Hepatitis C

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

[1], [2]

Epidemiology

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

The prevalence of HCV (hepatitis C) currently stands at between 1.5 and 2% in all countries considered to be developed, according to experts, there are up to 200 million people infected with the virus worldwide and their number increases annually. Regional features that have the epidemiology of hepatitis C, obviously, are 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. Countries in the Middle East, where the sad palm tree is held by Egypt - up to 20% of the population.
2. Countries with a high standard of living - Western Europe, the United States, Japan and Australia - 1.5-2%.
3. Nordic countries - Norway, Denmark, Sweden, Finland, Greenland, Iceland - only 0.1-0.8%.
4. The countries of Eastern Europe, as well as North Africa and Asia - from 5 to 6.5%.

It is obvious that the dynamics of the growth of hepatitis C diseases, increasing indicators of the detected chronic HCV with each goal and the growth of drug addiction, indicate that the real number of infected people is much greater. Today, many doctors with anxiety talk about the hidden epidemic of HCV.

The incidence of this disease in Ukraine in 2010 compared to 1994 (the first year of official registration) increased almost 7-fold: from 3.2 to 20.7 per 100 thousand of the population. Since 2001, the incidence of acute hepatitis C began to decline, and in 2006 this figure was 4.5 per 100 thousand of the population. It should be taken into account that the official registration data is probably not complete, since it is impossible to take into account those cases of acute viral hepatitis that occur without jaundice (in acute hepatitis C, the proportion of such patients is about 80%). The main group of patients are people aged 20-29 and teenagers. In Ukraine, 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%.

How can you get hepatitis C?

Viral hepatitis C - anthroponosis: the only source (reservoir) of the causative agent of infection is a person with acute or chronic hepatitis. Viral hepatitis C refers to infections with a contact (blood-contact) mechanism of transmission of the pathogen, the realization of which occurs naturally (vertical - during transmission of the virus from mother to child, contact - when using household items and during sexual intercourse) and artificial (artificially) ways. The artificial route of infection can be realized through blood transfusion of infected blood or its preparations and any parenteral manipulation (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 frequent than in viral hepatitis B, which is probably due to a lower concentration of HCV in biological substrates. The risk of infection of the child with a seropositive mother averages 2%, increases to 7% when HCV RNA is detected in the pregnant woman's blood, up to 10% if the woman practices intravenous drug use, and up to 20%. If the HCV and HIV are coinfected with the pregnant woman. Infected mothers are not contraindicated with breastfeeding, but in the presence of cracks in the nipples, according to some researchers, from breastfeeding should abstain. From the child to the child, the infection is rarely transmitted, so the school attendance and communication with the child, including contact sports, is not limited. There is no need to limit and household contacts, except for those that can lead to contact with infected blood (using a common toothbrush, razor, manicure accessories, etc.).

Infection with persistent sexual partners of HCV carriers rarely occurs sexually. Therefore, when recommending HCV carriers to be informed of the infection of their sexual partners, it should be emphasized that the risk of transmission during sexual intercourse 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 observing safe injection practices. The majority of newly registered patients with acute hepatitis C (70-85%) have indications for intravenous use of narcotic drugs. The rise in the incidence of viral hepatitis C in Ukraine in the 1990s was due to the increase in drug addiction. According to experts, in Ukraine there are more than 3 million people who consume narcotic and psychotropic substances, among them in recent years the number of anti-HCV positive has increased by 3-4 times, therefore this category of persons poses a particular danger as a source of viral hepatitis C. The risk group also patients who undergo hemodialysis, patients with oncological and hematological pathology and others receiving long-term and multiple in-patient treatment, as well as medical workers who have contact with blood, and donors. It is also possible to infect HCV with transfusion of drugs of infected blood, although in recent years, due to the mandatory determination of anti-HCV in donors, the number of people infected after blood transfusion has dramatically decreased and accounts for 1-2% of all cases of infection. However, even the use of a highly sensitive ELISA for testing donor blood does not completely exclude the possibility of transmission of this infection, so in recent years a method of quarantining blood products has been introduced into the transfusiologic service. In some countries, donor blood testing for the presence of HCV RNA by PCR is performed. The causative agent can be transmitted not only during parenteral medical manipulations (injections, dental and gynecological manipulations, gastro-, colonoscopy, etc.), but also when drawing tattoos, ritual incisions, piercing, manicure, pedicure, etc. In case of using contaminated instruments infected with blood.

