Hepatitis C

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

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Epidemiology

Hepatitis C ranks first in the list of factors that provoke chronic liver diseases, ahead of hepatitis B, alcohol and even AIDS. The hepatitis C virus was isolated and identified more than 20 years ago and is classified in the flavivirus group (yellow - from the Latin flavus).

The prevalence of HCV (hepatitis C) today reaches from 1.5 to 2% in all countries considered developed, according to experts, there are up to 200 million people infected with the virus worldwide, and their number is growing annually. Regional features that the epidemiology of hepatitis C has are obviously related to the standard of living of the population and the quality of sanitary and epidemiological surveillance. In general, the statistics are as follows:

1. The countries of the Middle East, where Egypt sadly holds the palm of primacy – up to 20% of the population.
2. Countries with a high standard of living – Western Europe, the USA, Japan and Australia – 1.5-2%.
3. The Northern European countries – Norway, Denmark, Sweden, Finland, Greenland, Iceland – only 0.1-0.8%.
4. Eastern European countries, as well as North Africa and Asia – from 5 to 6.5%.

It is obvious that the dynamics of the growth of hepatitis C cases, the year-on-year increase in the rates of detected chronic HCV and the growth of drug addiction indicate that the real number of infected people is much higher. Today, many doctors are speaking with concern about the hidden HCV epidemic.

The incidence of this disease in Ukraine in 2010 compared to 1994 (the first year of official registration) increased almost 7 times: from 3.2 to 20.7 per 100 thousand population. Since 2001, the incidence of acute hepatitis C began to decrease, and in 2006 this figure was 4.5 per 100 thousand population. It should be taken into account that the official registration data are probably incomplete, 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 patients are people aged 20-29 years and adolescents. In Ukraine, a sharp increase in the incidence of acute viral hepatitis observed in 1996-1999 has been replaced by an epidemic of chronic viral hepatitis. In the structure of chronic liver lesions, the share of viral hepatitis C reaches more than 40%.

How can you get hepatitis C?

Viral hepatitis C is an anthroponosis: the only source (reservoir) of the infectious agent is 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 (vertically - when the virus is transmitted from mother to child, contact - when using household items and during sexual intercourse) and artificially (artificially). An artificial route of infection can be realized 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 viral hepatitis C are less common than with viral hepatitis B, which is probably due to the lower concentration of HCV in biological substrates. The risk of infection of a child by a seropositive mother is on average 2%, increases to 7% if HCV RNA is detected in the blood of a pregnant woman, up to 10% if the woman practices intravenous drug use, and up to 20% if a pregnant woman is registered as coinfected with HCV and HIV. Infected mothers are not contraindicated in breastfeeding, however, in the presence of cracks in the nipples, according to some researchers, breastfeeding should be avoided. Infection is rarely transmitted from child to child, therefore, the child's attendance at school and his communication with other children, including playing contact sports, are not limited. There is no need to limit household contacts, except for those that may involve contact with infected blood (sharing a toothbrush, razor, manicure accessories, etc.).

Infection of regular sexual partners who are HCV carriers rarely occurs through sexual contact. Therefore, when recommending that HCV carriers inform their sexual partners about the infection, it should be emphasized that the risk of transmission during sexual contact is so low that some experts consider the use of condoms unnecessary. 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 drugs without observing the rules of safe injection practice. Most newly registered patients with acute hepatitis C (70-85%) have indications of intravenous drug use. The rise in the incidence of viral hepatitis C in Ukraine in the 90s is due to the growth of drug addiction. According to experts, there are more than 3 million people in Ukraine who consume narcotic and psychotropic substances, among them in recent years the number of anti-HCV positive has increased 3-4 times, therefore this category of people is particularly dangerous as a source of viral hepatitis C. The risk group also includes patients undergoing hemodialysis, patients with oncological and hematological pathology and others receiving long-term and repeated inpatient treatment, as well as health workers who have contact with blood, and donors. It is also possible to become infected with HCV through transfusion of infected blood products, although in recent years, due to the mandatory determination of anti-HCV in donors, the number of people 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 exclude the possibility of transmitting this infection, therefore, in recent years, a method of quarantining blood products has been introduced into the transfusion service. In some countries, donor blood is tested for the presence of HCV RNA using the PCR method. The pathogen can be transmitted not only during parenteral medical procedures (injections, dental and gynecological procedures, gastro-, colonoscopy, etc.), but also during tattooing, ritual incisions, piercing, manicure, pedicure, etc. in the case of using instruments contaminated with infected blood.

The natural susceptibility of people to HCV is high. The probability of infection is largely determined by the infectious dose. The 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 repeated infection with HCV by both a different and a homologous strain has been shown).

About 3% of the world's population (170 million people) is infected with HCV, and approximately 80% of people who have had the 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.

