Acute viral hepatitis. Epidemiology of hepatitis C. Symptoms of hepatitis C

Hepatitis C (viral hepatitis C, HCV, Hepatitis C) is an anthroponotic infectious disease with a contact mechanism of pathogen transmission, characterized by a mild or subclinical course of the acute period of the disease, the frequent formation of chronic hepatitis C, the possible development of liver cirrhosis and hepatocellular carcinoma.

ICD-10 codes
Q17.1. Acute hepatitis C.
Q18.2. Chronic hepatitis C.

Hepatitis C virus

The causative agent is hepatitis C virus (HCV) and belongs to the Flaviviridae family. The virus has a lipid envelope, spherical shape, the average diameter is 50 nm, the nucleocapsid contains a single-stranded linear RNA. The genome contains about 9600 nucleotides. Two regions are distinguished in the HCV genome, one of which (locus core, E1 and E2 / NS1) encodes the structural proteins that make up the virion (nucleocapsid, envelope proteins), the other (locus NS2, NS3, NS4A, NS4B, NS5A and NS5B) - non-structural (functional) proteins that are not part of the virion, but have enzymatic activity and are vital for virus replication (protease, helicase, RNA-dependent RNA polymerase). The study of the functional role of proteins encoded in the nonstructural region of the HCV genome and involved in virus replication is of exceptional importance for the creation of new drugs that could block viral replication.

It has been established that HCV circulates in the human body as a mixture of mutant strains that are genetically different from each other and are called "quasi-species". A structural feature of the HCV genome is its high mutational variability, the ability to constantly change its antigenic structure, which allows the virus to avoid immune elimination and persist for a long time in the human body. According to the most common classification, there are six genotypes and over a hundred subtypes of HCV. In different regions of the Earth, different genotypes of the virus circulate. So, in Russia, genotypes 1c and 3a are predominantly common. The genotype does not influence the outcome of the infection, but it predicts the effectiveness of treatment and in many cases determines its duration. Patients infected with genotypes 1 and 4 respond worse to antiviral therapy. Only chimpanzees can serve as an experimental model for studying HCV.

Epidemiology of hepatitis C

Viral hepatitis C - anthroponosis;

the only source (reservoir) of the infectious agent- a person with acute or chronic hepatitis. Viral hepatitis C is classified as an infection with a contact (blood contact) mechanism of transmission of the pathogen, the implementation of which occurs naturally (vertical - when the virus is transmitted from mother to child, contact - when using household items and during sexual contact) and artificial (artificial) ways.

Artificial route of infection can be implemented through blood transfusions of infected blood or its preparations and any parenteral manipulations (medical and non-medical) accompanied by a violation of the integrity of the skin and mucous membranes, if the manipulations were carried out with instruments contaminated with blood containing HCV.

Natural routes of infection with hepatitis C are less common than in hepatitis B, which is probably associated with a lower concentration of HCV in biological substrates. The risk of infection of a child by a seropositive mother averages 2%, increases to 7% if HCV RNA is detected in the blood of a pregnant woman, up to 10% if a woman practices intravenous drug use, and up to 20% if a pregnant woman is diagnosed with co-infection with HCV and HIV. Breastfeeding is not contraindicated for infected mothers, but if there are cracked nipples, according to some researchers, breastfeeding should be avoided. The infection is rarely transmitted from child to child, so the child's attendance at school and his communication with other children, including contact sports, are not limited. There is no need to limit household contacts, except for those that may lead to contact with infected blood (sharing a toothbrush, razor, manicure accessories, etc.).

Infection of regular sexual partners-carriers of HCV rarely occurs sexually. Therefore, when recommending HCV carriers to inform their sexual partners about the infection, it should be emphasized that the risk of transmission through sexual contact is so small that some experts consider the use of condoms optional. With a large number of sexual partners, the likelihood of infection increases.

A particular danger in the spread of HCV is the intravenous administration of narcotic drugs without following the rules of safe injection practice. The majority of newly registered patients with ACS (70–85%) have indications for the intravenous use of narcotic drugs. The rise in the incidence of hepatitis C in Russia in the 90s is due to the growth of drug addiction. According to experts, in Russia there are more than 3 million people who use narcotic and psychotropic substances, among them in recent years the number of anti-HCV positive has increased by 3-4 times, so this category of people is especially dangerous as a source of hepatitis C virus. Risk group patients undergoing hemodialysis, patients with oncological and hematological pathology and others receiving long-term and repeated inpatient treatment, as well as medical workers who have contact with blood, and donors also speak. It is also possible to become infected with HCV during transfusion of infected blood products, although in recent years, due to the mandatory determination of anti-HCV in donors, the number of persons infected after blood transfusions has sharply decreased and amounts to 1–2% of all cases of infection. However, even the use of a highly sensitive ELISA method for testing donor blood does not completely eliminate the possibility of transmission of this infection, therefore, in recent years, the blood product quarantine method has been introduced into the transfusion service. In some countries of the world, donated blood is tested for the presence of HCV RNA by PCR. The pathogen can be transmitted not only during parenteral medical procedures (injections, dental and gynecological procedures, gastro-, colonoscopy, etc.), but also when tattooing, ritual incisions, piercing, manicure, pedicure, etc. when using instruments contaminated with infected blood.

The natural susceptibility of humans to HCV is high. The probability of infection is largely determined by the infectious dose. Antibodies detected in the body of an infected person do not have protective properties, and their detection does not indicate the formation of immunity (the possibility of re-infection with HCV with both a different and a homologous strain has been shown).

HCV in the world is infected with about 3% of the population (170 million people), approximately 80% of people who have had an acute form of the disease develop chronic hepatitis. Chronic HCV infection is one of the main causes of liver cirrhosis and the most common indication for orthotopic liver transplantation.

An analysis of the incidence of acute hepatitis C in our country shows that in 2000, compared with 1994 (the first year of official registration), the incidence increased by almost 7 times: from 3.2 to 20.7 per 100,000 population. Since 2001, the incidence of acute hepatitis C has been declining, and in 2006 the rate was 4.5 per 100,000 population. It should be borne in mind that the official registration data are probably not complete, since it is impossible to take into account those cases of acute viral hepatitis that occur without jaundice (with acute hepatitis C, the proportion of such patients is about 80%). The main group of cases are people aged 20–29 years and adolescents. In Russia, the sharp rise in the incidence of acute viral hepatitis observed in 1996–1999 was replaced by an epidemic of chronic viral hepatitis. In the structure of chronic liver lesions, the proportion of viral hepatitis C reaches more than 40%.

The pathogenesis of hepatitis C

The pathogenesis of hepatitis C is not well understood.

After infection, HCV enters hematogenously into hepatocytes, where it predominantly replicates. Damage to liver cells is due to the direct cytopathic effect of virus components or virus-specific products on cell membranes and structures of the hepatocyte and immunologically mediated (including autoimmune) damage directed to intracellular HCV antigens. The course and outcome of HCV infection (elimination of the virus or its persistence) determines, first of all, the effectiveness of the immune response of the macroorganism. In the acute phase of infection, HCV RNA reaches high serum concentrations within the first week after infection. In acute hepatitis C (both in humans and in the experiment), the specific cellular immune response is at least one month late, the humoral response is two months late, and the virus “outstrips” the adaptive immune response. The development of jaundice (a consequence of T-cell damage to the liver) is rarely observed in acute hepatitis C. Approximately 8-12 weeks after infection, when the maximum increase in the level of ALT in the blood occurs, there is a decrease in HCV RNA titer. Antibodies to HCV are determined somewhat later and may be absent altogether, and their appearance does not mean the end of the infection. Most patients develop CHC with a relatively stable viral load, which is 2–3 orders of magnitude lower than in the acute phase of infection. Only a small proportion of patients (about 20%) recover, HCV RNA is no longer detected using standard diagnostic tests. The disappearance of the virus from the liver and, possibly, from other organs occurs later than from the blood, since the return of viremia is found in some patients and experimental chimpanzees even 4–5 months after HCV RNA has ceased to be detected in the blood. It is still unknown whether the virus disappears from the body completely. In almost all spontaneously recovered patients from acute hepatitis C, a strong polyclonal specific T-cell response can be observed, which convincingly proves the relationship between the duration and strength of the specific cellular immune response and a favorable outcome of the disease.

In contrast, the cellular immune response in patients with chronic HCV infection is usually weak, narrowly focused, and/or short-lived. The viral and host factors that cause the immune response to fail to control HCV infection are not well understood. The phenomenon of escape from the control of the immune response of the host is known, which is due to the high mutational variability of the HCV genome, resulting in the ability of the virus to long-term (possibly lifelong) persistence in the human body.

