerosing cholangitis

Liver disease caused by α 1 -antitrypsin deficiency

Low (histological activity index 4–8 points)

Moderate (histological activity index 9–12 points)

High (histological activity index 13–18 points)

1 - mild (periportal) fibrosis

2 - moderate fibrosis (porto-portal septa)

3 - severe fibrosis (porto-central septa)

4 - liver cirrhosis

The degree of activity of chronic hepatitis is determined by the results of a histological examination of liver tissue (Knodel system, Table 4-8), as well as by the degree of increase in the activity of ALT and AST: 1.5–2 times more than normal - minimal, 2–5 times - low, 5–10 times - moderate, more than 10 times - pronounced. The stage of fibrosis is determined based on pathomorphological examination of liver biopsies (see Table 4-8).

Table 4-8. Histological activity index (according to Knodell R. et al.) and fibrosis index (according to Sciot J., Desmet V.)

Note: the maximum score (excluding fibrosis) is 18.

Diagnosis of chronic hepatitis B is based on data from a clinical examination of the patient, biochemical blood tests (liver function tests) and testing for serological markers of hepatitis B viruses.

HISTORY AND PHYSICAL EXAMINATION

ACUTE VIRAL HEPATITIS B

■ The duration of the incubation period for acute viral hepatitis B ranges from 30 to 180 days (usually 2–3 months). Depending on the presence and severity of the main symptoms of the disease, typical and atypical (anicteric, subclinical) forms are distinguished.

✧The typical form is characterized by a cyclic course with a sequential change of three periods: the initial (pre-icteric), the height (icteric) and the period of convalescence.

– The pre-icteric period lasts 3–15 days and is characterized by symptoms of intoxication (fever, general weakness, lethargy, apathy, irritability, sleep disturbances, loss of appetite), arthralgia, pain in the right hypochondrium. In some cases, a skin rash (maculopapular, maculopapular, or urticarial) is observed. In the last 1–2 days of the pre-icteric period, stool becomes discolored and urine darkens.

–The icteric period (the height of the period) lasts from 10–14 to 30–40 days. The mucous membranes and sclera, and then the skin, become icteric. With the appearance of jaundice, the symptoms of intoxication usually intensify. In parallel with the increase in jaundice, the liver increases in size. In 30–50% of cases, an enlarged spleen is observed. At the height of the disease, bradycardia, decreased blood pressure, and weakened heart sounds are detected with great constancy. In severe forms, central nervous system depression of varying severity, dyspeptic and hemorrhagic syndromes develop. Separately, a fulminant form is distinguished, caused by massive necrosis of hepatocytes with the development of acute liver failure (frequency - 0.1–0.5%, which is approximately 10% of all cases of acute liver failure).

– The period of convalescence begins from the moment the jaundice disappears and ends after complete clinical and laboratory resolution of the disease, which usually occurs 3 months after its onset (with a prolonged course - after 6 months).

✧In the anicteric form, there is no icterus of the skin and mucous membranes, other symptoms are usually mild.

✧The subclinical form is characterized by a complete absence of clinical manifestations. Diagnosis can only be made on the basis of laboratory tests.

■ The frequency of chronic HBV infection depends on many factors, but most importantly on age and the state of the immune system.

■ Following HBV infection, chronic hepatitis develops in 90% of newborns, 20–50% of children aged 1–5 years, and 5% of adolescents and adults.

■ The risk of chronicity is higher with immunodeficiency of any etiology (patients on hemodialysis, HIV-infected patients receiving immunosuppressive therapy, etc.).

ACUTE VIRAL HEPATITIS C

■ The incubation period is usually 20–90 days. Acute viral hepatitis C is usually mild, predominantly in anicteric or subclinical form. It is diagnosed relatively rarely (no more than 20% of all cases of acute viral hepatitis), mainly in cases where the disease is accompanied by jaundice, or during clinical observation of persons after incidents accompanied by a risk of infection. The most common symptoms are anorexia, nausea, vomiting, discomfort in the right hypochondrium, and sometimes jaundice (in less than 25% of patients). Symptoms usually persist for 2–12 weeks. Fulminant forms of acute viral hepatitis C are observed very rarely.

■ The risk of chronic HCV infection is very high: in more than 80% of patients who have had acute viral hepatitis C, HCV RNA persists in the blood. The risk of developing chronic hepatitis C is slightly lower in children and patients with clinically manifest forms of acute viral hepatitis C.

ACUTE VIRAL HEPATITIS D

Clinical manifestations of coinfection (simultaneous infection with HBV and HDV) are generally identical to those with acute viral hepatitis B. Features include a shorter incubation period, the presence of prolonged fever with a body temperature of 39–41 ° C, frequent appearance of skin rashes and migrating pain in large joints. The course is relatively favorable, the risk of chronicity is practically no higher than that of HBV infection. Acute viral hepatitis D due to superinfection (HDV infection of a person infected with HBV) is rarely observed; it is characterized by a severe course with the frequent development of fulminant forms and a high risk of transformation into chronic hepatitis (up to 90%).

CHRONIC VIRAL HEPATITIS

Clinical manifestations of chronic hepatitis are quite polymorphic and include a wide range of symptoms associated with damage to both the liver and other organs and systems, mainly due to the formation of immune complexes and the development of autoimmune reactions. In many cases, CVH occurs with minimal clinical manifestations or is completely asymptomatic.

■ Dyspeptic syndrome (nausea, worsening after eating and taking drugs, vomiting, bitterness in the mouth, belching, diarrhea) is associated with a violation of the detoxification function of the liver, concomitant pathology of the duodenum, biliary system and pancreas.

■ Asthenic syndrome (weakness, fatigue, decreased performance, irritability, decreased mood) is expressed to a greater or lesser extent in most patients with chronic hepatitis.

■ Signs of liver damage.

✧With an active process, the liver is usually enlarged, hardened and painful.

✧Jaundice (parenchymal) is observed relatively rarely.

✧Telangiectasia and palmar erythema are caused by an increase in estrogen concentration and a change in the sensitivity of vascular receptors (opening and expansion of arteriovenous shunts). Their severity correlates with the activity of the process and does not always indicate cirrhosis of the liver. Improvement in the functional state of the liver is accompanied by a decrease in the number of spider veins or their disappearance; hyperemia of the palms persists much longer (often until biochemical remission).

■ As liver cirrhosis progresses, portal hypertension develops (ascites, splenomegaly, esophageal varices, etc.), and signs of liver failure first appear and intensify (see article “Liver Cirrhosis”).

■ Amenorrhea, gynecomastia, decreased libido are associated with impaired metabolism of sex hormones in the liver (usually at the stage of cirrhosis).