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Causes hepatitis C

The cause of hepatitis C is the hepatitis C virus (HCV). It belongs to the Flaviviridae family, has a lipid membrane, a spherical shape, an average diameter of 50 nm, the nucleocapsid contains single-stranded linear RNA. The genome contains about 9600 nucleotides. In the HCV genome, two regions are distinguished, one of which (the core locus, El and E2/NS1) encodes structural proteins that are part of the virion (nucleocapsid, membrane proteins), the other (the NS2 locus, 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). Studying the functional role of proteins encoded in the non-structural region of the HCV genome and involved in viral replication is of utmost importance for the creation of new drugs that could block viral replication.

It has been established that the hepatitis C virus circulates in the human body as a mixture of mutant strains that are genetically distinct from each other and are called "quasispecies". The peculiarity of the HCV genome structure is its high mutational variability, the ability to constantly change its antigen structure, which allows the virus to avoid immune elimination and persist in the human body for a long time. According to the most common classification, there are six genotypes and over a hundred subtypes of HCV. Different genotypes of the virus circulate in different regions of the Earth. Thus, in Ukraine, genotypes 1b and 3a are predominantly common. The genotype does not affect the outcome of the infection, but it allows predicting 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.

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Risk factors

The following risk groups are distinguished, which are also a source of infection for others. These are people suffering from drug addiction. Statistics provide information on the following percentages of infection:

• Hemotransfusion (blood transfusion) and organ transplantation – more than 55%.
• Injection drug use – 20-22%.
• Hemodialysis (extrarenal blood purification) – 10-12%.
• Sexual contacts – 5-7%.
• Professional route of infection (doctors, medical workers who have contact with blood – 5-6%.

High-risk groups are all people associated with injection drugs, in addition, the following fall into the risk category of infection:

• Patients who, for vital indications, require systematic blood transfusion procedures.
• Patients undergoing hemodialysis.
• Patients of oncology clinics with tumors of the hematopoietic organs.
• Medical personnel in contact with blood.
• Donors, including individuals who donate plasma.
• People who do not use protection during sexual intercourse and have multiple partners.
• HIV-infected.
• Persons with non-traditional sexual orientation (homosexuality).
• Sexual partners of people with hepatitis.
• Pregnant women infected with HCV virus, in terms of transmission of hepatitis to the fetus.

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Pathogenesis

After infection, HCV enters hepatocytes hematogenously, where its replication occurs predominantly. Liver cell damage is caused by the direct cytopathic effect of virus components or virus-specific products on cell membranes and hepatocyte structures and immunologically mediated (including autoimmune) damage directed at intracellular HCV antigens. The course and outcome of HCV infection (virus elimination or persistence) is determined primarily by the effectiveness of the immune response of the macroorganism. In the acute phase of infection, the HCV RNA level reaches high concentrations in the blood serum during the first week after infection. In acute hepatitis C (both in humans and in experiments), the specific cellular immune response is delayed by at least one month, the humoral response by two months, the virus "outpaces" the adaptive immune response. The development of jaundice (a consequence of T-cell liver damage) is rarely observed in acute hepatitis C. Approximately 8-12 weeks after infection, when the maximum increase in the ALT level in the blood occurs, a decrease in the HCV RNA titer occurs. 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 chronic hepatitis C 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 ceases to be 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 a return of viremia is detected 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. Almost all patients who spontaneously recover from acute hepatitis C have a strong polyclonal specific T-cell response, which convincingly demonstrates 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. Viral and host factors that determine the inability of the immune response to control HCV infection have not been adequately studied. The phenomenon of escape from control of the host immune response is known, which is due to the high mutational variability of the HCV genome. As a result, the virus is able to persist in the human body for a long time (possibly for life).

With HCV infection, the appearance of various extrahepatic lesions is possible, caused by immunopathological reactions of immunocompetent cells, which are realized either by immune cellular (granulomatosis, lymphomacrophage infiltrates) or immune complex reactions (vasculitis of various localizations).

Morphological changes in the liver in viral hepatitis C are nonspecific. They mainly include lymphoid infiltration of portal tracts with the formation of lymphoid follicles, lymphoid infiltration of lobules, step necrosis, steatosis, damage to 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: lymphocytes predominate in portal tracts and around the foci of damage and death of hepatocytes, which reflects the participation of the immune system in the pathogenesis of liver damage. Fatty dystrophy is observed in hepatocytes, while liver steatosis is more pronounced in genotype 3a infection than in genotype 1. Chronic hepatitis C, even with a low degree of histological activity, can be accompanied by the development of liver fibrosis. Not only portal and periportal zones of lobules are subject to fibrosis, perivenular fibrosis is also often detected. Severe fibrosis leads to the development of cirrhosis (diffuse fibrosis with the formation of false lobules), against which hepatocellular carcinoma may develop. Liver cirrhosis develops in 15-20% of patients with pronounced inflammatory changes in liver tissue. Currently, in addition to the morphological description of the obtained biopsy samples, several numerical assessment systems have been developed that allow for a semi-quantitative (rank) determination of IGA - the activity of the inflammatory-necrotic process in the liver, as well as the stage of the disease, determined by the degree of fibrosis (fibrosis index). Based on these indicators, the prognosis of the disease, strategy and tactics of antiviral therapy are determined.