With HCV infection, a variety of extrahepatic lesions may occur due to immunopathological reactions of immunocompetent cells, which are realized either by immunocellular (granulomatosis, lymphomacrophage infiltrates) or immunocomplex reactions (vasculitis of various localization).

Morphological changes in the liver in hepatitis C are nonspecific. Predominantly lymphoid infiltration of the portal tracts is observed with the formation of lymphoid follicles, lymphoid infiltration of the lobules, stepped necrosis, steatosis, damage to the small bile ducts, liver fibrosis, which occur in various combinations and which determine the degree of histological activity and the stage of hepatitis. Inflammatory infiltration in chronic HCV infection has its own characteristics: in the portal tracts and around the foci of damage and death of hepatocytes, lymphocytes predominate, which reflects the involvement of the immune system in the pathogenesis of liver damage. Fatty degeneration is observed in hepatocytes, while liver steatosis is more pronounced when infected with genotype 3a, compared with genotype 1. Chronic hepatitis C, even with a low degree of histological activity, can accompany the development of liver fibrosis. Not only the portal and periportal zones of the lobules are exposed to fibrosis, and perivenular fibrosis is often detected. Severe fibrosis leads to the development of cirrhosis (diffuse fibrosis with the formation of false lobules), against which the development of hepatocellular carcinoma is possible. Liver cirrhosis develops in 15–20% of patients with severe inflammatory changes in the liver tissue. Currently, in addition to the morphological description of the obtained biopsy specimens, several numerical assessment systems have been developed that allow for a semi-quantitative (rank) determination of IHA - the activity of the inflammatory-necrotic process in the liver, as well as the stage of the disease, determined by the severity of fibrosis (fibrosis index). Based on these indicators, the prognosis of the disease, the strategy and tactics of antiviral therapy are determined.

Symptoms and clinical picture of hepatitis C

HCV infection leads to the development of acute hepatitis C, in 80% of cases it occurs in an anicteric form without clinical manifestations, as a result of which the acute phase of the disease is rarely diagnosed. The incubation period for acute hepatitis C ranges from 2 to 26 weeks (median 6 to 8 weeks).

Classification

By the presence of jaundice in the acute phase of the disease:
- Icteric.
- Anicteric.
According to the duration of the flow.
- Acute (up to 3 months).
- Protracted (more than 3 months).
- Chronic (more than 6 months).
By gravity.
- Easy.
- Medium heavy.
- Heavy.
- Fulminant.
Complications.
- Hepatic coma.
Outcomes.
- Recovery.
- CHC.
- Cirrhosis of the liver.
- Hepatocellular carcinoma.

The main symptoms and dynamics of their development

The clinical symptoms of acute hepatitis C do not differ fundamentally from those of other parenteral hepatitis. The duration of the preicteric period ranges from several days to 2 weeks, may be absent in 20% of patients.

In the preicteric period, asthenovegetative syndrome most often predominates, which is expressed by weakness, fatigue. Often there are dyspeptic disorders: loss of appetite, discomfort in the right hypochondrium, nausea and vomiting. Significantly less often there is an arthralgic syndrome, skin itching is possible. The icteric period proceeds much easier than with other parenteral hepatitis. The leading symptoms of the acute period are weakness, loss of appetite and a feeling of discomfort in the abdomen. Nausea and itching occur in a third of patients, dizziness and headache - in every fifth, vomiting - in every tenth patient. In almost all patients, the liver is enlarged, in 20% - the spleen.

Acute hepatitis C is characterized by the same changes in biochemical parameters as in other parenteral hepatitis: an increase in the level of bilirubin (in the anicteric form, the amount of bilirubin corresponds to normal values), a significant increase in ALT activity (more than 10 times). Often note the wave-like nature of hyperenzymemia, which is not accompanied by a deterioration in well-being. In most cases, bilirubin levels return to normal by the thirtieth day after the onset of jaundice. Other biochemical indicators (sedimentary samples, the level of total protein and protein fractions, prothrombin, cholesterol, alkaline phosphatase) are usually within normal limits. Sometimes register an increase in the content of GGT. In the hemogram, there is a tendency to leukopenia, bile pigments are found in the urine.

Acute hepatitis C occurs predominantly in a moderate form, in 30% of patients - in a mild form. The disease may be severe (rare), and fulminant acute hepatitis C, which is fatal, is very rare. In the natural course of viral hepatitis C, 20-25% of patients with acute hepatitis C spontaneously recover, the remaining 75-80% develop chronic hepatitis C. The final criteria for recovery after acute hepatitis C have not been developed, however, one can speak of spontaneous recovery if if in a patient who has not received specific antiviral therapy, against the background of good health and normal sizes of the liver and spleen, normal biochemical blood parameters are determined, and HCV RNA is not detected in the blood serum for at least two years after suffering acute hepatitis C. Factors associated with spontaneous elimination of the virus: young age, female sex and a certain combination of genes of the major histocompatibility complex.

In 70–80% of people who have had an acute form of the disease, chronic hepatitis develops, which is the most common pathology among chronic viral liver lesions. The formation of chronic hepatitis C may be accompanied by the normalization of clinical and biochemical parameters after the acute period, however, subsequently, hyperenzymemia and HCV RNA in the blood serum reappear. Most patients with biochemical signs of chronic hepatitis C (70%) have a favorable course (mild or moderate inflammatory activity in the liver tissue and minimal fibrosis).

The long-term outcome in this group of patients is not yet known. In 30% of patients with chronic hepatitis C, the disease has a progressive course, in some of them (12.5% - in 20 years, 20–30% - in 30 years) cirrhosis develops, which can be the cause of death. Decompensated liver cirrhosis is associated with increased mortality and is an indication for liver transplantation. In 70% of patients, the cause of death is hepatocellular carcinoma, hepatocellular insufficiency and bleeding. For patients with chronic hepatitis C, the risk of developing hepatocellular carcinoma 20 years after infection is 1–5%. In most cases, hepatocellular carcinoma occurs against the background of liver cirrhosis with a frequency of 1-4% per year, the 5-year survival rate of patients with this form of cancer is less than 5%.

Independent risk factors for fibrosis progression: male sex, age at the time of infection (progression is faster in patients infected over the age of 40), infection with other viruses (HBV, HIV), daily consumption of more than 40 g of pure ethanol.

Another unfavorable factor is excess weight, which causes the development of liver steatosis, which, in turn, contributes to the more rapid formation of fibrosis. The likelihood of disease progression is not related to HCV genotype or viral load.

A feature of chronic hepatitis C is a latent or asymptomatic course for many years, usually without jaundice. An increase in the activity of ALT and AST, the detection of anti-HCV and HCV RNA in the blood serum for at least 6 months are the main signs of chronic hepatitis C. Most often, this category of patients is discovered by chance, during examination before surgery, during medical examination, etc. . Sometimes patients come to the attention of a doctor only when cirrhosis of the liver develops and when signs of its decompensation appear.

Chronic HCV infection may be accompanied by normal ALT activity on repeat studies for 6 to 12 months despite continued HCV RNA replication. The proportion of such patients among all patients with chronic infection is 20–40%. In a part of this category of patients (15–20%), serious fibrotic changes can be detected during a liver biopsy. Needle biopsy of the liver is an important diagnostic method to identify patients with advanced severe liver damage in need of urgent antiviral therapy. The rate of progression of liver fibrosis in patients with normal ALT activity appears to be lower than in patients with elevated ALT activity.

Extrahepatic manifestations of hepatitis C are found, according to different authors, in 30–75% of patients. They can come to the fore during the course of the disease and determine the prognosis of the disease. The course of chronic hepatitis C may be accompanied by such immune-mediated extrahepatic manifestations as mixed cryoglobulinemia, lichen planus, mesangiocapillary glomerulonephritis, tardive cutaneous porphyria, and rheumatoid symptoms. The role of HCV in the development of B-cell lymphoma, idiopathic thrombocytopenia, lesions of the endocrine (thyroiditis) and exocrine glands (primarily, the involvement of the salivary and lacrimal glands in the pathological process, including within the framework of Sjogren's syndrome), eyes, skin, muscles, and joints has been established. , nervous system, etc.