■ Extrahepatic manifestations of CVH B develop quite rarely (in approximately 1% of patients) and are usually represented by kidney damage, polyarteritis nodosa or cryoglobulinemia. Somewhat more often, extrahepatic manifestations develop with CVH C. Possible cryoglobulinemia, membranous glomerulonephritis, porphyria cutanea tarda, autoimmune thyroiditis, less often - Sjögren's syndrome, lichen planus, seronegative arthritis, aplastic anemia, B-cell lymphoma.

■ Clinical blood test: possible increase in ESR, leukopenia, lymphocytosis, and in the fulminant form of acute viral hepatitis - leukocytosis.

■ General urine analysis: with acute viral hepatitis and exacerbation of chronic hepatitis, the appearance of bile pigments, mainly direct bilirubin, urobilin, may appear.

■ Biochemical blood test.

✧Cytolysis syndrome: increased activity of ALT, AST. Characteristic of all clinical variants of acute viral hepatitis and most cases of chronic hepatitis (ALT may be normal in 40% of patients with chronic hepatitis C).

✧Cholestasis syndrome: increased activity of alkaline phosphatase, GGTP, cholesterol content, total bilirubin (due to bound bilirubin). Usually observed with jaundice; it is necessary to exclude other causes of liver damage.

✧Mesenchymal inflammation syndrome: increased immunoglobulin content, increased thymol test, decreased sublimate test. Characteristic of all clinical variants of acute viral hepatitis and exacerbation of chronic hepatitis.

✧Hepatocellular failure syndrome: decreased prothrombin index, serum albumin concentration, cholesterol, increased total bilirubin (due to indirect bilirubin); characteristic of severe forms of acute viral hepatitis and the transformation of chronic hepatitis into liver cirrhosis with the development of liver failure.

■ Markers of hepatitis viruses (Table 4-9).

Table 4-9. Serological markers of HBV infection

* A more correct term is “latent HBV infection.”

✧HBV: HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc IgM, anti-HBc IgG, HBV DNA.

–HBsAg can be detected in the blood 1–10 weeks after infection; its appearance precedes the development of clinical symptoms and an increase in ALT/AST activity. With an adequate immune response, it disappears 4–6 months after infection, approximately during the same period anti-HBs are detected (during the “serological window”, when HBsAg has already disappeared and antibodies to it have not yet appeared, the diagnosis can be confirmed by the detection of anti-HBsAg). HBc IgM). Anti-HBs are also produced during the vaccination process. It should be taken into account that in the fulminant form of acute viral hepatitis B, HBsAg may be absent.

–HBeAg indicates viral replication in hepatocytes; found in serum almost simultaneously with HBsAg, absent in HBV infection caused by a mutant strain of the virus (with a change in the genetic code in the “precore region” and impaired secretion of HBeAg). Anti-HBe (AT to e-Ag) is a serological marker of virus integration; in combination with anti-HBc IgG and anti-HBs indicates the complete completion of the infectious process.

–Anti-HBc (Ab to nuclear Ag) is an important diagnostic marker of infection. Anti-HBc IgM is one of the earliest serum markers of chronic hepatitis B; sensitive marker of HBV infection. Indicates the replication of the virus and the activity of the process in the liver. Its disappearance serves as an indicator of either the sanitization of the body from the pathogen, or the development of the integrative phase of HBV infection. Anti-HBc IgG persists for many years, indicating an existing or previous infection.

–HBV DNA (HBV DNA) and DNA polymerase are diagnostic markers of virus replication.

✧The diagnosis of acute viral hepatitis B is confirmed by detecting HBsAg and anti-HBc IgM in the blood. When the virus is eliminated (recovery), HBsAg should disappear from the blood no later than 6 months after the onset of the disease (in rare cases, it can persist for up to 12 months).

✧When HBV infection becomes chronic (CHB B or carriage of the virus), HBsAg does not disappear from the blood (persists for more than 6 months).

✧HCV: anti-HCV, HCV-RNA.

–HCV RNA is the earliest biochemical marker of infection, occurring within a period of several days to 8 weeks after infection. In cases of recovery from acute viral hepatitis C, viral RNA disappears from the blood within 12 weeks (no later than 20 weeks) after the onset of the first symptoms. The likelihood of spontaneous elimination of the virus if HCV RNA persists beyond the specified time frame is doubtful.

– anti-HCV is determined in the blood no earlier than 8 weeks after infection. Approximately half of patients with clinically manifest acute viral hepatitis C have anti-HCV in their blood at the onset of the disease. In subclinical infection, AT is usually detected much later - on average 41 weeks after the appearance of viral RNA in the blood.

✧HDV: anti-HDV IgM, HDV RNA (HDV replication marker).

ADDITIONAL INVESTIGATION METHODS

■ Stool analysis: decreased content or absence of stercobilin due to cessation of bile flow into the intestines. The appearance of stercobilin in feces during the icteric period of acute viral hepatitis is evidence of resolution of jaundice.

■ Blood concentration of α-fetoprotein (screening for hepatocellular carcinoma).

■ Additional laboratory tests are necessary for differential diagnosis with other chronic liver diseases (markers of autoimmune hepatitis, ceruloplasmin concentration and daily urinary excretion of copper, ferritin concentration, degree of transferrin saturation, etc., see the article “Liver cirrhosis”).

MANDATORY INVESTIGATION METHODS

■ Ultrasound of the liver and spleen: characterized by increased echogenicity of the parenchyma, compaction along the vessels of the liver; with cirrhosis of the liver, splenomegaly is possible.

■ Liver biopsy: although diagnosis can be made without this test, liver biopsy is advisable in most cases of chronic hepatitis to assess the extent of liver damage and plan specific antiviral therapyC.

ADDITIONAL RESEARCH METHODS

■ CT scan of the abdominal cavity: if there are difficulties in establishing a diagnosis or the need for differential diagnosis, for example, with space-occupying processes in the liver.

■ FEGDS: to exclude concomitant pathology of the upper gastrointestinal tract, to identify varicose veins of the esophagus (usually with cirrhosis of the liver).

It is necessary to carry out a differential diagnosis of chronic hepatitis with other chronic liver diseases: alcoholic liver disease, autoimmune hepatitis, hemochromatosis, Wilson-Konovalov disease, etc. The detection of hepatitis virus markers is of greatest diagnostic importance, and in doubtful cases, the results of a liver biopsy. The issues of differential diagnosis of chronic liver diseases are described in detail in the article “Liver Cirrhosis”.

INDICATIONS FOR CONSULTATION WITH OTHER SPECIALISTS

■ Related specialists (nephrologist, hematologist, dermatologist, rheumatologist): with the development of extrahepatic manifestations of chronic hepatitis.