The natural susceptibility of people to HCV is high. The probability of infection is determined to a large extent by the infectious dose. The antibodies detected in the organism of the infected person do not possess protective properties, and their detection does not indicate the formation of immunity (the possibility of repeated infection of HCV with other and homologous strains has been shown).

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

[3], [4], [5], [6], [7], [8], [9], [10], [11],

Causes of the hepatitis C

The cause of hepatitis C is the hepatitis C virus (HCV). Relate to the family Flaviviridae, has a lipid envelope, spherical shape, the average diameter is 50 nm, nucleocapsid contains single-stranded linear RNA. The genome contains about 9600 nucleotides. In the HCV genome, two regions are identified, one of which (the core locus , El and E2 / NS1) encodes the structural proteins of 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 which have enzymatic activity and are vital for viral replication (protease, helicase, RNA-dependent RNA polymerase). The study of the functional role of proteins encoded in the non-structural region of the HCV genome and involved in viral replication is of crucial importance for the development of new drugs that could block the replication of the virus.

It has been established that the hepatitis C virus circulates in the human body as a mixture of mutant strains genetically distinguished from each other and termed "quasi-species". The peculiarity of the structure 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 persistently persist in the human body. According to the most common classification, six genotypes and more than a hundred subtypes of HCV are isolated. Different genotypes of the virus circulate in different regions of the Earth. Thus, in Ukraine, genotypes 1b and 3a are prevalent. The genotype does not affect the outcome of the infection, but 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. As an experimental model for studying HCV, only chimpanzees can act.

[12], [13]

Risk factors

The following groups of risk stand out, which are also a source of contamination of others. These are people who are addicted to drugs. Statistics provide information on such percentages of infection: 

• Blood transfusion (transfusion) and organ transplantation - more than 55%.
• Injecting drug use is 20-22%.
• Hemodialysis (extrarenal blood purification) - 10-12%.
• Sexual contacts - 5-7%.
• The professional way of infection (doctors, health workers who have contact with blood - 5-6%.

High-risk groups are all people associated with injecting drugs, in addition to the risk of infection fall: 

• Patients who are vital (vital) indications require systematic procedures for blood transfusion.
• Patients undergoing hemodialysis.
• Patients of oncological dispensaries with tumors of the hemopoiesis.
• Medical personnel who have contact with blood.
• Donors, including those who donate plasma.
• People who do not use protective equipment during sexual intercourse and have several partners.
• HIV-infected.
• Persons with non-traditional sexual orientation (homosexuality).
• Sexual partners of people with hepatitis.
• Pregnant women infected with the HCV virus, in terms of transmission of hepatitis to the fetus.