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Symptoms hepatitis C

Clinical symptoms of hepatitis C do not differ fundamentally from those of other parenteral hepatitis. The duration of the pre-icteric period ranges from several days to 2 weeks. It may be absent in 20% of patients.

Infection with the hepatitis C virus leads to the development of acute hepatitis C, which in 80% of cases occurs in 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 (on average 6-8 weeks).

Symptoms of acute hepatitis C

In the pre-icteric period, asthenovegetative syndrome most often prevails, expressed by weakness and rapid fatigue. Dyspeptic disorders often occur: decreased appetite, discomfort in the right hypochondrium, nausea and vomiting. Arthralgic syndrome is much less common, skin itching is possible. The icteric period proceeds much easier than with other parenteral hepatitis. The leading symptoms of the acute period are weakness, decreased appetite and a feeling of discomfort in the abdomen. Nausea and itching occur in a third of patients, dizziness and headache - in every fifth patient, vomiting - in every tenth patient. Almost all patients have an enlarged liver, 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 bilirubin level (in the anicteric form, the amount of bilirubin corresponds to normal values), a significant increase in ALT activity (more than 10 times). Frequently, a wave-like nature of hyperfermentemia is noted, which is not accompanied by a deterioration in well-being. In most cases, the bilirubin level is normalized by the thirtieth day after the appearance of jaundice. Other biochemical indicators (sedimentary tests, the level of total protein and protein fractions, prothrombin, cholesterol, alkaline phosphatase) are usually within normal values. Sometimes an increase in the GGT content is recorded. In the hemogram, there is a tendency towards 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. A severe course of the disease is possible (rare), and fulminant acute hepatitis C, leading to a fatal outcome, is very rare. In the natural course of viral hepatitis C, 20-25% of patients with acute hepatitis C spontaneously recover, while the remaining 75-80% develop chronic hepatitis C. Definitive criteria for recovery after acute hepatitis C have not been developed, but spontaneous recovery can be considered if a patient who has not received specific antiviral therapy, feels well, and has normal liver and spleen sizes, has normal blood biochemical parameters, and HCV RNA is not detected in the blood serum for at least two years after acute hepatitis C. Factors associated with spontaneous elimination of the virus include young age, female gender, and a certain combination of genes of the major histocompatibility complex.

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Symptoms of Chronic Hepatitis C

In 70-80% of people who have had the acute form of the disease, chronic hepatitis develops, which is the most common pathology among chronic viral liver diseases. The development of chronic hepatitis C may be accompanied by normalization of clinical and biochemical parameters after the acute period, however, hyperenzymemia and HCV RNA in the blood serum subsequently 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 still unknown. In 30% of patients with chronic hepatitis C, the disease has a progressive course, in some of them (12.5% - over 20 years, 20-30% - over 30 years) cirrhosis of the liver develops, which can cause 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 failure, 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, 5-year survival of patients with this form of cancer is less than 5%. Independent risk factors for fibrosis progression: male gender, age at infection (progression occurs faster in patients infected at the age of over 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 more rapid formation of fibrosis. The likelihood of disease progression is not associated with the HCV genotype or viral load.

A characteristic feature of chronic hepatitis C is its latent or low-symptom course for many years, usually without jaundice. Increased ALT and AST activity, 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 detected by chance, during examination before surgery, during medical examination, etc. Sometimes patients come to the doctor's attention only when liver cirrhosis develops and signs of its decompensation appear.

Chronic НСV infection may be accompanied by normal ALT activity in repeated studies for 6-12 months, despite ongoing HCV RNA replication. The proportion of such patients among all patients with chronic infection is 20-40%. In some of these patients (15-20%), liver biopsy can reveal serious fibrotic changes. Puncture liver biopsy is an important diagnostic method that allows identifying patients with progressive serious liver damage who require urgent antiviral therapy. The rate of progression of liver fibrosis in patients with normal ALT activity is apparently lower than in patients with increased activity.

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

Symptoms of hepatitis C without icterus

The disease begins gradually, complaints of fatigue, loss of appetite, mild abdominal pain may be noted. After a few days, an enlargement and thickening of the liver, which protrudes 2-5 cm below the costal arch, is noted in the foyer of developed asthenic and dyspeptic phenomena; in some patients, an enlargement of the spleen is simultaneously observed.