■ Psychiatrist: with the development of severe depression or other mental disorders associated with interferon therapy.

■ Acute viral hepatitis: relief of the main symptoms of the disease and prevention of chronicity of the process and the development of complications.

■ CHV: persistent suppression of viral replication, and, as a result, achieving remission of the disease.

INDICATIONS FOR HOSPITALIZATION

All patients with acute viral hepatitis are hospitalized in an infectious diseases hospital. In the case of a mild course of acute viral hepatitis and compliance with sanitary and anti-epidemic measures, treatment at home is possible (the issue is decided by the attending physician). In case of chronic hepatitis, hospitalization is indicated in case of exacerbation of the disease or the development of complications (bleeding from esophageal varices, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, ascites, etc.).

■ In case of acute viral hepatitis and exacerbations of chronic hepatitis, it is necessary to adhere to bed or semi-bed rest (depending on the severity of the condition).

■ A balanced diet is necessary. The consumption of proteins, sodium and liquid is limited only in case of decompensated cirrhosis of the liver.

■ Vaccination against hepatitis A is advisable. Hepatitis A in patients with chronic liver pathology, including chronic hepatitis, is severe. Vaccination against hepatitis A for chronic hepatitis B is safe and effective.

■ In acute viral hepatitis, treatment is predominantly symptomatic - detoxification infusion therapy, enterosorbents, ursodeoxycholic acid for severe cholestasis, in severe cases - proteolysis inhibitors and glucocorticoids, but their effectiveness is questionable.

■ Specific antiviral therapy is indicated for acute viral hepatitis C. Interferon alpha 5 million IU subcutaneously daily for 4 weeks is usually used, then 5 million IU subcutaneously 3 times a week for 20 weeks, which can significantly reduce the risk of developing CVH C. Alternative option - prescription of peginterferon alfa2a (180 mg/week) or peginterferon alfa2b (1.5 mcg/kg per week for 6 months). Switching to the use of peginterferon alfa2b in combination with ribavirin is indicated if there is no effect from monotherapy with interferon alfa for 3 months (preservation of HCV RNA in the blood). In patients with clinically manifest forms of acute viral hepatitis C, treatment begins when HCV RNA remains in the blood 12 weeks after the onset of the disease (in its absence, repeated three-time studies are required with an interval of 3 months). When diagnosing asymptomatic forms of acute viral hepatitis C, treatment should begin immediately.

CHRONIC VIRAL HEPATITIS B

■ Antiviral therapy for chronic hepatitis B is indicated for patients at high risk of developing progressive liver damage. Interferon alpha and lamivudine are used. Their effectiveness is approximately the same; the choice of a specific drug is carried out on an individual basis (tolerability, availability, etc.). Criteria for the effectiveness of therapy are normalization of the activity of ALT, HBV DNA and HBeAg (with or without the appearance of anti-HBe), reduction of necrotic and inflammatory changes in the liver (according to biopsy).

✧The drug of choice is interferon alphaA. Treatment is carried out for chronic hepatitis B, accompanied by an increase in ALT activity (with an initially normal ALT level, it is possible to induce its increase with glucocorticoids), an HBV DNA titer of 108/l or more, signs of chronic hepatitis according to liver biopsy in the absence of decompensation of liver function.

–Doses of interferon alpha in the treatment of HBeAg-positive patients are 9–10 million IU 3 times a week for 4–6 months. If HBeAg is absent in the blood serum (precore mutant option), the course of treatment should be long - 12 months.

–Persistent disappearance of HBeAg/HBV DNA occurs in 25–40% of patients receiving interferon alfa therapy.

– The most common side effects are flu-like symptoms, myelotoxicity, depression and other mental disorders. If severe side effects develop, it is necessary to reduce the dose (in 10–40% of patients) or discontinue the drug (in 10%). During long-term therapy, the need for prophylactic antidepressants should be considered.

✧Lamivudine is prescribed 100 mg/day orally. In HIV-infected people, the dose is increased to 150 mg/day (other antiretroviral drugs are prescribed at the same time). The duration of treatment is 1 year. If there is no effect, longer courses are permissible, which is also indicated for the HBeAg-negative variant. After 1 year of treatment, persistent disappearance of HBeAg and HBV DNA is observed in 16–18% of cases, histological improvement in 46–56%. After 24 and 36 months, HBeAg seroconversion was observed in 27 and 33%. The probability of the emergence of mutant strains resistant to lamivudine is 14, 38 and 49% after 1, 2 and 3 years of treatment, respectively (clinical signs of exacerbation of hepatitis develop). Lamivudine is usually well tolerated (side effects occur no more often than with placebo). After completing the course of treatment, an exacerbation of the disease is possible, so the patient must be monitored for at least 1 year.

– severe heart disease;

–pregnancy or inability to use effective contraception;

– after organ transplantation (except liver) or red bone marrow;

– decompensated cirrhosis of the liver or hepatocellular carcinoma;

– granulocytopenia less than 1.5 109/l or thrombocytopenia less than 90 109/l;

– active or difficult to treat autoimmune diseases (ulcerative colitis, psoriasis, hyperthyroidism, systemic lupus erythematosus);

CHRONIC VIRAL HEPATITIS C

■ Antiviral therapy for chronic hepatitis C is indicated for patients with high disease activity (HCV RNA is present in the blood serum, increased ALT activity, signs of moderate or severe chronic hepatitis in liver biopsies) and compensated liver functionsA. Child–Pugh class B cirrhosis should be treated by a physician experienced in treating such patients.

✧Combination therapy is usually carried out: peginterferon alfa2b 1.5 mcg/kg subcutaneously once a week or peginterferon alfa2a 180 mcg/kg subcutaneously once a week in combination with ribavirin, the dose of which depends on body weight (less than 65 kg - 800 mg/ day, 65–80 kg - 1000 mg/day, 86–105 kg - 1200 mg/day, more than 105 kg - 1400 mg/day).

–For chronic hepatitis C caused by HCV genotype 1, combination therapy is carried out for 6 months at a low level of viremia, and 12 months at a high level.

–For chronic hepatitis C caused by HCV genotypes 2 or 3, treatment is continued for 6 months (longer courses are necessary only for liver cirrhosis).

–Early virological response (HCV RNA control) is determined after 3 months. If the test remains positive, the further treatment regimen needs to be changed.

–The effectiveness of combination therapy (persistent disappearance of HCV RNA) averages 40–50% (20–30% for HCV genotype 1, 60–70% for HCV genotypes 2 and 3).