[14], [15], [16], [17], [18], [19],

Pathogenesis

After infection, HCV hematogenously enters the hepatocytes, where predominantly and occurs its replication. The defeat of the liver cells is due to the direct cytopathic action of the components of the virus or virus-specific products on cell membranes and hepatocyte structures and immunologically mediated (including autoimmune) damage directed to intracellular antigens of HCV. The course and outcome of HCV infection (the elimination of the virus or its persistence) determines primarily the effectiveness of the immune response of the macroorganism. In the acute phase of infection, HCV RNA levels reach high concentrations in the serum during the first week after infection. In acute hepatitis C (both in humans and in experiment), specific cellular immune response lags at least one month, humoral - for two months, the virus "outperforms" the adaptive immune response. The development of jaundice (a consequence of T-cell damage to the liver) is rarely observed in acute hepatitis C. About 8-12 weeks after infection, when there is a maximum increase in ALT level in the blood, the HCV RNA titer decreases. Antibodies to HCV are determined a little later and may be absent altogether, and their appearance does not mean the end of the infection. The majority of 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 part of the patients (about 20%) recover. HCV RNA is no longer detectable when using standard diagnostic tests. Disappearance of the virus from the liver and. Probably from other organs occurs later than from the blood, since the return of viremia is found in some patients and experimental chimpanzees even after 4-5 months after the HCV RNA has ceased to be detected in the blood. It is still unknown if the virus disappears from the body completely. Almost all spontaneously recovered from acute hepatitis C patients can observe a strong polyclonal specific response of T cells, which convincingly proves the relationship between the duration and strength of a specific cellular immune response and the favorable outcome of the disease. In contrast, the cellular immune response in patients with chronic HCV infection is usually weak, narrow-focus and / or short-lived. Factors of the virus and host, causing the inability of an immune response to control HCV infection. Insufficiently 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. Resulting in the ability of the virus to prolonged (perhaps, lifelong) persistence in the human body.

In HCV infection, there may be a variety of extrahepatic lesions caused by immunopathological reactions of immunocompetent cells, which are realized either by immunocellular (granulomatosis, lymphomacrofagal infiltrates) or by immunocomplex reactions (vasculitis of different localization).

Morphological changes in the liver with viral hepatitis C are nonspecific. Lymphoid infiltration of the portal tracts with the formation of lymphoid follicles, lymphoid infiltration of the lobules, step necrosis, steatosis, damage to small bile ducts, liver fibrosis, which are found in various combinations and which determine the degree of histological activity and the stage of hepatitis, are observed predominantly. Inflammatory infiltration in chronic HCV infection has its own peculiarities: lymphocytes predominate in the portal tracts and around the foci of damage and death of hepatocytes, which reflects the involvement of the immune system in the pathogenesis of liver damage. In hepatocytes, fatty dystrophy is observed, with the steatosis of the liver being more pronounced when infected with the genotype Za, in comparison with genotype 1. Chronic hepatitis C, even with a low degree of histological activity, may accompany the development of liver fibrosis. Not only the portal and periportal lobes are exposed to fibrosis, and periveneular fibrosis is often detected. Heavy fibrosis leads to the development of cirrhosis (diffuse fibrosis with the formation of false lobules), against which development of hepatocellular carcinoma is possible. Cirrhosis of the liver develops in 15-20% of patients with marked inflammatory changes in liver tissue. At present, in addition to the morphological description of the obtained biopsies, several numerical estimation systems have been developed that allow semiquantitative (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 determine the prognosis of the disease, strategy and tactics of antiviral therapy.

[20], [21], [22], [23], [24], [25], [26], [27]

Symptoms of the hepatitis C

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

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

Symptoms of acute hepatitis C

In the pre-zheltushnom period most often prevails asthenovegetative syndrome, manifested by weakness, rapid fatigue. Dyspeptic disorders often occur: decreased appetite, discomfort in the right upper quadrant, nausea and vomiting. The arthralgic syndrome is much less common, itchy itch is possible. The icteric period proceeds much more easily than with other parenteral hepatitis. The leading symptoms of an acute period are weakness, decreased appetite and a feeling of discomfort in the abdomen. Nausea and itching are met in a third of patients, dizziness and headache - one in every five, vomiting - for every tenth patient. Almost all patients have enlarged liver, 20% have spleen. For acute hepatitis C, the same changes in biochemical parameters are characteristic, as with other parenteral hepatitis: an increase in the level of bilirubin (in the case of anicterless form, the amount of bilirubin corresponds to normal indices), a significant increase in ALT activity (more than 10 times). Often, the wavy character of hyperfermentemia is noted, which is not accompanied by deterioration of well-being. In most cases, the level of bilirubin is normalized by the thirtieth day after the appearance of jaundice. Other biochemical indicators (sediment samples, total protein and protein fractions, prothrombin, cholesterol, alkaline phosphatase) are usually within normal limits. Sometimes an increase in GGT content is recorded. In the hemogram the tendency to leukopenia, in the urine, reveal bile pigments.