Frequency of clinical symptoms (%) during the peak period of hepatitis C

Symptom	Form
	Anicteric	Easy	Medium-heavy
Headache	-	6.0	14.0
Weakness	6.9	18	47.0
Anxiety	-	-	4.7
Decreased appetite	13.8	39.0	56.4
Vomit	-	15.0	23.5
Stomach ache	6.9	12.0	56.4
Enlarged liver (from the hypochondrium): up to 2 cm	72.4	78.0	51.7
From 2.5 to 5 cm	27.6	18.0	42.3
Liver sensitivity	17.2	63.0	47.0
Liver consistency: dense elastic	48.3	66.0	61.1
Compacted	24.1	24.0	37.6
Enlargement of the spleen (from the hypochondrium): up to 1 cm	17.2	18.0	32.9
Up to 3 cm	-	3.0	14.0

Among the liver function test indicators, hyperfermentemia (3-10-fold increase in aminotransferase activity) with a normal bilirubin level is noteworthy. Sediment tests are slightly changed.

Biochemical parameters during the peak of acute hepatitis C

Indicator	Form
	Anicteric	Easy	Medium-heavy
Bilirubin: total, µmol/l bound, µmol/l	13.1±0.4 6.2±0.3	40.3+4.9 27.0±3.2	119.0±12.3 87.4±5.3
ALT, U/L	290±35	330±28	400±41
ACT, U/L	160±45	250±30	320±53
Thymol test, U/l	6.3±1.1	7.8±1.6	12.0±2.4

Mild form

The disease begins with weakness, loss of appetite, and sometimes abdominal pain. Body temperature remains normal or does not rise above 38 °C. After a few days, an enlarged liver is detected.

The pre-icteric period lasts from 3 to 7 days, on average 4.3±1.2 days. With the onset of jaundice, the condition of patients does not worsen, intoxication does not increase. In the icteric period, moderate hepatosplenic syndrome is determined. The liver is compacted, sensitive, protrudes from the hypochondrium by 1-3 cm; the spleen is palpable in most patients at the edge of the costal margin and in some - 1-3 cm below the costal margin.

In the blood serum, the bilirubin content is on average 40.3±5.0 μmol/l, almost exclusively due to the conjugated fraction, the activity of liver cell enzymes increases by no more than 3-10 times. The thymol test values are within normal limits or slightly elevated.

The duration of the icteric period is from 5 to 12 days, on average 7.8±T.2 days.

Moderate form

In the initial period of the disease, asthenic and dyspeptic symptoms are characteristic (lethargy, adynamia, dizziness, loss of appetite, repeated vomiting, abdominal pain), in some patients an increase in body temperature to 38-39 C is possible. The pre-icteric period lasts 5-8 days, averaging 5.7±1.7 days.

With the appearance of jaundice, the symptoms of intoxication persist or intensify, but in general they are expressed moderately. Within 2-5 days, jaundice reaches its maximum, then within 5-10 days, and sometimes longer, it remains at the same level and then begins to decrease. On average, the duration of the icteric period is 16±3.5 days. During the icteric period, the edge of the liver is palpated below the costal arch by 2-5 cm, and the organ is determined to be compacted and painful. The spleen is usually palpated 1-3 cm below the costal arch. Some patients have isolated "bruises" on the limbs and trunk as a manifestation of hemorrhagic syndrome.

A biochemical blood test shows a 5-10-fold increase in bilirubin levels, an average of 119.0+12.3 μmol/l, mainly conjugated, high activity of hepatocellular enzymes, while ALT and AST levels exceed the norm by 5-15 times, thymol test levels are moderately elevated, and prothrombin index levels are reduced to 60-65%.

On average, the duration of the icteric period is 16.0±3.5 days.

Severe form

It is rare with hepatitis C. In the initial period of the disease, severe weakness, fatigue, dizziness, headaches, anorexia, pain in the right hypochondrium, nausea, and repeated vomiting are observed. In the icteric period, intoxication is pronounced, and manifestations of hemorrhagic syndrome are observed (ecchymosis on the limbs and trunk, petechial elements, nosebleeds). The liver is dense, painful, and is determined 5-10 cm below the costal arch; the spleen protrudes from the hypochondrium by 3-5 cm.

In the blood serum, the bilirubin level increases more than 10 times, due to both the conjugated and unconjugated fractions; high hyperfermentemia and a decrease in the prothrombin index to 50% or more are characteristic.

The icteric period lasts up to 3-4 weeks and, as a rule, is accompanied by prolonged intoxication.

Malignant form

There are only isolated reports in the literature on the development of malignant (fulminant) hepatitis C in both adults and children. It is reported that the clinical manifestations of fulminant hepatitis C are no different from those of HBV infection.

Subclinical hepatitis C

Characterized by the absence of clinical manifestations, the presence of biochemical and serological changes. In the blood serum, the activity of aminotransferases increases and specific markers appear - HCV RNA and anti-HCV.

Stages

A distinction is made between acute, protracted and chronic courses of the disease.

Acute course of hepatitis C is characterized by a relatively rapid reverse change in clinical and laboratory parameters of hepatitis with recovery and complete restoration of the functional state of the liver within 3 months from the onset of the disease.

Benign disease variants may include:

• recovery with complete structural and functional restoration of the liver;
• recovery with residual liver fibrosis (residual fibrosis);
• recovery from biliary tract lesions (dyskinesia, cholecystitis, cholangitis, etc.).