Diagnostics

Clinical symptoms in acute hepatitis C in a significant part of patients are mild, therefore, the diagnosis of acute hepatitis C is based on a comprehensive assessment of epidemiological history data in terms corresponding to the incubation period, jaundice, an increase in bilirubin, an increase in ALT levels by more than 10 times, the presence of newly diagnosed hepatitis C markers (anti-HCV, HCV RNA) with the exclusion of hepatitis of a different nature. Considering that most patients with acute hepatitis C do not have clinical signs (symptoms) of acute hepatitis, and the available serological and biochemical manifestations do not always make it possible to distinguish acute hepatitis from an exacerbation of chronic hepatitis, the diagnosis of acute hepatitis C is established in cases where, along with characteristic clinical and epidemiological and biochemical data in the primary study of blood serum, there are no antibodies to HCV, which appear after 4-6 or more weeks from the onset of the disease. To diagnose acute hepatitis C, one can resort to the detection of viral RNA by PCR, since it can be detected already in the first 1-2 weeks of the disease, while antibodies appear only after a few weeks. The use of third-generation test systems, which are much more sensitive and specific, makes it possible to detect anti-HCV in blood serum as early as 7–10 days from the onset of jaundice. Anti-HCV can be detected in both acute hepatitis C and chronic hepatitis C.

At the same time, anti-HCV IgM antibodies are equally often detected in patients with both acute and chronic hepatitis C. Thus, the detection of anti-HCV IgM cannot be used as a marker of the acute phase of viral hepatitis C. In addition, anti-HCV can circulate in isolation in the blood of patients who have recovered from acute hepatitis C or are in remission after elimination of HCV RNA as a result of antiviral therapy. Modern test systems make it possible to increase the detection of anti-HCV in 98–100% of immunocompetent infected persons, while in immunocompromised patients the frequency of detection of anti-HCV is much lower. It is necessary to remember the possibility of false-positive results when conducting a reaction to anti-HCV, which can be 20% or more (in cancer patients, with autoimmune diseases and immunodeficiencies, etc.).

To confirm chronic hepatitis C, epidemiological and clinical data, dynamic determination of biochemical parameters, the presence of anti-HCV and HCV RNA in the blood serum are used. However, the gold standard for diagnosing chronic hepatitis C is needle biopsy of the liver, which is indicated for patients who meet the diagnostic criteria for chronic hepatitis. The goals of a puncture liver biopsy are to determine the degree of activity of necrotic and inflammatory changes in the liver tissue (determination of IHA), to clarify the severity and prevalence of fibrosis - the stage of the disease (determination of the fibrosis index), as well as to evaluate the effectiveness of treatment. Based on the results of a histological examination of the liver tissue, the tactics of managing the patient, indications for antiviral therapy and the prognosis of the disease are determined.

Hepatitis C Diagnostic Standard

Standard for the diagnosis of acute hepatitis C.
- clinical blood test;
- biochemical blood test: bilirubin, ALT, AST, thymol test, prothrombin index;
– immunological examination: anti-HCV, HBSAg, anti-HBC IgM, anti-HIV;

– immunological study: HCV RNA (qualitative analysis), anti-delta total, anti-HAV IgM, anti-HEV IgM, CEC, LE cells;
- biochemical blood test: cholesterol, lipoproteins, triglycerides, total protein and protein fractions, glucose, potassium, sodium, chlorides, CRP, amylase, alkaline phosphatase, GGT, ceruloplasmin;
- acid-base state of the blood;
- coagulogram.
- Instrumental studies:
– ECG;
- X-ray of the chest.

Standard for the diagnosis of chronic hepatitis C.
- Mandatory laboratory tests:
- clinical blood test;
- biochemical blood test: bilirubin, ALT, AST, thymol test;
– immunological examination: Anti-HCV; HBSAg;
- clinical analysis of urine and bile pigments (bilirubin).
- Additional laboratory tests:
- biochemical blood test: cholesterol, lipoproteins, triglycerides, total protein and protein fractions, glucose, potassium, sodium, chlorides, CRP, amylase, alkaline phosphatase, GGT, ceruloplasmin, iron, thyroid hormones;
- coagulogram;
- determination of blood group, Rh factor;
– immunological study: HCV RNA (qualitative analysis), anti-delta total, anti-HAV IgM, anti-HEV IgM, CEC, LE cells, anti-HBC IgM; anti-delta IgM; HBEAg; anti-HBE; HBV DNA (qualitative analysis), autoantibodies, anti-HIV, α-fetoprotein;
- stool for occult blood.
- Instrumental diagnostics (additional):
– Ultrasound of the abdominal organs;
– ECG;
- X-ray of the chest;
– percutaneous puncture biopsy of the liver;
- EGDS.

Differential diagnosis of hepatitis C

Differential diagnosis is carried out with other viral hepatitis. When making a diagnosis, they take into account, first of all, the relatively mild course of the disease characteristic of acute hepatitis C with a much lesser degree of intoxication syndrome, with a rapid normalization of biochemical parameters. Of great importance in the differential diagnosis is the dynamics of markers of viral hepatitis.

Table Differential diagnosis of acute hepatitis C with acute viral hepatitis of other etiologies and with diseases occurring with jaundice syndrome

Indications for consulting other specialists

The presence of jaundice, discomfort or pain in the abdomen, increased activity of ALT and AST, the absence of markers of viral hepatitis may require a surgeon's consultation to exclude the subhepatic nature of jaundice.

Diagnosis example

Q17.1. Acute hepatitis C, icteric variant, moderate form (HCV+ RNA, anti-HCV+).
Q18.2. Chronic hepatitis C, replicative phase (HCV RNA + genotype 3a), moderate activity (IHA 10 points), mild fibrosis (fibrosis index 1 point).

Hepatitis C treatment

Hospitalization is indicated for acute viral hepatitis and suspected viral hepatitis.

Mode. Diet

Semi-bed mode for mild and moderate acute hepatitis C. For severe acute hepatitis C, strict bed rest. In chronic hepatitis C - compliance with the regime of work and rest, work on the night shift and in industries associated with toxic products, business trips, weight lifting, etc. are not recommended.

Sparing diet (for cooking and exclusion of irritants), table number 5.

Drug therapy for hepatitis C

As an etiotropic agent in the treatment of acute hepatitis C, standard interferon alfa-2 is used. It is possible to increase the number of people who have recovered (up to 80–90%) from acute hepatitis C using the following treatment regimens:

Interferon alpha-2 5 million IU intramuscularly daily for 4 weeks, then 5 million IU intramuscularly three times a week for 20 weeks;
- interferon alfa-2, 10 million IU intramuscularly daily until the level of transaminases normalizes (which usually occurs on the 3-6th week from the start of the drug).

Effective monotherapy with pegylated interferon alfa-2 for 24 weeks.

The complex of therapeutic measures for chronic hepatitis C includes basic and etiotropic (antiviral) therapy. Basic therapy involves dieting (table No. 5), course use of agents that normalize the activity of the gastrointestinal tract, affecting the functional activity of hepatocytes (pancreatic enzymes, hepatoprotectors, choleretic agents, agents for restoring intestinal microflora, etc.).

Physical activity should also be limited, psycho-emotional and social support should be provided to patients, and comorbidities should be treated. The purpose of the etiotropic therapy of chronic hepatitis C is to suppress viral replication, eradicate the virus from the body and stop the infectious process. This is the basis for slowing down the progression of the disease, stabilizing or regressing pathological changes in the liver, preventing the formation of cirrhosis of the liver and primary hepatocellular carcinoma, as well as improving the quality of life associated with the state of health.

Currently, the best option for antiviral therapy for chronic hepatitis C is the combined use of pegylated interferon alfa-2 and ribavirin for 6–12 months (depending on the genotype of the virus that caused the disease). The standard of care for chronic hepatitis C is standard interferon alfa-2, a combination of standard interferon alfa-2 and ribavirin, and a combination of pegylated interferon alfa-2 and ribavirin. Standard interferon alfa-2 is prescribed at a dose of 3 million IU 3 times a week subcutaneously or intramuscularly, pegylated interferon alfa-2a is prescribed at a dose of 180 μg, pegylated interferon alfa-2b - at the rate of 1.5 μg / kg - 1 time per week under skin within 48 weeks for genotypes 1 and 4, within 24 weeks for other genotypes. Ribavirin is taken daily at a dose of 800-1200 mg in two doses, depending on the HCV genotype and body weight.

Establishing indications for etiotropic therapy of chronic genotype C and choosing an adequate program for its implementation are of fundamental importance. In each case, careful differentiation is needed in determining the group of individuals to be treated. According to the recommendations of the consensus conferences held in 2002, antiviral treatment should be given only to adult patients with chronic hepatitis C, the presence of HCV RNA in the blood serum and the presence of histological signs of liver damage.