Acute hepatitis C proceeds mainly in moderate form, in 30% of patients - in mild. Perhaps the serious course of the disease (rarely), and fulminant acute hepatitis C, leading to death, is very rare. In the natural course of viral hepatitis C, 20-25% of patients with acute hepatitis C recover spontaneously, 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 a spontaneous recovery if, if a patient who does not receive specific antiviral therapy, against a background of good health and normal size of the liver and spleen, determine normal biochemical parameters of the blood, and in the serum does not HCV RNA is detected for at least two years after acute hepatitis C. Factors associated with spontaneous elimination of the virus: young age, female gender and a certain combination of genes of the main histocompatibility complex.

[28], [29], [30], [31]

Symptoms of chronic hepatitis C

In 70-80% of individuals. Who transferred acute form of the disease, the formation of chronic hepatitis, which is the most common pathology among chronic viral liver lesions. The formation of chronic hepatitis C can accompany the normalization of clinical and biochemical indicators after an acute period, however, hyperfermentemia and HCV RNA in the blood serum subsequently reappears. Most patients with biochemical signs of chronic hepatitis C (70%) have a favorable course (mild or moderate inflammatory activity in liver tissue and minimal fibrosis). A remote 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% in 20 years, 20-30% in 30 years), cirrhosis of the liver occurs, which can be the cause of death. Decompensated hepatic cirrhosis is associated with increased mortality and is an indication for liver transplantation. In 70% of patients the cause of death is hepatocellular carcinoma, hepatic-cell insufficiency and bleeding.

For patients with chronic hepatitis C, the risk of 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 the progression of fibrosis: 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 intake of more than 40 grams of pure ethanol. Another unfavorable factor is overweight, which causes the development of steatosis of the liver, which, in turn, contributes to a more rapid formation of fibrosis. The likelihood of progression of the disease has no connection with the HCV genotype or viral load.

The peculiarity of chronic hepatitis C is a latent or malosymptomatic course for many years, usually without jaundice. Increased activity of ALT and ACT, 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, when examined before surgery, when undergoing medical examination, etc. . Sometimes patients fall into the doctor's field of vision only when forming cirrhosis of the liver and when signs of its decompensation appear.

Chronic HCV infection may be accompanied by normal ALT activity in repeated studies for 6-12 months, despite the continued replication of HCV RNA. The proportion of such patients among all patients with chronic infection is 20-40%. Part of this category of patients (15-20%) with liver biopsy can reveal serious fibrotic changes. Puncture liver biopsy is an important diagnostic method that allows to identify patients with progressive serious liver damage requiring urgent antiviral therapy. The rate of progression of liver fibrosis in patients with normal ALT activity appears to be lower than in patients with increased activity.

The extrahepatic symptoms of hepatitis C are met, according to different authors, in 30-75% of patients. They can come to the fore in the course of the disease and determine the prognosis of the disease. The course of chronic hepatitis C can accompany such immuno-mediated extrahepatic manifestations as mixed cryoglobulinemia, red flat lichen, mesangiocapillary glomerulonephritis. Late skin porphyria, rheumatoid symptoms. The role of HCV in the development of B-cell lymphoma, idiopathic thrombocytopenia, endocrine (thyroiditis) and exocrine glands (primarily involvement of the salivary and tear glands, including within the framework of Sjogren's syndrome), eyes, skin, muscles, joints , nervous system, etc.

Symptoms of hepatitis C of anicteric shape

The disease begins gradually, complaints of fatigue, worsening of appetite, and abdominal pain may be noted. A few days later on the foyer of developed asthenic and dyspeptic phenomena there is an increase and consolidation of the liver, which protrudes 2-5 cm below the costal arch, and in some patients an increase in the spleen is observed simultaneously.