Prolonged course of hepatitis C is often manifested by the fact that after the disappearance of jaundice and, it would seem, the end of the acute period, hyperfermentemia is prolonged. The condition of patients in these cases is quite satisfactory, the liver is moderately enlarged, but the spleen often ceases to be palpated. Hyperfermentemia can persist for 6-9 and even 12 months, but eventually normalization of enzyme activity and complete recovery occur.

Chronic hepatitis C is established after the active process in the liver has been established for more than 6 months. Most clinicians indicate a high frequency of chronic hepatitis C - from 40 to 56-81%. Moreover, one of the frequent variants is considered to be asymptomatic hyperfermentemia from the very beginning of the disease, which persists for several years, sometimes increasing, sometimes weakening.

According to the research data, 42 children (53.4%) had elevated aminotransferase activity after the acute period had subsided, and 10 children continued to have НСV RNA in their blood serum; at the same time, dense enlarged liver was palpated in almost all patients. Chronic process developed approximately equally from all forms of acute hepatitis C. It should be noted that all children, both those who recovered and those with the outcome of the disease in the chronic form, had antibodies to the hepatitis C virus in their blood serum.

Apparently, it is possible to state as a natural phenomenon the fact of transition of acute manifest hepatitis C to chronic form. There is no strict substantiation of this fact yet, but understanding of the indicated regularity will be obtained by studying НСV-infection taking into account genotypes of RNA of hepatitis C virus.

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Forms

• By the presence of jaundice in the acute phase of the disease:
  • Icteric.
  • Anicteric.
• By duration of the course.
  • Acute (up to 3 months).
  • Prolonged (more than 3 months).
  • Chronic (more than 6 months).
• By severity.
  • Light.
  • Medium-heavy.
  • Heavy.
  • Fulminant.
• Complications.
  • Hepatic coma.
• Outcomes.
  • Recovery.
  • Chronic hepatitis C.
  • Cirrhosis.
  • Hepatocellular carcinoma.

According to the nature of the clinical manifestations of the acute phase of the disease, a distinction is made between typical and atypical hepatitis C. Typical cases include all cases of the disease accompanied by clinically visible jaundice, while atypical cases include anicteric and subclinical forms.

All typical variants of the disease, depending on the severity of symptoms (intoxication, jaundice, hepatosplenomegaly, etc.) and biochemical changes (increased bilirubin levels, decreased prothrombin index, etc.), are usually divided into mild, moderate, severe and malignant (fulminant) forms.

Depending on the duration, a distinction is made between acute, protracted and chronic hepatitis C.

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Diagnostics hepatitis C

Clinical symptoms of acute hepatitis C are mild in a significant proportion of patients, so the diagnosis of acute hepatitis C is based on a comprehensive assessment of epidemiological history data during the periods corresponding to the incubation period, jaundice, increased bilirubin levels, an increase in ALT levels by more than 10 times, the presence of newly identified markers of viral hepatitis C (anti-HCV, HCV RNA) while excluding hepatitis of other origins. Considering that most patients with acute hepatitis C do not have clinical signs of acute hepatitis, and the available serological and biochemical manifestations do not always allow distinguishing acute hepatitis from an exacerbation of chronic hepatitis, the diagnosis of acute hepatitis C is established in cases where, along with characteristic clinical, epidemiological and biochemical data, antibodies to HCV are absent in the initial study of blood serum, which appear 4-6 weeks or more after the onset of the disease. To diagnose acute hepatitis C, one can resort to detecting viral RNA using PCR, since it can be detected already in the first 1-2 weeks of the disease, while antibodies appear only after several weeks. The use of third-generation test systems, which are much more sensitive and specific, allows detecting anti-HCV in the blood serum already 7-10 days after 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, 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 the remission phase after the elimination of HCV RNA as a result of antiviral therapy. Modern test systems allow to increase the detection rate of anti-HCV in 98-100% of immunocompetent infected individuals, while in immunocompromised patients the detection rate of anti-HCV is significantly 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, autoimmune diseases and immunodeficiencies, etc.).

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

Standard for the diagnosis of acute hepatitis C

Mandatory laboratory tests:

• clinical blood test;
• biochemical blood test: bilirubin, ALT, AST, thymol test, prothrombin index;
• immunological study: anti-HCV, HB-Ag. anti-HBc IgM, anti-HIV;
• determination of blood type, Rh factor;
• clinical urine analysis and bile pigments (bilirubin).

Additional laboratory tests:

• immunological study: HCV RNA (qualitative analysis), total antidelta, anti-HAV IgM, anti-HEV IgM, CIC, 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 balance of the blood;
• coagulogram.

Instrumental studies:

• Ultrasound of abdominal organs;
• ECG;
• chest x-ray.