✧ Monotherapy with peginterferon alfa2b (1 mcg/kg subcutaneously once a week) or peginterferon alfa2a (180 mcg/kg subcutaneously once a week) is carried out if there are contraindications to taking ribavirin (most often renal failure). The effectiveness of therapy is assessed in the same way as with combination therapy, but after 6 months. If the HCV RNA titer disappears or decreases, treatment is continued for up to 1 year, otherwise therapy is stopped. The effectiveness of monotherapy is 23–25%. Even if elimination of HCV RNA has not been achieved, treatment with interferons slows the progression of the disease and reduces the risk of developing hepatocellular carcinoma.

✧ Side effects are similar to those when using interferon alfa; in addition, hemolysis and dysfunction of the thyroid gland are possible (in 5–10% of cases). If severe side effects develop, reduce the dose of the drugs or discontinue them. Short-term (less than 2 weeks) withdrawal of drugs does not affect the effectiveness of therapy.

■ Antiviral therapy is not justified in patients with low disease activityB (in particular, long-term disease with minimal histological activity and normal ALT levels).

■ Contraindications to treatment with ribavirin.

– presence of severe heart disease;

–end-stage renal failure;

–pregnancy or inability to use effective contraception.

– uncontrolled arterial hypertension;

RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Archive - Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2007 (Order No. 764)

Chronic viral hepatitis, unspecified (B18.9)

General information

Brief description

Chronic viral hepatitis- inflammation of the liver tissue that persists for a long (more than 6 months) period of time.

Protocol code: N-T-026 "Chronic viral hepatitis"
For therapeutic hospitals

ICD-10 code(s):

Chronic viral hepatitis B with delta agent B18.0

Chronic viral hepatitis B without delta agent B18.1

Chronic viral hepatitis C B18.2

Other specified chronic viral hepatitis B18.8
- Other unspecified chronic viral hepatitis B18.9

Classification

Classification of chronic viral hepatitis

1. According to etiological criteria:

Chronic viral hepatitis B (CHBV): HbeAg-positive and HBeAg-negative (with pre-cor zone mutation); HbsAg-negative (with a mutation in the S gene);

Chronic viral hepatitis C (CHC): 1b / 1a / 2 / 3 / 4 genotype; with high or low viral load;

Chronic viral hepatitis D (CVD): co- and superinfection (CVD or CHB with delta agent);

Chronic viral hepatitis, not otherwise classified.

2. According to the phase of virus replication:

Replicative;

Low (non)replicative;

Immune tolerance (for viral hepatitis B).

3. By degree of activity*:

Minimum;

Weakly expressed;

Moderately expressed;

Expressed.

4. By stage:

No fibrosis;

Mild (portal) fibrosis;

Moderate (periportal) fibrosis;

Severe (septal, bridging) fibrosis;

Cirrhosis.

*The degree of activity of chronic hepatitis is determined by the severity of parenchymal necrosis and inflammatory cell infiltration using a semi-quantitative (rank) analysis, assessing the severity of histological signs in points (Knodell index, METAVIR scale).

Activity level	Histological index activities**	ALT activity (approximate estimate)
I - minimum	1-3 points	Norm
II - weakly expressed	4-8 points	Increase to 3 standards
III - moderate	9-12 points	Increase from 3 to 10 norms
IV - pronounced (severe)	13-18 points	Increase over 10 norms

**Evaluation of histological activity index

Risk factors and groups

The risk group includes:
- drug addicts;
- persons with promiscuous sexual relations;
- patients of hemodialysis departments;
- patients requiring repeated transfusions of blood or its components;
- medical workers;
- family members of the virus carrier.

The most significant routes of infection through which massive transmission of the pathogen occurs are transfusion of blood and its products (70% of cases of post-transfusion hepatitis), injections and other invasive interventions, hemodialysis, organ transplantation, tattooing. The role of sexual, vertical and perinatal routes of infection is more significant for CHBV. In 40% of cases, it is not possible to establish the route of transmission of the pathogen. The main route of transmission of HCV is parenteral: transfusions, organ transplants from infected donors, intravenous drug administration.

Diagnostics

Diagnostic criteria

Complaints and anamnesis
CHB often occurs with symptoms of asthenovegetative syndrome; patients are concerned about weakness, fatigue, insomnia or flu-like syndrome, muscle and joint pain, and nausea. Less typical are pain in the epigastric region, diarrhea, skin rash, and jaundice.

In most patients with CHC, even against the background of high levels of serum transaminases, the disease is often asymptomatic or with symptoms of asthenovegetative syndrome. Less commonly observed are nausea, loss of appetite, itching, arthralgia and myalgia.

CHVD is the outcome of superinfection with the hepatitis D virus in patients with CHBV and has, in comparison with CHBV and CHVHC, more pronounced clinical manifestations.

Physical examination

On physical examination, the main objective symptom is hepatomegaly, increased liver density. With high activity of the process, as well as the formation of liver cirrhosis, splenomegaly is possible, sometimes lymphadenopathy, the presence of liver signs (palmar and plantar erythema, spider veins, hyperpigmentation).

Instrumental examination

Liver biopsy (assessment of hepatitis activity and stage);

Endoscopic examination, contrast study of the esophagus with barium (esophageal varices);

Ultrasound examination of the hepatobiliary system (hepatomegaly, splenomegaly, changes in the structure of the liver);

Doppler examination of hepatic and portal blood flow;

Computed tomography or magnetic resonance imaging for a more accurate assessment.

4. Indications for consultation with specialists

Formation and progression of portal hypertension: spontaneous bacterial peritonitis, portosystemic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, secondary hypersplenism with cytopenia (bone marrow aplasia), coagulopathy (consumption), DIC syndrome.

List of main diagnostic measures:

General blood test;
- general urine analysis;
- coprogram;
- liver biochemical tests (ALT, AST, alkaline phosphatase, GGTP or GGT, bilirubin, serum proteins, coagulogram or prothrombin time, creatinine or urea);
- serological markers (HBsAg, HBeAg, anti-HBc, HBe IgG, anti-HBc IgM, anti-HBe IgG, DNA HBV, anti-HCV total, RNA HCV, anti-HDV, RNA HDV);

Ultrasound examination of the hepatobiliary system;

Endoscopic examination of the esophagus and stomach.

List of additional diagnostic measures:

Doppler study of hepatic and portal blood flow;

Computed tomography - for a more accurate assessment of the structure of the liver;

Magnetic resonance imaging;

Liver biopsy;

Barium examination of the esophagus.