Treatment may be withheld in patients with mild chronic hepatitis C who are unlikely to progress in the absence of aggravating factors (obesity, excessive alcohol consumption, HIV co-infection). In these situations, dynamic monitoring of the course of the disease is possible.

Treatment is prescribed for patients with chronic hepatitis at stage F2 or F3 according to the METAVIR system, regardless of the degree of activity of necrotic inflammation of the liver, as well as for patients with liver cirrhosis (in order to obtain a virological response, stabilize the process in the liver, and prevent hepatocellular carcinoma). After the initial course of treatment, in the absence of a virological response, but in the presence of a biochemical response, maintenance therapy with interferon alfa-2 can be prescribed to slow the progression of the disease. Predictors of treatment response in chronic hepatitis C are host factors and viral factors. Thus, patients under the age of 40 years, patients with a short duration of the disease and patients more often respond to interferon therapy. The disease responds worse to treatment in patients who abuse alcohol, patients with diabetes mellitus, liver steatosis, and obesity. Therefore, modification of the diet before starting treatment may improve its results. The response rate to treatment is higher in patients with mild fibrosis than in patients with stage 3-4 fibrosis or cirrhosis. However, in half of patients with liver cirrhosis it is possible to achieve a virological response (with genotype 1 - in 37%, with not 1 - in more than 70% of patients), therefore, this category of patients should also receive antiviral therapy, although the tactics of its implementation, if necessary, should be subject to corrections. The rate of successful virologic response with standard and pegylated interferon alfa-2, with or without ribavirin, depends on HCV genotype and viral load. Most often, patients with genotypes 2 and 3 respond to treatment, in patients with genotypes 1 and 4, the probability of a successful virological response is significantly lower. Patients with a high viral load (greater than 850,000 IU/mL) respond worse to treatment than patients with a low viral load.

Of great importance in achieving the effect during antiviral treatment is the patient's adherence to treatment. The probability of achieving the effect is higher if the patient received a full course of treatment - more than 80% of the dose of drugs for more than 80% of the intended treatment period.

Evaluation of the effectiveness of specific treatment is carried out on the basis of several criteria - virological (disappearance of HCV RNA from blood serum), biochemical (normalization of ALT levels) and morphological (decrease in the histological activity index and fibrosis stage). There are several possible responses to antiviral treatment. If the normalization of ALT and AST levels and the disappearance of HCV RNA in the blood serum immediately after the end of therapy are recorded, then they speak of complete remission, biochemical and virological response at the end of treatment.

A sustained biochemical and virological response is noted if, 24 weeks (6 months) after discontinuation of treatment, a normal ALT level is determined in the blood serum and there is no HCV RNA. Relapse of the disease is recorded when the level of ALT and AST increases and / or HCV RNA appears in the blood serum after discontinuation of treatment.

The absence of a therapeutic effect means the absence of normalization of the level of ALT and AST and / or the persistence of HCV RNA in the blood serum during the treatment. Predicting the effectiveness of ongoing antiviral therapy is possible by assessing the early virological response. The presence of an early virological response suggests the absence of HCV RNA or a decrease in viral load by more than 2×lg10 in serum after 12 weeks of treatment.

When an early virological response is recorded, the likelihood of effective antiviral therapy is high, while its absence indicates a low chance of achieving a successful virological response even if the patient's course of treatment is 48 weeks. Currently, when predicting the effectiveness of antiviral therapy, they are guided by a rapid virological response - the disappearance of HCV RNA 4 weeks after the start of antiviral treatment.

The duration of treatment depends on the HCV genotype. With genotype 1, if there is no HCV RNA in the blood serum after 12 weeks from the start of treatment, then the duration of treatment is 48 weeks. In the event that in a patient with genotype 1, the viral load after 12 weeks of treatment decreases by at least 2×lg10 compared with the baseline, but HCV RNA continues to be detected in the blood, it is necessary to re-test HCV RNA at the 24th week of treatment.

If HCV RNA remains positive after 24 weeks, treatment should be discontinued. The absence of an early virological response makes it possible to accurately predict the ineffectiveness of further therapy, and therefore treatment should also be discontinued. With the 2nd or 3rd genotype, combination therapy with interferon and ribavirin is carried out for 24 weeks without determining the viral load. With the 4th genotype, as with the 1st, combined treatment is recommended for 48 weeks. During treatment with interferon drugs and ribavirin, adverse events are possible.

A prerequisite for ribavirin therapy is the use of contraception by both partners during the entire period of treatment (it is also recommended to avoid pregnancy for another 6 months after the end of the course of treatment). Side effects of interferon and ribavirin sometimes force them to reduce their doses (temporarily or permanently) or stop the drugs. During treatment, patients should be monitored, biochemical control should be carried out (every two weeks at the beginning of treatment, then monthly), virological control (for genotype 1 - after 12 weeks from the start of therapy, for genotype 2 or 3 - at the end of treatment). In some cases, at the end of the course of treatment, a repeated puncture biopsy of the liver is performed to assess the histological picture.

Examine the hemogram, once every four months - the concentration of creatinine and uric acid, TSH, ANF.

Due to the presence of common routes of transmission of viruses, chronic hepatitis C is often accompanied by infection with HBV and/or HIV. Co-infection increases the risk of developing liver cirrhosis, terminal hepatocellular insufficiency and hepatocellular carcinoma, as well as patient mortality compared with that of patients with HCV monoinfection. Preliminary data suggest that the combination of pegylated interferon and ribavirin achieves a virological and/or histological response in HIV-infected patients with chronic hepatitis C. When antiviral therapy is prescribed for patients with chronic viral hepatitis with mixed infection, the choice of treatment regimen determines the presence of the HBV replication phase and HCV.

The principles of pathogenetic and symptomatic therapy for acute hepatitis C are the same as for other viral hepatitis. Against the background of physical rest and diet (table No. 5), detoxification therapy is carried out in the form of heavy drinking or intravenous infusions of 5-10% glucose solution, polyionic solutions and ascorbic acid. According to individual indications, protease inhibitors, antispasmodics, hemostatic agents, hyperbaric oxygenation, hemosorption, plasmapheresis, laser therapy are used.

Forecast

The prognosis for acute hepatitis C has improved significantly with the introduction of antiviral therapy, the timely administration of which allows recovery in 80–90% of patients. In the event that it was not possible to diagnose the acute phase of the infection and patients do not receive antiviral therapy, the prognosis is worse - 80% of patients develop chronic hepatitis C, 15–20% of patients with a progressive course of the disease may develop liver cirrhosis within 20–30 years. Against the background of cirrhosis of the liver with a frequency of 1-4% per year, primary hepatocellular carcinoma occurs.

Clinical examination

The peculiarity of medical examination of patients with viral hepatitis C is the duration of the procedure.

Patients with hepatitis C are observed for life due to the lack of reliable criteria for recovery in order to timely detect signs of infection reactivation and correct the tactics of observation and treatment.

Reminder for the patient

You have had acute hepatitis C and you need to know that the disappearance of jaundice, satisfactory laboratory results and good health are not indicators of complete recovery, as full recovery of liver health occurs within 6 months. To prevent exacerbation of the disease and the transition to a chronic form, it is important to strictly follow medical recommendations related to follow-up and examination in a clinic, daily routine, diet, and working conditions.

Mode. Diet

Return to work activity associated with great physical stress or occupational hazards is permissible no earlier than 3–6 months after discharge. Prior to this, it is possible to continue working in the mode of light work.

After discharge from the hospital, one should beware of hypothermia and avoid overheating in the sun; trips to southern resorts are not recommended during the first 3 months. You should also beware of taking medications that have a side (toxic) effect on the liver. After the normalization of biochemical parameters of blood for 6 months, participation in sports competitions is prohibited. Those who have recovered from acute hepatitis C are exempted from preventive vaccinations for 6 months. Sports activities are limited only by a complex of therapeutic exercises.

For 6 months after discharge, special attention should be paid to nutrition, which should be sufficiently complete, with the complete exclusion of substances harmful to the liver. Alcoholic drinks (including beer) are strictly prohibited. It is necessary to eat regularly every 3-4 hours during the day, avoiding overeating.

Allowed:

Milk and dairy products in all forms;
- boiled and stewed meat - beef, veal, chickens, turkey, rabbit;
- boiled fresh fish - pike, carp, pike perch and sea fish (cod, perch);
- vegetables, vegetable dishes, fruits, sauerkraut;
- cereals and flour products;
- vegetable, cereal, milk soups;

You should limit your use of:

Meat broths and soups (low-fat, no more than 1-2 times a week);
- butter (no more than 50-70 g per day, for children - 30-40 g), cream,
sour cream;
- eggs (no more than 2-3 times a week protein omelettes);
- cheese (in a small amount, but not spicy);
- meat products (beef sausages, doctor's, dietary, canteen sausages);
- caviar of salmon and sturgeon, herring;
- tomatoes.