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Standard for the diagnosis of chronic hepatitis C

Mandatory laboratory tests:

• clinical blood test;
• biochemical blood test: bilirubin, ALT, AST, thymol test;
• immunological study: Anti-HCV; HBcAg;
• clinical urine analysis 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 type, Rh factor;
• immunological study: HCV RNA (qualitative analysis), total antidelta, anti-HAV IgM, anti-HEV IgM, CIC, LE cells, anti-HBc IgM, anti-delta IgM, HBeAg, anti-HBe, HBV DNA (qualitative analysis), autoantibodies, anti-HIV, a-fetoprotein;
• stool for occult blood.

Instrumental diagnostics (additional):

• Ultrasound of abdominal organs:
• ECG;
• chest x-ray:
• Percutaneous liver biopsy:
• EGDS.

Differential diagnosis

Differential diagnostics are carried out with other viral hepatitis. When making a diagnosis, the relatively mild course of the disease, characteristic of acute hepatitis C, with a significantly lower degree of intoxication syndrome, with rapid normalization of biochemical parameters, is taken into account. The dynamics of viral hepatitis markers is of great importance when conducting differential diagnostics.

Indications for consultation with other specialists

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

Treatment hepatitis C

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

Drug treatment of hepatitis C

Standard interferon alpha-2 is used as an etiotropic agent in the treatment of acute hepatitis C. The number of people recovering from acute hepatitis C can be increased (up to 80-90%) by 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 alpha-2 10 million IU intramuscularly daily until transaminase levels are normalized (which usually occurs within 3-6 weeks from the start of drug use).

Monotherapy with pegylated interferon alpha-2 for 24 weeks is effective.

The complex of therapeutic measures for chronic hepatitis C includes basic and etiotropic (antiviral) therapy. Basic therapy involves following a diet (table No. 5), taking a course of drugs that normalize the gastrointestinal tract, affecting the functional activity of hepatocytes (pancreatic enzymes, hepatoprotectors, choleretic agents to restore intestinal microflora, etc.). It is also necessary to limit physical activity, provide patients with psychoemotional and social support, and treat concomitant diseases. The goal of etiotropic therapy for 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 development of cirrhosis of the liver and primary hepatocellular carcinoma, as well as improving the quality of life associated with health.

Currently, the best option for antiviral therapy of chronic hepatitis C is the combined use of pegylated interferon alpha-2 and ribavirin for 6-12 months (depending on the genotype of the virus that caused the disease). The standard treatment for chronic hepatitis C is standard interferon alpha-2, a combination of standard interferon alpha-2 and ribavirin. as well as a combination of pegylated interferon alpha-2 and ribavirin. Standard interferon alpha-2 is prescribed at a dose of 3 million IU 3 times a week subcutaneously or intramuscularly. pegylated interferon alpha-2a is prescribed at a dose of 180 mcg, pegylated interferon alpha-2b - at the rate of 1.5 mcg / kg - 1 time per week subcutaneously for 48 weeks for genotype 1 and 4 for 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.

It is fundamentally important to establish indications for etiotropic therapy of chronic genotype C and to select an adequate program for its implementation. In each case, a careful differentiated approach is necessary when determining the group of people subject to treatment. According to the recommendations of the consensus conferences held in 2002, antiviral treatment of hepatitis C is carried out only in adult patients with chronic hepatitis C, in the presence of HCV RNA in the blood serum and in the presence of histological signs of liver damage.

Treatment may not be prescribed to patients with mild chronic hepatitis C, for whom the probability of disease progression in the absence of aggravating factors (obesity, excessive alcohol consumption, HIV co-infection) is low. In these situations, dynamic monitoring of the course of the disease is possible.

Treatment is prescribed to 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 to patients with liver cirrhosis (in order to obtain a virological response, stabilize the process in the liver, prevent hepatocellular carcinoma). After the primary course of treatment, in the absence of a virological response, but in the presence of a biochemical response, maintenance therapy with interferon alpha-2 can be prescribed to slow the progression of the disease. Predictors of response to treatment in chronic hepatitis C are host factors and viral factors. Thus, patients under 40 years of age, patients with a short duration of the disease and female patients more often respond to interferon therapy. The disease is less treatable in patients who abuse alcohol, have diabetes mellitus, liver steatosis, and obesity. Therefore, diet modification before treatment can improve its results. The response rate to treatment is higher in patients with mild fibrosis than in stage 3-4 fibrosis or cirrhosis. However, half of patients with cirrhosis achieve a virological response (37% with genotype 1, more than 70% with genotype 1), so this category of patients should also receive antiviral therapy, although its tactics should be adjusted if necessary. The frequency of successful virological response during treatment with standard and pegylated interferon alpha-2 with or without ribavirin depends on the HCV genotype and viral load. Most often, patients with genotypes 2 and 3 respond to hepatitis C treatment, while the probability of a successful virological response is significantly lower in patients with genotypes 1 and 4. Patients with a high viral load (>850 thousand IU/ml) respond worse to treatment than patients with a low viral load. The patient's adherence to treatment is of great importance in achieving the effect of antiviral treatment. The probability of achieving the effect is higher if the patient has received the full course of treatment - more than 80% of the drug dose for more than 80% of the intended treatment period.