Laboratory diagnostics

Changes in general blood count are uncommon and are more often observed as side effects of antiviral therapy.
Biochemical changes in the blood include:
- cytolysis syndrome (increased activity of ALT, AST, aldolase, LDH, 4,5-ornithinecarbamyltransferase);
- cholestasis syndrome (increased activity/content of alkaline phosphatase, 5-nucleotidase, GGTP, bilirubin (direct fraction), bile acids, cholesterol, b-LP, phospholipids);
- hepatocellular failure syndrome (decreased levels of albumin, cholinesterase, prothrombin, proconvertin, delayed release of bromsulfalein);
- immune inflammation syndrome (increased content of g-globulins, IgA, IgM, IgG, increased thymol test, decreased sublimate test, the presence of autoantibodies: antinuclear (ANA), anti-smooth muscle (ASMA), to liver and kidney microsomes type 1 (LKM-1) , to soluble liver antigen (SLA));
- shunt syndrome (increased levels of ammonia, phenols, free amino acids).

Viruses are identified based on serological markers:

HBsAg, HBeAg, anti-HBc, HBe IgG, anti-HBc IgM, anti-HBe IgG, DNA HBV;

Anti-HCV total, HCV RNA;

Anti-HDV, HDV RNA.

Differential diagnosis

2. Storage diseases: fatty hepatosis, hemochromatosis, hepatolenticular degeneration, amyloidosis.

3. Diseases of the cardiovascular system: constrictive pericarditis, circulatory failure of II and III degrees (“congestive liver”).

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Treatment

Treatment goals:

Prevention of disease progression;

Virus eradication;

Improvement of the histological picture of the liver;

Reducing the risk of liver cirrhosis and liver failure;

Reducing the risk of hepatocellular carcinoma;

Improving the patient's quality of life.

Non-drug treatment

Gentle mode (avoid physical overload, overheating, hypothermia);
- diet No. 5;
- mandatory exclusion of any alcohol-containing drinks.

Drug treatment

In the treatment of chronic viral hepatitis, antiviral therapy using interferons and nucleoside/nucleotide analogues plays a leading role. The activity of the process, clinical, biochemical and histological changes in the liver are taken into account.

Indications for antiviral therapy are:

Progressive and chronic course;

Availability of replication markers;

Increase in ALT level by more than 2 times (for CHBV);

Histological signs of activity.

Contraindications for the use of interferons are:

Autoimmune diseases;

Depressive states;

Coronary heart disease;

Vascular diseases of the brain;

Kidney failure;

Diabetes mellitus;

Pregnancy;

Anemia or inability to tolerate anemia.

Predictors of the effectiveness of antiviral therapy are:

Short duration of illness;

Young age (up to 45 years);

Female gender;

No liver cirrhosis;

Absence of mixed hepatitis;

A distinct increase in ALT at the beginning of treatment;

Lack of excess body weight;

No history of IFN therapy.

Predictors of failure of antiviral therapy are:

Virus factors:

Genotype 1.4 for HCV, HBV mutant strain;

Features of the disease:

Severe fibrosis and cirrhosis;

Mixed cryoglobulinemia;

Mixed hepatitis, HIV coinfection;

Long duration of the disease (over 10 years);
- relapse.

Patient factors:

Old age - over 65 years old;

Alcohol abuse;

Male gender;

African race;

Obesity.

For the treatment of CHB, pegylated interferons are used in monotherapy and nucleotide/nucleoside analogues.

The standard dose of pegylated interferon α2a is 180 mcg once a week, pegylated interferon α2b is 1.5 mcg/kg once a week. The standard duration of therapy is 24 weeks, but it is currently being revised upward to 48 and even 96 weeks.

As an alternative, and if there are contraindications to interferon therapy, nucleotide/nucleoside analogs are used (lamivudine 100 mg/day or adefovir 10 mg/day or entecavir 0.5 mg/day). Treatment in HBe-positive patients lasts until seroconversion (appearance of anti-HBe) and disappearance of HBV DNA is achieved, in HBe-negative patients - until HBV DNA disappears for at least 24 weeks. In the absence of seroconversion and negative qualitative PCR, the effectiveness of therapy is assessed by reducing the viral load (no more than 104), and the duration of therapy in these cases can be indefinitely long.

During treatment with nucleotide/nucleoside analogues, resistance may occur (usually to lamivudine) in the form of worsening of the disease, an increase in ALT, and an increase in viral load. In these cases, further treatment with lamivudine is combined with adefovir.

For chronic hepatitis C, combined antiviral therapy with interferons and ribavirin is used. The duration of treatment for genotypes 1,4,5 and 6 is 48 weeks, and for genotypes 2 and 3 - 24 weeks. The standard dose of pegylated interferon α2a is 180 mcg once a week, pegylated interferon α2b is 1.5 mcg/kg once a week. The dose of ribavirin in the treatment of patients with genotypes 1,4,5 and 6 is 1200 mg per day, with genotypes 2 and 3 - 1000 mg per day.

For chronic hepatitis D, standard doses of pegylated interferons are used. The recommended duration of treatment is from 48 to 96 weeks.

In cases of concomitant cholestasis in patients with chronic viral hepatitis, the effectiveness of ursodeoxycholic acid (500-1000 mg/day) has been proven. If serious side effects of therapy that cannot be corrected occur (leukopenia less than 1.8, thrombocytopenia less than 80, severe anemia, major depression, autoimmune diseases), discontinuation of therapy is considered. In patients with chronic hepatitis C, therapy is also discontinued in the absence of a virological response after 12 weeks of treatment.

Further management, principles of medical examination

Clinical examination is carried out by a polyclinic therapist, gastroenterologist, and infectious disease specialist. Examinations to determine biochemical indicators of inflammatory activity, markers of viral replication and other tests are carried out at least once every six months, and when conducting AVT - once a month.
6 months after the end of treatment, the levels of ALT, HCV RNA and HBV DNA are examined. If the ALT level is normal, HCV RNA and HBV DNA are negative, then the effect is regarded as persistently positive.