Forbidden:

Alcoholic drinks;
- all kinds of fried, smoked and pickled products;
- pork, lamb, goose, duck;
- spicy seasonings (horseradish, pepper, mustard, vinegar);
- confectionery (cakes, pastries);
- chocolate, chocolates, cocoa, coffee;
- tomato juice.

Medical supervision and control

Examination of those who have had viral hepatitis C is carried out after 1, 3, 6 months, and then, depending on the conclusion of the dispensary doctor. Deregistration with a favorable outcome is carried out no earlier than 12 months after discharge from the hospital.

Remember that only the observation of an infectious disease specialist and regular laboratory examinations will allow you to establish the fact of your recovery or the transition of the disease to a chronic form. If your doctor prescribes antiviral treatment, you must strictly adhere to the regimen of administration of the drug and regularly come to the laboratory control of blood counts, as this will minimize the likelihood of side effects of the drug and ensure infection control.

It is necessary to appear for a laboratory examination on the day strictly prescribed by the doctor on an empty stomach.

Your first visit to the KIZ polyclinic is appointed by the attending physician. The established deadlines for repeated medical examinations in a polyclinic or a hepatological center are mandatory for all those who have had hepatitis C.

If necessary, you can contact the follow-up room of hospitals, or the hepatology center, or the QIZ polyclinic also in addition to these terms.

Be attentive to your health!
Strictly follow the regimen and diet!
Get regular medical checkups!

Prevention of hepatitis C

There is no specific prevention, since the pronounced variability of the HCV genome creates serious difficulties for creating a vaccine.

Non-specific prevention of viral hepatitis C, as well as other parenteral hepatitis, includes the improvement of a set of measures aimed at preventing parenteral infection in medical and non-medical institutions, strengthening the fight against drug addiction, improving public awareness of the ways of transmission of the hepatitis C pathogen and measures to prevent infection with this virus .

After hospitalization of the patient, the final disinfection is carried out. Contacts are examined in a laboratory to identify infected individuals.

Hepatitis is an acute or chronic inflammatory disease of the liver that occurs as a result of infection with specific viruses or exposure to toxic substances (for example, alcohol, drugs, drugs, poisons) on the organ parenchyma. In addition, inflammatory processes in the liver can be autoimmune in nature.

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The problem of hepatitis is very relevant due to the wide spread of this disease among people, its frequent asymptomatic course and high risk of infection (this applies to infectious hepatitis). In addition, the fact that a long-term inflammatory liver disease can result in the development of irreversible fibrotic changes in the organ and a pronounced one, which is practically untreatable, makes this problem especially serious.

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Varieties of hepatitis

Depending on the cause of the disease, the following types of hepatitis are distinguished:

infectious or viral. There are five main types of hepatitis viruses (A, B, C, D, and E) that can cause liver inflammation. In addition, hepatitis can be one of the manifestations of other infectious diseases - rubella, etc.
toxic. These include medicinal, alcoholic and hepatitis developing in case of poisoning with industrial and vegetable poisons. Among the drugs, antiviral, sulfanilamide drugs, antipyretics (paracetamol, ibuprofen), anticonvulsant and antitumor drugs have a special hepatotoxicity.
Autoimmune, in which, for reasons unknown to medicine, it begins to attack its own hepatocytes (liver cells).

Depending on the characteristics of the flow, distinguish two forms of the disease:

Acute hepatitis. It develops suddenly, accompanied by symptoms of intoxication, fever, jaundice (but not always). According to this scenario, most viral hepatitis and toxic hepatitis develop, caused by poisoning with some strong poisons. If the patient undergoes the necessary treatment in a timely manner, after an acute illness, in most cases, recovery occurs.
chronic hepatitis. It may result from acute viral hepatitis, autoimmune processes, alcohol abuse, or long-term treatment with hepatotoxic drugs. In addition, viral hepatitis B and C can develop immediately as a primary chronic disease. Chronic hepatitis occurs, usually without severe symptoms, so it is often diagnosed when there is already serious damage in the liver.

What happens with hepatitis?

The mechanism of development of infectious and non-infectious hepatitis is somewhat different. In viral hepatitis B, viruses invade liver cells and change the set of protein structures on their surface, so the immune system begins to kill hepatocytes. The more viruses are introduced into the cells, the more extensive damage to the liver occurs. Further, the normal liver parenchyma is replaced by connective tissue, that is, cirrhosis complicates hepatitis. In this case, the function of the organ cannot but suffer. The detoxification ability of the liver is most noticeably disturbed, as a result of which bilirubin and other toxic substances accumulate in the body.

Hepatitis C develops according to a slightly different mechanism: viruses damage hepatocytes on their own, so with this disease, fibrotic changes in the liver appear faster, and the risk of cancer increases many times. With toxic hepatitis caused by strong poisons, liver damage can be fulminant, accompanied by massive necrosis of the organ.

Drug-induced hepatitis also has different mechanisms of development, since each drug has its own specific effect. For example, some block enzymes and disrupt the biochemical processes occurring in hepatocytes, others damage the cell membrane and intracellular structures (mitochondria), etc.

In chronic cases, fatty degeneration of the liver develops first, and already at the next stage - hepatitis. In addition, acetaldehyde (a product of ethanol metabolism) has a pronounced toxic effect on hepatocytes, so if a lot of it is formed, for example, with severe alcohol poisoning, organ necrosis may develop.

Can you get hepatitis?

Only viral hepatitis is contagious. Moreover, they can become infected in different ways:

Through dirty hands, dishes, contaminated water and food. This is how hepatitis A and E are transmitted.
Through contact with the patient's blood. In this regard, many medical and dental procedures, manicure, pedicure, tattooing, piercing, injecting drug use, etc. are dangerous. This route of transmission is typical for viral hepatitis B, C, D.
Sexually. Semen and vaginal secretions of patients with hepatitis B, C, D can also contain viruses. The risk of infection is especially high in homosexual relationships.

Hepatitis symptoms

The first signs of acute hepatitis:

Increase in body temperature.
Soreness and heaviness in the right hypochondrium.
Jaundice of the skin and eyes.
Discoloration of feces.
Skin itching.
Nausea.
Darkening of the urine.
Marked weakness.

However, it should be noted that the presence of these features is not required. In mild cases, the disease can begin unnoticed by the patient - just like a mild ailment.

Chronic hepatitis is asymptomatic much more often than acute hepatitis.. Patients often learn about the disease in the process of some planned examinations. If there are symptoms, then they are usually unexpressed and non-specific. So, patients may be concerned about:

Feeling of heaviness and fullness in the right side, worse after eating.
Tendency to bloating.
Periodic nausea.
Loss of appetite.
Increased fatigue.

If the described symptoms occur, it is necessary to contact a therapist, an infectious disease specialist or a hepatologist.

Diagnosis of hepatitis

To diagnose hepatitis and identify its cause, the patient needs to conduct a comprehensive examination:

Clinical examination(the doctor may detect an increase in the liver, a change in the color of the skin and mucous membranes).
Ultrasound of the abdomen.
Laboratory analysis for hepatitis. If viral hepatitis is suspected, it is necessary to look for markers of hepatitis in the blood. For this, two methods are used - , . If autoimmune inflammation of the liver is suspected, antibodies to the cellular structures of hepatocytes (nucleus, microsomes, plasma membrane antigens, etc.) are looked for.
Biochemical blood test, which makes it possible to identify signs of dysfunction of the organ and the destruction of its cells. The patient is analyzed for the so-called liver tests (ALT, AST, total, direct and indirect, alkaline phosphatase, proteins).
Liver biopsy. This diagnostic method allows you to accurately assess the condition of the liver (are there signs of inflammation, sclerosis, etc.).

Principles of treatment

In the treatment of any hepatitis, three points are important: properly selected drug therapy, diet and the rejection of all unhealthy habits.

Medical treatment has two goals:

Eliminate the cause of the disease.
Restore liver function and prevent further organ damage.

The therapy intended to fulfill the first point is determined by the etiology of hepatitis:

if the viral nature of the disease is proven, the patient is prescribed antiviral drugs and interferons;
if toxic - specific antidotes, sorbents, detoxification therapy;
if autoimmune - glucocorticosteroids.