The effectiveness of specific treatment for hepatitis C is assessed based on several criteria: virological (disappearance of HCV RNA from the blood serum), biochemical (normalization of ALT levels), and morphological (reduction in the histological activity index and fibrosis stage). There may be several possible responses to antiviral treatment for hepatitis C. If normalization of ALT and AST levels and disappearance of HCV RNA in the blood serum are recorded immediately after the end of therapy, then this is called complete remission, and a biochemical and virological response is observed at the end of treatment. A stable biochemical and virological response is observed if normal ALT levels are detected in the blood serum 24 weeks (6 months) after the end of treatment and HCV RNA is absent. A relapse of the disease is recorded when the ALT and AST levels increase and/or HCV RNA appears in the blood serum after the end of treatment. The absence of a therapeutic effect means the absence of normalization of ALT and AST levels and/or the persistence of HCV RNA in the blood serum during the treatment. Prediction of the effectiveness of 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 the viral load by more than 2xIg10 in the blood serum after 12 weeks of treatment. When registering an early virological response, the probability of effective antiviral therapy is high, while its absence indicates low chances of achieving a successful virological response even if the patient's treatment course is 48 weeks. Currently, when predicting the effectiveness of antiviral therapy, they focus on a rapid virological response - the disappearance of HCV RNA 4 weeks after the start of antiviral treatment.

The duration of hepatitis C treatment depends on the HCV genotype. For genotype 1, if HCV RNA is absent in the blood serum after 12 weeks of treatment, the duration of treatment is 48 weeks. If the viral load of a patient with genotype 1 decreases by at least 2xlgl0 compared to the initial level after 12 weeks of treatment, but HCV RNA continues to be detected in the blood, a repeat HCV RNA test should be performed on the 24th week of treatment.

If HCV RNA remains positive after 24 weeks, hepatitis C treatment should be discontinued. The absence of an early virological response allows for a fairly accurate prediction of the ineffectiveness of further therapy, and therefore treatment should also be discontinued. With genotypes 2 and 3, combination therapy with interferon and ribavirin is administered for 24 weeks without determining the viral load. With genotype 4, as with genotype 1, combination therapy for hepatitis C is recommended for 48 weeks. Adverse events are possible during treatment with interferon drugs and ribavirin. A mandatory condition for ribavirin therapy is the use of contraception by both partners throughout the entire treatment period (it is also recommended to avoid pregnancy for another 6 months after the end of the treatment course). Side effects of interferon and ribavirin sometimes require a reduction in their doses (temporarily or permanently) or discontinuation of the drugs. During treatment of hepatitis C, patients should be monitored, biochemical monitoring should be performed (every two weeks at the beginning of treatment, then monthly), virological monitoring (for genotype 1 - 12 weeks from the beginning 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. A hemogram is examined, once every four months - the concentration of creatinine and uric acid, TSH, ANF.

Due to the presence of common transmission routes of viruses, chronic hepatitis C is often accompanied by infection with HBV and/or HIV. Coinfection increases the risk of liver cirrhosis, terminal liver cell failure and hepatocellular carcinoma, as well as mortality in patients compared with that in patients with HCV monoinfection. Preliminary data indicate that the combination of pegylated interferon and ribavirin allows achieving a virological and/or histological response in HIV-infected patients with chronic hepatitis C. When prescribing antiviral therapy to patients with chronic viral hepatitis in mixed infection, the choice of treatment regimen is determined by the presence of the replication phase of HBV 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 copious 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.

Clinical examination

A special feature of the medical examination of patients with viral hepatitis C is the duration of the procedure. Patients with viral hepatitis C are observed for life due to the lack of reliable criteria for recovery in order to promptly identify signs of reactivation of the infection and correct the tactics of observation and treatment.

[ 41 ], [ 42 ]

What does a patient with viral hepatitis C need to know?

You have had acute hepatitis C, and you need to know that the disappearance of jaundice, satisfactory laboratory parameters and good health are not indicators of complete recovery, since complete restoration of liver health occurs within 6 months. To prevent exacerbation of the disease and transition to a chronic form, it is important to strictly follow the doctor's recommendations related to subsequent observation and examination in a clinic, daily routine, diet, and working conditions.

Diet and regimen for hepatitis C

Semi-bed rest regimen for mild and moderate acute hepatitis C. Strict bed rest regimen for severe acute hepatitis C. For chronic hepatitis C - compliance with the work and rest regimen, night shift work and work in industries associated with toxic products, business trips, lifting weights, etc. are not recommended.

A gentle diet (in terms of cooking and exclusion of irritants), table No. 5.

Return to work activities involving high physical stress or occupational hazards is permitted no earlier than 3-6 months after discharge. Until then, work may be continued in a light work mode.