The liver is the main (although not the only) organ in which the metabolism of drugs and other xenobiotics is carried out (you can read about drugs that affect the liver here).
  There are 3 main types of interactions and mutual influences between drugs and the liver:
  1) metabolic transformations (biotransformation) of drugs in the liver;
  2) the effect of liver diseases on drug metabolism;
  3) the damaging effect of drugs on the liver.
  This must be taken into account in clinical psychiatry and narcology due to the widespread use, often in medium and high doses, of psychotropic and other drugs that have hepatotoxic properties or (more often) create a high metabolic load on hepatocytes.
  Often, it is not the drug that has hepatotoxic properties, but its metabolite, which is formed during the biotransformation of the drug in the liver. A common example of this is paracetamol (acetaminophen). The formation of toxic derivatives is typical for drugs metabolized with the participation of cytochrome P450 family. It is characteristic that the toxic effects of drug metabolites may accompany their pharmacological activity.
  Drug metabolism usually consists of two stages: non-synthetic (1) and synthetic (2) reactions.
  In the first (initial) stage, non-synthetic reactions occur, including oxidation, reduction, hydrolysis, or a combination of these processes. The resulting drug metabolites may have pharmacological activity, sometimes higher than that of the parent substance.
  At the second (final) stage of metabolism, synthetic reactions occur, during which the intermediate metabolite combines with an endogenous substrate and forms a highly polar product, excreted in urine or bile (polarity is a property that determines the ability of a substance to be excreted). The main synthetic reactions are conjugation with glucuronic acid, conjugation with amino acids (glutamine and glycine), acetylation, sulfation and methylation. The products of synthetic reactions usually (but not always) do not exhibit pharmacological activity.
  Oxidation reactions occur with the participation of a complex complex of microsomal enzymes, the basis of which is the hemoprotein cytochrome P450.
  There is a limit to the rate of metabolism of drugs and psychoactive substances. The kinetic properties of enzymes involved in the metabolism of xenobiotics are such that the rate of the reactions they catalyze cannot exceed a certain value. At therapeutic doses of drugs (or low doses of surfactants), only a small part of the active centers of the enzyme is occupied in the reaction. As the plasma concentration of the metabolized substance increases, the active centers of the enzyme are almost completely occupied in the reaction. The intensity of biotransformation stops increasing in proportion to the concentration of the substance and reaches a threshold saturation value. Similar patterns are observed in the metabolism of some anticonvulsants and ethanol.

Liver diseases in the twenty-first century are hardly less common than lesions of the cardiovascular system, which have firmly established themselves as the most common pathologies in the human population. This is facilitated by the growth of harmful emissions from industrial facilities, violation of safety regulations when working with aggressive chemicals, and the use of numerous medications. In the International Classification of Diseases (ICD-10), hepatitis is characterized as a viral pathology. Indeed, the bulk of cases are a consequence of infection, but there are other factors that cause chronic damage to the liver tissue:

1. Poisoning by household and industrial poisons.
2. Incorrect or forced massive use of pharmacological agents that have a toxic effect.
3. The emergence of aggression of the immune system against hepatocyte cells.
4. Circulatory disorders.

Chronic hepatitis (ICD-10 code - B18) is an inflammatory disease of the liver that lasts more than six months.

In short, pathogenesis, that is, the formation mechanism, is based on irreversible cell death under the influence of damaging factors. The proportion of functioning organ tissue decreases, which increases the load on the remaining hepatocytes. The development of the disease may be preceded by an acute form, which cannot be cured due to severe immunodeficiency or high activity of the etiological factor (for example, a virus). An asymptomatic course is also possible - the unfavorable process does not manifest itself in any way, but lasts for months and years until the regenerative properties of the liver are exhausted.

Classification of chronic hepatitis

All pathologies known to specialists are divided into several options, a description of which can be presented in the table:

Type of hepatitis	Circumstances of development	Peculiarities
Infectious	The causative agents are viruses of types B, C, D. The route of infection is parenteral (penetration into the bloodstream), vertical (intrauterine transmission from a pregnant woman to the fetus), lactation (through breast milk when feeding a child), sexual (through unprotected sexual contact). A person can become infected when using medical instruments during invasive procedures (accompanied by a violation of tissue integrity) if there are remains of blood from a hepatitis patient on the surface. The list of such interventions includes injections - the risk is posed by repeated injections with disposable syringe needles. Manicure accessories that are not properly sterilized and razors that cause cuts are dangerous. Hepatitis B is called transfusion-related because infection often occurs during a blood transfusion.	It does not always manifest itself immediately; it often has a latent (hidden) course, in which the disease is detected only when a complication appears: cirrhosis, functional liver failure.
Toxic	Its immediate cause is the destructive effect of various types of poisons on liver cells. Includes chronic alcohol damage as well as drug-induced inflammation (drug-induced hepatitis). It often develops during prolonged contact with substances such as ethylene glycol, white phosphorus, and carbon tetrachloride.	Most often associated with unfavorable production factors, especially if a person works without proper protective equipment. Pharmacological agents are also of great importance: antipyretics (Paracetamol), antituberculosis drugs (Isoniazid, Rifampicin), sulfonamides (Biseptol), antiarrhythmic drugs (Amiodarone), cytostatics (Methotrexate), antibiotics (Tetracycline), etc.
Autoimmune	It is characterized by inflammatory-necrotic changes. Damage to hepatocytes is carried out by antibodies - they are produced by the person’s own immune system. The exact reason why it perceives liver tissue as foreign has not yet been identified.	It can be combined with other autoimmune diseases and syndromes, most often affecting young people.
Ischemic	Lack of oxygen (hypoxia) due to disturbances in the blood supply system leads to a malfunction of the nutritional mechanism of hepatocytes. Metabolic processes are distorted, ballast substances accumulate in the cells - dystrophy develops.	The most common type is fatty liver degeneration (steatohepatitis) - a condition that precedes cirrhosis and, in contrast, is reversible.
Cryptogenic	It is a process of destruction (destruction) of liver tissue, in which viral and toxic effects, as well as immune aggression, are excluded. The triggering factor for inflammation cannot be identified. According to ICD-10, this type is encrypted separately under code B19.	Chronic cryptogenic hepatitis requires careful differential diagnosis and is confirmed only if there is precise confidence in the absence of infectious or other etiological markers.

Chronic active hepatitis can manifest itself in primary biliary cirrhosis and sclerosing cholangitis, copper metabolism disorders, and alpha-1-antitrypsin deficiency (a protein that reduces the activity of certain enzymes and thereby performs a protective function in the body). It also develops as a secondary process in diseases of the gastrointestinal tract and severe systemic infections.

Symptoms

In cases of disorders affecting the tissue (parenchyma) of the liver, a rather multifaceted clinical picture is observed. At the same time, the patient’s complaints do not always appear immediately after the start of the pathological process, which can proceed hidden for a long time and manifest itself with clear signs only with the development of serious disorders of organ function.

Classic manifestations

These include symptoms of chronic hepatitis such as:

1. Headache, drowsiness during the day and insomnia at night, irritability followed by apathy, lethargy, depressed mood, decreased tolerance to physical activity.
2. Dyspeptic syndrome (lack of appetite, nausea, vomiting, weight loss).
3. Jaundice coloration of the skin and mucous membranes, itching of varying intensity.
4. Hepatosplenomegaly (enlargement of the liver and spleen, expansion of their boundaries, revealed during examination, complaints of heaviness in the abdomen).
5. Dull, aching pain in the right hypochondrium and epigastrium, constant or periodic, pulling - in the joints and muscles.
6. Fever (more pronounced during exacerbations, this is explained by activation of the inflammatory process).
7. Increased bleeding of the gums and nasal mucosa.