To restore liver function and protect the organ from harmful effects, hepatoprotectors are prescribed. There are a large number of such drugs, the active ingredient in them can be one of the following substances:

Silymarin is derived from milk thistle. This substance stops the processes of peroxidation and destruction of hepatocytes.
Essential phospholipids, which are elements of hepatocyte cell membranes, contribute to their restoration and normalization of metabolic processes in liver cells.
Ornithine. It protects not only liver cells, but also cleanses the body of toxins.
Lecithin (it is also a phospholipid).
Ademetionine is a substance derived from the amino acid methionine, which normalizes the biochemical processes occurring in the liver.

diet for hepatitis

Basic rules of the diet indicated for hepatitis.

REVIEWER
Head of the Department of Surgery, Zaporozhye State Institute for Postgraduate Medical Education, Professor, MD V.G.Yareshko

Accepted abbreviations:
AST - alcoholic steatosis hepatitis
HBV - hepatitis B virus;
HCV - hepatitis C virus;
HDV - hepatitis D virus;
HGV - hepatitis G virus;
VH - viral hepatitis,
HBV - viral hepatitis B,
HCV - viral hepatitis C,
HDV - viral hepatitis D,
VGG - viral hepatitis G;
HCC - hepatocellular carcinoma
IF - interferon;
IT - interferon therapy;
CP - cirrhosis of the liver;
CG - chronic hepatitis
AP - alkaline phosphatase

INTERPRETATION OF THE CLINICAL PICTURE IN HEPATOLOGY

Complaints are of a general nature for a variety of liver damage: asthenia (fatigue, decreased performance, sleep disturbance), dyspepsia, in more severe cases, itching, bleeding, flatulence that is little dependent on food intake. HCV infection in the CNS is thought to be the cause of complaints of fatigue in HCV patients. Pain syndrome can be associated with liver pathology, but more often - with stretching of the liver, biliary dyskinesia, non-ulcerative dyspepsia syndrome.

From the anamnesis of patients with chronic hepatitis, the medications taken, the doses and duration of alcohol and drugs intake are taken into account. The onset of the disease, for example, with CHC, cannot be established in most cases.

Inspection of patients begins with the search for jaundice, which is found most early in the soft palate. A rash is being searched as a manifestation of intoxication, traces of injections in drug addiction. "Small liver signs" - "liver stars", red palms, white nails - do not allow diagnosing CG with certainty.
Violation of secondary sexual characteristics develops in the later stages of CP. The rounded edge of the liver is characteristic of steatosis, pointed - hCG, and uneven, tuberous - cirrhosis, HCC. A false conclusion about the “tuberosity” of the liver can be made with unevenly developed abdominal muscles, lipomatosis. The position of the edge of the liver below the costal arch can be due to many reasons. Borders of the liver according to Kurlov: 10-8-7±1-2cm. has an indicative value. Normally, the amount of fluid in the abdominal cavity reaches 150 ml. Objectively, it is impossible to detect the amount of liquid less than 1.5-3 liters.

Clinical symptoms in chronic hepatitis do not reflect the severity of the process. With histologically severe CG, there may be no complaints.

INTERPRETATION OF BIOCHEMICAL TESTS IN HEPATOLOGY

Aminotransaminases (ALT, AST) are a sensitive test for liver damage (cytolysis syndrome), second only to morphological. They are the main criterion for the activity of CG. For HCV, fluctuations in ALT are characteristic, with the presence of normal values in morphologically active hepatitis. In this case, to assess the value of transferases, they must be examined within 6 months. The value of ALT, AST in patients with cirrhosis reflects the activity of concurrent CG.

An increase in the de Ritis index (the ratio of AST / ALT, normally 0.7) indicates alcohol abuse. The predominance of ALT activity over AST is typical for viral hepatitis, AST over ALT (above 1, usually about 2) - for ACH and HCC. AST/ALT ratios greater than 1 can be considered as a threat criterion for cirrhosis in HCV. Moreover, the value of the coefficient is determined by the severity of fibrosis, but not by the activity of inflammatory changes in the liver.

Alkaline phosphatase (AP) and β-glutamyl transpeptidase (GGTP) increase with cholestasis, cancer, steatosis, amyloidosis, in addition, ALP - with pathology of bones, placenta, fallopian tubes, GGTP - with prolonged alcohol use. In the study of GGTP, there are many false positive results associated with concomitant diseases, medication. With the development of acute obstruction of the biliary tract, enzymes increase with a 1-3-day delay.

Synthetic liver function tests (prothrombin, albumin) change with a decrease in liver function by more than 90%.

Coagulation (sedimentary) tests - thymol, etc. - reflect the ratio of globulins to albumins and blood lipids. Not specific, increase with collagenosis, infectious diseases, pneumonia, nephritis.

Markers of hepatitis viruses indicate the presence of infection, not characterizing the state of the liver. Negative marker test results are sufficient to rule out CH. Recently, mutant viruses have been discovered (in particular, the HBeAg-negative HBV mutant), which may not be detected in the blood serum, but are found in the liver tissue and outside it.

Diagnosis of HBV: the main marker is HbsAg, HBV DNA. The presence of HBeAg indicates the activity of viral replication. The disappearance of HBeAg and the appearance of antibodies to it (anti-HBe) registers the cessation of HBV replication and is interpreted as a state of partial seroconversion. There is a direct relationship between CHB activity and the presence of viral replication and vice versa.

HCV: antibodies to HCV - anti-HCV. The presence of a current infection is confirmed by the detection of HCV RNA (HCV RNA). Anti-HCV is detected in the convalescent phase and ceases to be detected 1-4 years after acute CH. Its presence after this period is indicative of chronic hepatitis, although its absence in serum does not exclude HCV infection.

HDV: HBsAg + anti-HDV-anti-HDV, complemented by HDV RNA.
HGG: viral RNA - HGV RNA.

INSTRUMENTAL DIAGNOSIS IN HEPATOLOGY

The only research method that allows to verify liver disease is morphological. A liver biopsy followed by a morphological study is indicated for diagnosis, determining the severity of CH, and treatment tactics. The clinic and laboratory tests are often not correlated with morphological changes in the liver. Liver biopsy is not indicated: with hemorrhagic diathesis or other serious diseases, in the absence of indications for treatment (age, etc.). The modern technique of taking liver biopsies (under ultrasound control) has reduced the frequency of complications to hundredths of a percent.

The possibilities of sonography in hepatology are often overestimated. Modern ultrasound technique provides for: 1) conducting a survey ultrasound of the abdominal cavity, and not just the target organ”; 2) repetition of ultrasound as an integral element of dispensary observation.

Fatty hepatosis is diagnosed according to sonography in 100% of cases by total hyperechogenicity and a rounded edge of the liver. ASH is characterized by fatty degeneration, hepatomegaly, and ascites can be recorded at the height of exacerbation.

Drug-induced hepatitis has no characteristic signs, but its development can be predicted. by reducing the diameter of the hepatic veins with the appearance of hepatomegaly.

CG does not have reliable ultrasound signs. The most commonly used criteria - hyperechogenicity, heterogeneity of the echostructure - are evaluated subjectively, which makes them unreliable. With an exacerbation of chronic hepatitis, the degree of narrowing of the hepatic veins (up to 5-8 mm) corresponds to the severity of the disease. An unfavorable sign of chronic hepatitis is the appearance of portal hypertension or an increase in the diameter of the portal vein with a decrease in the hepatic veins. Expansion of the portal and splenic veins is detected in 35% of patients with chronic hepatitis. In severe exacerbation of CHC, ascites may be recorded. More than half of patients with CG have wall thickening and hypomotor dyskinesia of the gallbladder, thickening of the pancreas.

Ultrasound is reliable in the diagnosis of cirrhosis: sonographic and morphological findings coincide in a significant number of cases. In the early stages of cirrhosis, the size of the liver may be normal, but the structure may be patchy or even normal. A change in the normal Doppler curve in the hepatic veins is the earliest sign of cirrhosis (in class A according to Child-Pugh).

SONOGRAPHIC CRITERIA

Liver changes: Decrease in liver size with enlargement of the left lobe: the ratio of the transverse diameter of the caudal lobe of the liver to the right lobe of 0.65 is considered to be specific and moderately sensitive for the diagnosis of cirrhosis. However, it is easier to measure the ratio of the anterior-posterior dimensions of the caudate and left lobe (the diagnostic value is 0.5).

Acoustic heterogeneity of the liver with a moderate increase in echogenicity.

Irregularity of the contours of the liver.

Absence of echographic dynamics within 1 month

Extrahepatic changes (usually due to portal hypertension):
Splenomegaly (spleen size more than 13 cm).
Increased portal vein diameter > 13 mm.
An increase in the diameter of the splenic vein > 10 mm.
The formation of porto-systemic shunts - short veins of the stomach, coronary vein, lieno-renal and paraumbilical veins.