After discharge from the hospital, you should be careful of hypothermia and avoid overheating in the sun, trips to southern resorts are not recommended for the first 3 months. You should also be careful of taking medications that have a side (toxic) effect on the liver. After normalization of biochemical blood parameters, participation in sports competitions is prohibited for 6 months. Those who have had acute hepatitis B are exempt from preventive vaccinations for 6 months. Sports activities are limited only to a set 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 beverages (including beer) are strictly prohibited. It is necessary to eat regularly during the day every 3-4 hours, avoiding overeating.

Allowed:

• milk and dairy products in all forms;
• boiled and stewed meat - beef, veal, chicken, 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 and milk soups;

You should limit your consumption 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 omelets);
• cheese (in small quantities, but not spicy);
• meat products (beef sausages, doctor's sausages, dietary sausages, table sausages);
• salmon and sturgeon caviar, herring:
• tomatoes.

Prohibited:

• alcoholic drinks:
• all types of fried, smoked and pickled products;
• pork, lamb, goose, duck;
• hot spices (horseradish, pepper, mustard, vinegar);
• confectionery (cakes, pastries);
• chocolate, chocolate candies, 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. Removal from the register in case of a favorable outcome is carried out no earlier than 12 months after discharge from the hospital.

Remember that only observation by an infectious disease specialist and regular laboratory testing 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 for hepatitis C, you must strictly follow the regimen for administering the drug and regularly come for laboratory monitoring of blood counts, as this will minimize the likelihood of side effects of the drug and ensure control over the infection.

You must show up for a laboratory examination on the day strictly prescribed by your doctor, on an empty stomach.

Your first visit to the KIZ polyclinic is scheduled by your attending physician.

The established control periods for follow-up medical examinations at the clinic or hepatology center are mandatory for all those who have had viral hepatitis C. If necessary, you can contact the hospital follow-up office, or the hepatology center, or the KIZ of the clinic also in addition to these periods.

Be attentive to your health!

Strictly follow the regime and diet!

Visit your doctor regularly for check-ups!

Prevention

Prevention of hepatitis C is particularly important due to the epidemiological prevalence of the disease and the lack of a vaccine against this deadly infection.

The non-specific method is the widespread use of disposable medical instruments used to perform procedures involving blood. In addition, blood transfusions and hemodialysis are prescribed only for strict indications, when the risk of mortality exceeds the risk of hepatitis C infection. All medical personnel are regularly equipped with disposable gloves, special means for processing devices and reusable instruments.

Specific prevention of hepatitis C is strict control of donor blood and identification of possible virus carriers. In many developed countries, these measures are enshrined in official documents of health authorities. All blood products are processed by heating or chemical neutralization to prevent HCV transmission. Vaccination of hepatitis C carriers with hepatitis A and B vaccines is also considered effective.

Prevention of hepatitis C involves a comprehensive examination of people in risk groups for possible carriage of the virus:

• Persons registered for injection drug use.
• HIV-infected patients.
• Patients diagnosed with hemophilia.
• Patients undergoing hemodialysis.
• Patients who underwent organ transplantation – before 1992.
• Patients who received a blood transfusion before 1992.
• Infants whose mothers are infected with HCV.
• Medical personnel in contact with blood.

It is also advisable to conduct an examination to detect the hepatitis C virus in individuals with a history of STDs (sexually transmitted diseases).

Hepatitis C Vaccination

Unfortunately, there is currently no vaccine to prevent HCV infection. Vaccination against hepatitis C is the goal of many hundreds of scientists, doctors, microbiologists, and infectious disease specialists who are working hard to create a highly effective antiviral drug, a serum aimed at interrupting the mutation of specific subtypes, nucleotide links that damage hepatocytes. The goal of vaccine developers is to identify and detect a single protein that would be specific to all multiple subtypes of hepatitis C. Once this happens, the immune system will be able to produce neutralizing or protective antibodies. Vaccination against hepatitis C would help slow down the increasing rate of HCV prevalence, and ideally stop the epidemic of the disease. According to WHO, experimental vaccine samples are being tested on animals in laboratories in European countries (France, Denmark), but there is no clinical confirmation of the effectiveness of these drugs yet.

[ 43 ], [ 44 ], [ 45 ]

Forecast

The statistical data that is systematically collected and analyzed by the WHO is not encouraging. The prognosis for hepatitis C in figures is as follows:

• Active, acute course of the disease – development of liver cirrhosis in 20% of cases, of which more than 5% end in carcinoma.
• 60-80% of all people infected with the hepatitis C virus have a chronic form of the disease.
• 70-75% of all patients have pathological changes in the structure and functions of the liver without malignancy (development of cancer).
• In 20% of patients with chronic HCV, liver cirrhosis develops.
• 30-35% of patients with hepatitis C accompanied by cirrhosis die from liver cancer.
• 5% of patients with chronic hepatitis C die from carcinoma.

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

[ 46 ], [ 47 ], [ 48 ]