All of these symptoms are observed for a long time; with immunodeficiency, massive intake of medications, or contact with poisons, the patient’s condition worsens.

The clinical picture of chronic hepatitis C is often accompanied by depressive disorders.

It is necessary to pay attention to this sign during diagnosis, since latent forms are characteristic of this variant of viral liver damage.

Additional manifestations

The second group of signs characterizing chronic hepatitis affects the skin, manifesting itself as a rash. It can be classified as follows:

• recurrent urticaria;
• erythema nodosum;
• pyoderma gangrenosum;
• petechiae.

If classic symptoms are absent or erased, the patient may think about allergies, which slows down the diagnostic search and leads to erroneous interpretation of objective disorders.

Among the additional manifestations, one can also name mixed cryoglobulinemia, observed in hepatitis C. It is an inflammation of small-caliber vessels due to the deposition of serum proteins in their walls and often causes arthritis, nephritis - damage to the joints and kidneys, respectively.

In children, chronic viral hepatitis type B or C predominate. They are characterized by the same symptoms as in adults. However, the transition of acute forms to constantly persistent (existing) variants in a child occurs much more often due to an imperfect immune response.

Diagnostics

It begins with a survey and examination in the doctor’s office - at the initial consultation, the dominant complaints and clinical signs are clarified, and a plan for further action is drawn up. Many cities are introducing the practice of free anonymous surveys. Despite the estimated high cost of testing, establishing a diagnosis in the early stages of the disease significantly increases the chances of a successful treatment outcome, and therefore reduces the percentage of people who are unable to work due to liver damage.

These include blood tests such as:

1. General (detects the presence of signs of inflammation, anemia).
2. Biochemical (makes it possible to differentiate liver damage from other diseases and assess the likely prognosis).
3. Enzyme immunosorbent (carried out to detect antibodies to hepatitis viruses).

Chronic liver diseases are manifested by a number of laboratory syndromes:

• Cytolysis (destruction of hepatocytes).

  It is characterized by a sharp increase (several times) in the level of liver enzymes: ALT, AST, LDH.

• Mesenchymal inflammation.

  The functional basis is the development of cirrhosis (replacement of parenchyma with connective tissue in the form of fibrous nodes). A biochemical blood test shows an increase in C-reactive protein (CRP), seromucoid, and gamma globulin fraction.

• Cholestasis.

  The main marker is an increase in the level of alkaline phosphatase. The indicators of bilirubin and its fractions also increase.

With cytolysis, there is a massive release of enzymes that were previously contained in hepatocytes; with cholestasis, there is an accumulation of bile due to a violation of its outflow into the intestine. Any change that is pathological in nature affects the patient’s health status and can be detected through tests.

Instrumental diagnostics

Includes test options such as:

Ultrasound is considered the most convenient and safe, but a comprehensive examination is required to establish a final diagnosis. The doctor evaluates the results of not only instrumental and laboratory tests, but also the clinical signs detected during the examination, and then decides on further tactics.

Treatment of chronic hepatitis

To help the patient, a plan of therapeutic measures is drawn up - the choice of specific options depends on what type of inflammatory process is identified during diagnosis. Not only pharmacological drugs are used, but also non-drug methods.

Elimination (breaking contact with the provocateur), diet correction

Treatment of chronic hepatitis caused by toxins, first of all, requires stopping their entry into the body. The patient is hospitalized in a hospital or observed on an outpatient basis (at home with regular visits to the doctor at the clinic), after which he is subject to transfer to work with less harmful working conditions. It is possible to alleviate the condition of a drug-induced injury only by stopping the drug, which has become a poison for the liver. If a patient has an alcohol addiction, an anonymous survey, consultation with a narcologist, or a psychotherapist are necessary - methods that convince people to give up alcohol.

A diet for chronic hepatitis should correspond to the characteristics of a complete diet in terms of calorie content and include vegetables, fruits, lean meats and fish. Alcohol, fatty, fried foods, flavor enhancers and synthetic food additives, seasonings and spices are strictly prohibited.

Drug therapy

Determined by the variant of the disease. The etiology of chronic hepatitis B, C, D implies a viral infection, therefore the following is required:

• interferons;
• protease inhibitors.

These drugs are able to suppress the replication (multiplication process) of viral agents and thereby reduce their concentration. The most commonly prescribed drugs are Telaprivir, Viferon, Sofosbuvir. They must be used in long courses.

Treatment of chronic hepatitis with autoimmune aggression is impossible without such remedies as:

They are necessary to reduce the active production of antibodies and reduce their damaging effect on liver cells; they belong to the group of immunosuppressants.

As for ischemic hepatitis, the following groups of medications are used:

• B vitamins;
• antioxidants (Tocopherol acetate);
• hepatoprotectors (Gepabene, Silymarin).

Impaired blood flow occurs due to narrowing of the lumen of the vessels of the portal vein system, so surgical intervention may be necessary.

Symptoms of chronic hepatitis are difficult for the patient to tolerate, and therapy should be accompanied by regular clinical and laboratory monitoring; with the viral and autoimmune variants, it continues for several years.

Prognosis and prevention

Hepatitis is usually detected in the later stages, when the asymptomatic period of formation of changes has already passed. This creates a tendency to develop cirrhosis and carries a risk of liver failure. The prognosis is unfavorable, but there are some nuances:

1. Establishing a diagnosis before the formation of connective tissue in the parenchyma with timely initiation of therapy provides a chance to stop or significantly slow down the process.
2. In case of toxic damage, interruption of contact with a toxic substance leads to a clear regression of symptoms - if the patient is in the pre-cirrhotic stage, many changes are reversible.
3. For the treatment of hepatitis C, drugs have been developed that can stop the pathological process - these are Sofosbuvir and its analogues. They show excellent efficiency even at a late stage of the flow.

Early detection of viral infection allows one to expect a good prognosis if the patient receives adequate therapy and does not yet have pronounced liver failure. In the autoimmune form, the patient’s chances of improving their condition depend on the type of pathology: with the first type the course is more favorable, with the second it is considered aggressive.

Primary and secondary prevention of chronic hepatitis consists of using only disposable instruments, individual razors, and manicure sets. If this is not possible, quality controlled sterilization must be carried out. Protective equipment for medical staff - gloves, masks, goggles.

Blood donors are allowed to participate in the procedure only if there are no parenteral infections, but the donated material must be re-tested before transfusion to the recipient. Diagnosis of chronic viral hepatitis is complicated by the fact that antibodies do not appear in the blood immediately, so extreme vigilance is necessary.