Ascites. Against the background of ascites, the nodular surface of the liver comes to light better.

With the exclusion of a neoplasm, severe acute hepatitis, rare diseases (Buddy-Chiari, thromboembolism of the liver vessels, etc.), the presence of portal hypertension indicates cirrhosis. Doppler ultrasound can detect diagnostically significant changes in blood flow in the portal and hepatic veins.

The cirrhosis is accompanied by the appearance of regeneration nodes, which is recorded as a deformation of the liver contour. Detectability in cirrhosis of large-wavy irregularities of the liver contour (5-15 mm) is up to 100%, and fine-wavy up to 70%. A targeted examination of the surface of the liver using a 7.5 MHz sensor has a high sensitivity (more than 80%).

Fibrosis of the liver is often accompanied by fatty infiltration, which leads to increased echogenicity of the liver. In the absence of fatty infiltration, the echogenicity of a fibrously altered liver differs little from the norm. The size of the liver can be normal or reduced, the surface is even.
The accuracy of ultrasound in relation to the diagnosis of tumors (metastases) of the liver reaches 80%. Dynamic monitoring (1 time in 2 months for six months) increases the likelihood of cancer diagnosis.
Magnetic nuclear resonance and computed tomography are mainly used in the diagnosis of cancer. In terms of accuracy, they are close to ultrasound tomography, their combined use is more informative.

CHRONIC VIRAL HEPATITIS

It is believed that in 70-80% of cases CG is viral. In the structure of the incidence of viral CG in Western Europe and the USA, HCV belongs to 60-80%, HBV - 10-30%, cryptogenic CG - up to 10-25%. 65% of them are in the 30-49 age group. HCV is infected by 1.8% of Americans. The prevalence of viral CG among healthcare workers is higher than in the general population. The highest risk are employees of hemodialysis units, intensive care units, surgeons, nurses and laboratory assistants.

Ukraine is considered a country with a moderate prevalence of CG. In total, 7.8% of the population of regional centers and up to 5% in the region are infected. In 1999-2000, the average frequency of detection of markers among donors in Ukraine was HBsAg-1.1%. Hepatitis markers are detected: HbcAg-1-2%, anti-HCV-6-3%. In 23% of cases, the etiological factor is HCV (genotype 1b prevails (85%), in 43% - HBV, in 1% - HDV. The frequency of detection of viral chronic hepatitis markers is higher at the age of 30-34 years (6.98%), and in men (4.04%) than women (2.12%).

FREQUENCY OF HEPATITIS MARKERS DETECTION IN ZAPORIZHIA, 1994-1998

Contributes to the acquisition of infection drug use, high-risk sexual behavior, as well as poverty, inadequate education, marriage breakdown, contact with blood. HCV RNA was found in semen, ascitic fluid. The possibility of infection through household contact is small or absent. The risk of contracting HBV is 100 times greater than HIV because it is more viable. Carriers of hepatitis viruses is one person out of 20, which is a danger to others. Compared to HIV, HCV is more likely to be transmitted through blood contact and less likely to be transmitted sexually.

Ways of infection with hepatitis viruses:
. Drug addiction (the leading route of infection in adolescents). The risk of HBV and HCV infection among people who use drugs is 60-90%, while on average among the population it does not exceed 5%.
. Hemotransfusions and transfusion of blood products, injections, multiple hemodialysis (through mucous membranes or blood entering the mucous membrane of the eye);
. Dental procedures, diagnostic and therapeutic medical procedures (colonoscopy, laparoscopy, etc.)
. vertical transmission (mother to child)
. Sexual route (for HBV-25-50%): increases dramatically with the number of sexual partners, homosexuality, oral sex.
. Emigrants from Asia and Africa.
The progression of viral CG to fibrosis and cirrhosis is accelerated by alcohol, male homosexuality, infection over 40 years and mixed infection with HIV and/or another hepatitis virus.

PATHOGENESIS OF CHRONIC VIRAL HEPATITIS

The half-life of HBV in plasma is 24 hours, the daily turnover of the virus is more than 50%, reproduction is more than 1011 copies / day. The persistence of various CG viruses is carried out using common mechanisms, but each infection is characterized by the predominance of certain factors. The possibility of extrahepatic replication of HCV and HBV, in particular in immunocompetent organs - monocytes, has been proven. In this case, the viruses become inaccessible to immune control. HCV is characterized by the ability to mutate. HCV surface antigens are updated in minutes. Due to this hypervariability, the reproduction of HCV occurs as a symbiosis of a large number of immunologically delimitable strains. There is a constant "competition for speed" between the formation of new antigenic variants and the mechanisms of their neutralization, in which the virus wins. A particularly high mutation rate is inherent in the HCV 1b genotype, which is predominant in Europe. Suppression of interferon production is characteristic of HBV.

In the implementation of the damaging effect of hepatitis viruses on the liver and other organs, cytokines, activated macrophages, interleukin-1 are involved with the development of destruction of the connective tissue matrix of the liver. Viruses do not directly participate in damage to hepatocytes, and T-lymphocytes and macrophages play the leading role. Liver macrophages are "conductors" of fibrosis, and collagen producers - fibroblasts - are its executors. Another mechanism of cell death, apoptosis (self-programmed cell death), is being actively studied.

CLASSIFICATION OF LIVER DISEASES(Los Angeles, 1994) is based on etiological and clinical-morphological principles. The leading idea is the recognition that CG in its development goes through several morphological stages up to the formation of the CP as the final, irreversible stage of a single process.
I. The following diseases are classified as chronic hepatitis:

1. Chronic viral hepatitis B (HBV), D (HDV), C (HCV);
2. Indefinite chronic viral hepatitis.
3. Autoimmune hepatitis (types 1, 2, 3).
4. Drug-induced chronic hepatitis.
5. Cryptogenic hepatitis (of unknown etiology).
The inclusion of primary biliary hepatitis, primary sclerosing cholangitis, and Wilson-Konovalov disease in the classification of CG remains controversial.

II. Definitions (definitions) of diseases.

1. Chronic viral hepatitis B (C): an inflammatory disease of the liver caused by HBV (HCV) lasting 6 months or more and capable of leading to cirrhosis or being associated with cirrhosis. The latter means the following: - CHB (CHC) joins an existing cirrhosis of a different etiology, - CHB (CHC) proceeds in parallel with the cirrhosis of the same nature and determines the degree of activity of the process (not a stage!). (The period of 6 months is defined for cases where there is no acute onset of the disease or CG develops imperceptibly).

2. Chronic drug-induced hepatitis: Inflammatory liver disease lasting 6 months or more due to side effects of a drug (direct toxic effect of the drug or its metabolites, or an idiosyncratic reaction to the drug). The reaction of idiosyncrasy is manifested either by metabolic disorders or by an immunoallergic response.

III. The etiological component should be included in the diagnosis of CG and cirrhosis in all possible cases.

IV. The severity of the course is determined by the stage of chronic hepatitis, the criterion of which is the prevalence of fibrosis in the liver and the development of cirrhosis (according to morphological data). Stages of CG are distinguished from 0, when fibrosis is absent, to IV, when cirrhosis has already formed.

V. Morphologically distinguish persistent, active, lobular hepatitis; Small-nodular (micronodular) and large-nodular (macronodular) CP. The morphological component can be used as a diagnosis if it can be associated with a causative factor. Acceptable: micronodular cirrhosis, the cause has not been established. Unacceptable: micronodular cirrhosis.

VI. In cirrhosis, the severity and stage of the disease is determined by the severity of portal hypertension and hepatocellular insufficiency.

VII Clinically, the activity of the necroinflammatory process in the liver is assessed by the levels of ALT and distinguish between: - "mild" form of CG - ALT< 3 норм; - умеренную - АЛТ от 3 до 10 норм; - тяжелую - более 10 норм.

With a significant severity of the syndrome in the diagnosis, one can indicate: with cytolytic, cholestatic, immune-inflammatory, with ascites or hypersplenism syndromes.

Alcoholic liver disease is discussed under the heading "alcoholic liver disease". A special place is occupied by liver lesions that develop with collagen diseases ("granulomatous" hepatitis), severe diseases of the digestive system (reactive "hepatitis"). This pathology is not classified as CG, since the morphological changes in this case do not correspond to CG.

In European countries, to assess the severity of cirrhosis, the Child-Pugh scale (Chidl-Pugh) is usually used, which has also begun to be used in Ukraine.