The main role in the development and activation of the epidemiological process is played by a person infected with the HAV virus. The subclinical, anicteric variant of the disease is especially dangerous, when the infection goes through the incubation stage and releases a virus that is excreted in feces. The process of releasing the hepatitis A pathogen into the external environment continues until the initial clinical manifestations of the disease and lasts up to four weeks. The first two weeks from the onset of the disease are considered the most dangerous in terms of contagiousness. During this period, the virus can be detected not only in feces, but also in urine, semen, vaginal discharge and menstrual blood.

Causes of hepatitis A

Pathogenesis

Hepatitis A is considered one of the most common infectious diseases in the world. Until the end of the 19th century, the disease was called catarrhal jaundice and was associated with an inflammatory process in the bile ducts. The infectious etiology of hepatitis A was identified by the great clinician S.P. Botkin, since then this concept has been leading in the practice of diagnosing and treating hepatitis, and it was possible to specify and identify the causative agent only in 1973. The HAV (hepatitis A) virus belongs to the group of small picornaviruses, lacking a lipoprotein layer, with a single-stranded RNA structure. The pathogen is very resistant to various factors and is able to survive in the environment for several months at a comfortable room temperature. Even when frozen, the virus does not lose viability for 1.5-2 years, and its acid-resistant shell helps to overcome the protective secretions of the stomach and penetrate the liver. A person who has recovered from hepatitis A retains stable immunity to the virus for life.

The infection can also be inactivated by boiling or steaming. the use of disinfectants - chloramine, formalin, as well as ultraviolet irradiation makes it possible to neutralize the hepatitis A virus.

Symptoms of hepatitis A

Treatment of hepatitis A

The therapeutic strategy for hepatitis A is most often limited to a special gentle diet, which involves limiting fats and adding carbohydrates. As a rule, this is the purpose of diet No. 5 according to Pevzner. Bed rest, reduced physical activity and stress, and drinking plenty of fluids are also helpful. To relieve symptoms, treatment of hepatitis A involves the use of choleretic drugs, infusions, hepatoprotectors, and antispasmodics. The strategy and tactics of HAV therapy can be systematized and presented as follows:

Basic activities	Bed rest
	Diet, specific therapeutic nutrition (table No. 5). In the acute period of the disease and in moderate forms of hepatitis, diet No. 5a is indicated
Detoxification measures to cleanse the gastrointestinal tract and liver	Purpose of enterosorbents – polyphepan, enterosgel, lignosorb
Detoxification measures to cleanse the blood through the urinary system, kidneys	Drink plenty of alkaline water (mineral water, freshly squeezed vegetable and non-acidic fruit juices) It is possible to use drugs - diuretics, as well as glucocorticosteroids
Detoxification measures to remove toxins through the skin	Warmth, regular baths, showers, skin care to activate sweating and blood microcirculation
Neutralization of organ tissue hypoxia, lipid peroxidation	Purpose of antioxidants - vitamins E, A, C, PP, Essenitale, Riboxin
In severe cases of the disease, extracorporeal detox methods are indicated	Plasmapheresis, plasmasorption, hemosorption, hemoxygenation
Measures to help correct liver protein functions and its regeneration	Amino acids, albumin, intravenous plasma Vitamin and mineral therapy (oral, injection) Preparations containing potassium
Neutralization of necrosis and fibrosis of liver tissue	Prescription of proteinase inhibitors - gordox, contrical, hormonal drugs
Relief of choleostasis	Purpose of ursodeoxycholic acid and other types of acids of this group, preparations containing it - ursofalk, henofalk, taurofalk Application of enterosorbents Tubage or prescription of choleretic drugs
Treatment of hepatitis A to correct hemostasis	Prescriptions in accordance with coagulogram information
Correction of functions of the gastrointestinal tract and biliary system	Prescription of probiotics, prebiotics, enzymes

Prevention

Preventive measures against many viral diseases include maintaining personal hygiene. If the nose and mouth are vulnerable to the influenza virus in terms of infection, through which the pathogen can enter the body, then the prevention of hepatitis A means cleanly washed hands, because it is no coincidence that HAV was called “the disease of dirty hands.” Just as in cases of other intestinal diseases, preventive measures consist of processing food, purifying or boiling water and following the simplest rules of sanitary and hygienic standards. In this sense, not only personal preventive efforts are effective, but also systematic testing, treatment of drinking water, and assessment of the purity and safety of food products by sanitary and epidemiological services at the level of state programs.

In addition, prevention of hepatitis A is medical examination of the population and monitoring of persons who are in contact with patients infected with the HAV virus. Monitoring of the condition of contact persons is carried out for 30-35 days with mandatory weekly recording of clinical symptoms, checking the activity of ALT (biochemical blood test), and identifying antibodies to the virus (immunoenzyme test). If contact persons are pregnant women and children under 12-14 years of age, administration of a prophylactic dose of immunoglobulin is indicated. Timely vaccination against hepatitis A is considered the most effective method of prevention throughout the world, especially in areas with high epidemiological levels of infection.

• Wash your hands thoroughly, preferably with soap, after each visit to a private or public toilet.
• Wash raw vegetables and fruits thoroughly, preferably with boiled water, or in extreme cases, running water for a long time.
• If possible, it is advisable to pour boiling water over vegetables and fruits, especially if they are intended for children.
• Drink raw water only from clean sources tested by the relevant services. If the water source is in doubt, the water should be boiled for 3-5 minutes.
• Wash your hands every time before preparing food, as well as before eating.
• Wash your hands after visiting public places, after traveling in transport.
• Teach children to observe the rules of personal hygiene.
• Do not try fruits and berries at spontaneous markets.
• Do not eat foods of questionable appearance.
• Regularly check hygiene certificates and shelf life of products purchased in stores and supermarkets.
• Do not use cutlery or personal hygiene items for people infected with hepatitis.

Vaccination against hepatitis A

Today, vaccination against hepatitis A is considered the basis of preventive measures to help stop the population from becoming infected with the HAV virus. A vaccine is a neutralized virus that is highly immunogenic. Vaccination is carried out twice with an interval of six months and a year. Immune antibodies to the administered vaccine appear in the body after 1.5-2 weeks, immune protection after vaccination lasts for at least six years, maximum ten years.

Vaccination against hepatitis A is believed to be effective from a very early age, however, it is most often given from the age of three. Vaccinations are also indicated for adults who have not had HAV and those included in groups of potential infection (risk groups).

• Medical personnel of inpatient medical institutions having contact with groups of patients, as well as personnel of infectious diseases hospitals.
• All employees of children's schools and preschool institutions, without exception.
• Employees working in public catering establishments, as well as persons working in the water supply system of populated areas.
• People with a history of liver disease.
• People who plan to travel to countries with high epidemiological levels of hepatitis infection.
• Persons in contact with patients/carriers of hepatitis A (family members, relatives).
• Persons who have sexual contact with infected partners.