CHILD-PUG SCORE OF LIVER CIRRHOSIS Severity

Criteria for assessing the Child-Pugh scale: 5-6 points - class A (compensation); 7-9 points - class B (subcompensation); 10 or more points - class C (decompensation).

The interpretation of the diagnosis of hepatitis-cirrhosis implies the presence of signs of cirrhosis, primarily according to the morphological study. In these patients, two processes usually proceed in parallel: CG and cirrhosis, which cannot be differentiated. However, the presence of clinical signs of cirrhosis is not necessary.

TOPIC: VIRAL HEPATITIS.

Hepatitis is an inflammation of the liver parenchyma (hepatocytes) and stroma (stellate endotheliocytes, or Kupffer cells).

Hepatitis is:

non-specific (reactive, that is, as a reaction of liver cells to inflammation of neighboring organs - the pancreas, gallbladder, duodenum). Very often, reactive hepatitis develops in patients with chronic pancreatitis, in patients suffering from duodenal ulcer.

Nonspecific viral hepatitis - hepatitis caused by a group of viruses that can affect the liver, including other organs, that is, viruses that have tropism for other organs and tissues have a tropism for liver tissue. For example, the infectious mononucleosis virus (Epstein-Barr virus). This virus selectively affects the cells of the reticuloendothelial system (hence the occurrence of tonsillitis, hypersplenism, hepatitis, and other diseases). Adenovirus causes pharyngoconjunctival fever, acute pneumonia, hepatitis. Enteroviral hepatitis often occurs in the summer. Herpes simplex virus is an AIDS-defining infection.

Hepatitis associated with the use of drugs - toxic-allergic and drug-induced hepatitis. Alcoholic hepatitis (chronic alcoholic hepatitis is a combined lesion with acetaldehyde and some other factor).

Hepatitis as a manifestation of an etiologically independent disease - leptospirosis (leptospira has hepatotropic, hematotropic properties). Pseudotuberculosis - Yersinia has a tropism for RES cells.

specific viral hepatitis.

This group of viral lesions of the liver is caused by numerous types of DNA and RNA-containing viruses, characterized by the development of infiltrative-degenerative changes in the liver tissue with the appearance of a pronounced intoxication syndrome, which is a consequence of the current cytolysis and cholestatic syndrome, the manifestation of which may be jaundice, hepatomegaly, pruritus, changes in urine color and feces.

Specific viral hepatitis is caused by a group of viruses that are divided into two groups - DNA and RNA containing viruses, and DNA-RNA virus (hepatitis B virus).

Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, hepatitis G virus (discovered in 1994, finally identified in late 1995), Dale (Amer.) isolated a new virus - GB (under the initials patient). There are several types of GB virus - GBH, GBS, GBD. Hepatitis F virus, V virus. So there are ten hepatitis viruses in total.

All hepatitis caused by these viruses can be divided into two groups - viral hepatitis that is transmitted by the fecal-oral route (infectious hepatitis, which is transmitted directly from person to person during communication, when the virus is released into the environment with feces) and serum hepatitis with a blood-contact transmission mechanism.

Nucleic acid content	transmission path	the likelihood of vertical infection (transplacental).	stability in the external environment	chroniogenicity of the virus	the possibility of developing hepatocellular cancer
Hepatitis A virus	RNA	fecal-oral route	No	+++	1%	does not possess
hepatitis b virus	RNA	blood contact	+++ (depends on the phase of virus replication during pregnancy, childbirth	+++++	to 10%	+++
hepatitis C virus	RNA	blood contact	+++	+	50-95%, drug addicts 100%	+++
hepatitis D virus	RNA-DNA	blood contact	not studied	+++++	80%	+++
hepatitis E virus	RNA	fecal-oral	not studied	+++	practically 0	No
hepatitis G virus	DNA	blood contact	not studied	unknown	50-95%	unknown
hepatitis F virus	No data	unknown	not studied	unknown	No data

Hepatitis A virus. Hippocrates also wrote about the disease, he suggested using various objects with a patient suffering from hepatitis. The dispute about the cause of infectious hepatitis has lasted since the last century, and was resolved when S.P. Botkin managed to refute Virchow's theory of the catarrhal nature of hepatitis. Virchow believed that mechanical obstruction of the bile ducts is primary, followed by inflammation of the ducts, an increase in the lithogenicity of bile. Bile creates a plug in the ducts, dystrophy develops as a result of insufficient blood supply, and all the phenomena of hepatitis. But for some reason, it was always revealed at the autopsy that the process went from the central vein, that is, from the center to the periphery.

Since Botkin proved the infectious nature of hepatitis, this disease has been called Botkin's disease. This name lasted until 1974. The virus was isolated in 1945, at the same time its properties were studied. This virus was assigned to the group of picornaviruses. In 1958, the details of the virus were finally studied - an RNA-containing virus, with a fecal-oral transmission mechanism, belongs to the group of enteroviruses. Prof. Balayan revealed that marmazets also have sensitivity to the hepatitis A virus, which served as an experimental model for studying the disease.

The virus is quite stable in the external environment, absolutely resistant to low temperatures (for years), which is used to store sera containing viruses. Dies only when autoclaved and at 100 degrees for 10 minutes. Hepatitis is thus a commonplace intestinal infection with a fecal-oral transmission mechanism. The source is a sick person, the patient is most dangerous at the end of the incubation period and in the first days of the icteric period (it is during this period that the patient is at home), when the hepatitis A virus is excreted with feces into the external environment in large quantities. The infection transmission factor is food (there were sour cream outbreaks, oyster outbreaks are described), water (water outbreaks are described, which is also indicated by the nature of the process - a one-time surge in incidence, and then a rapid decline). The contact-household way is possible (especially in children's institutions). A theory about the possibility of aerogenic infection has been put forward. Possible parenteral route (transfusion). as a rule, children and young people get sick because the immunity is extremely persistent after the disease and in fact every adult over 40 years of age has met with this infection (has suffered erased or manifest forms). Mandatory vaccination against hepatitis A has now been introduced (in England, in the USA).

For viral hepatitis A, as for an intestinal infection, seasonality is characteristic, the possibility of developing epidemic outbreaks. This is a cyclically occurring disease with rigidly defined periods that are characteristic of an infectious disease.

The incubation period is up to 45 days (minimum 8-12 days). Then comes the pre-icteric period, which usually proceeds according to a catarrhal or flu-like type. In addition, an arthralgic variant, dyspeptic, asthenovegetative, asymptomatic, mixed is possible. The duration of the preicteric period is from 1 to 7 days (usually 3-5 days). This is followed by an icteric period that lasts up to 10-12 days, the disease usually ends in recovery, the mortality rate is low (0.1%). formation of chronic hepatitis in 1% of patients. After that, a period of early convalescence begins, so patients are under dispensary observation for up to 6 months. Then comes a period of late convalescence - up to 1 year, when virus replication is still possible, and the patient requires periodic monitoring of the local therapist and adherence to the diet.

PATHOGENESIS OF VIRAL HEPATITIS A.

Blucher put forward the immunogenetic concept of pathogenesis. The first phase - the phase of the introduction of the pathogen - the pathogen enters the body. It reaches the small intestine, where it penetrates into enterocytes with the development of the enteral phase of viral hepatitis. There is baldness of the apical side of enterocytes, a decrease in villi. Settling in the cells, the virus penetrates into Peyer's patches and solitary follicles and then moves to the mesenteric lymph nodes - the third phase - the phase of regional lymphadenitis. In the mesenteric lymph nodes, the virus multiplies, accumulates to pathogenic quantities and breaks through the lymphatic thoracic duct into the bloodstream and the primary generalization phase of the infection begins. The virus is introduced into all organs and tissues, but since the virus does not carry a specific hepatocyte receptor, the virus simply enters the cell adsorbed, leading to the parenchymal diffusion phase. All this happens during the incubation period of the disease. Having multiplied in stellate cells, the virus enters the blood through the sinusoids and the phase of secondary generalization of the infection begins, when the virus enters the blood again. The liver already has a memory of the virus, primary sensitization occurs, and the phase of persistent generalization of the infection sets in, and the disease itself sets in - the temperature rises. The liver adsorbs viruses, and a syndrome of cytolysis and cholestasis is manifested. With the loss of function, the main sign will be intoxication, that is, in patients with pronounced intoxication manifestations, which are associated with the release of bile acids, bilirubin into the blood, phenols that disrupt tissue respiration and energy production, damage to the central nervous system (gradually progressive encephalopathy phenomena). Low molecular weight fats, phenols, PVC also cause an effect on the central nervous system. The highest manifestation of encephalopathy is hepatic coma.