The frequency of clinical symptoms (%) in the midst of hepatitis C

Symptom	The form
	Anicteric	Easy	Medium-heavy
Headache	-	6.0	14.0
Weakness	6.9	18	47.0
Anxiety	-	-	4.7
Impairment of appetite	13.8	39.0	56.4
Vomiting	-	15.0	23.5
Stomach ache	6.9	12.0	56.4
Enlargement of the 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
Sensitivity of the liver	17.2	63.0	47.0
Consistency of the liver: 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

From the indicators of functional liver samples, hyperfermentemia (a 3-10-fold increase in aminotransferase activity) attracts attention at a normal level of bilirubin. Sediment tests are little changed.

Biochemical indicators in the midst of acute hepatitis C

Index	The 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, ED / L	290 ± 35	330 ± 28	400 ± 41
ACT, U / l	160 ± 45	250 ± 30	320 ± 53
Timole sample, U / l	6.3 ± 1.1	7.8 ± 1.6	12.0 ± 2.4

Light form

The disease begins with the appearance of weakness, worsening appetite, sometimes - pain in the abdomen. The body temperature remains normal or increases no more than 38 ° C. A few days later, an increase in the liver is found.

The duration of the pre-zheltushnogo period - from 3 to 7 days. On the average 4.3 ± 1.2 days. With the appearance of jaundice, the condition of patients does not worsen, intoxication does not increase. In icteric period, moderately expressed hepatolyenal syndrome is defined. The liver is compacted, sensitive, protruding from the hypochondrium for 1-3 cm; the spleen is palpable in most patients at the edge of the costal nougat and in the individual - 1-3 cm below the rib margin.

In the serum, the bilirubin content averages 40.3 ± 5.0 μmol / l, mail solely due to the conjugated fraction, the activity of hepatic cell enzymes increases no more than 3-10 times. Indices of thymol test within normal limits or slightly increased.

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

Medium-heavy form

In the initial period of the disease, asthenic and dyspeptic phenomena (lethargy, adynamia, dizziness, loss of appetite, repeated vomiting, abdominal pain) are typical, in some patients it is possible to raise the body temperature to 38-39 C. The pre-egg period lasts 5-8 days, average 5.7 ± 1.7 days.

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

In biochemical blood analysis, a 5-10-fold increase in the level of bilirubin is registered, on average 119.0 + 12.3 μmol / L, mainly conjugated, high activity of hepatic cell enzymes, while ALT and ACT values exceed the norm by 5-15 times , the indices of thymol test were moderately increased, the prothrombin index index was reduced to 60-65%.

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

Heavy Form

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

In the serum, the level of bilirubin increases more than 10-fold, due to both the conjugated and non-conjugated fraction; characterized by high hyperfermentemia and a decrease in the prothrombin index to 50% or more.

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

Malignant form

In the literature there are only isolated reports of the development of malignant (fulminant) hepatitis C in both adults and children. It is reported that the clinical manifestations of fulminant hepatitis C do not differ from those of HBV infection.

Subclinical form of hepatitis C

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

Stages

There are acute, prolonged and chronic course of the disease.

The acute course of hepatitis C is characterized by a relatively rapid reversal of clinical and laboratory parameters of hepatitis with recovery and complete restoration of the functional state of the liver in terms of up to 3 months. From the onset of the disease.

Options for benign disease can include:

• recovery with complete structures and functional restoration of the liver;
• recovery with residual liver fibrosis (residual fibrosis);
• convalescence with lesion of bile ducts (dyskinesia, cholecystitis, cholangitis, etc.).

The prolonged course of hepatitis C is often manifested in the fact that after the disappearance of jaundice and, it would seem, the end of the acute period, hyperfermentemia is delayed. The condition of the patients is quite satisfactory in these cases, the liver is moderately increased, but the spleen usually stops palpating. Hyperfermentemia may be retained for 6-9 or even 12 months, but eventually the enzymes normalize their activity and recover completely.

The chronic course of hepatitis C is established after the active more than 6 months of the process is ascertained in the liver. Most clinicians indicate a high incidence of chronic hepatitis C - from 40 to 56-81%. And one of the frequent options is considered asymptomatic, from the very beginning of the disease, hyperfermentemia, which persists for several years, then increasing, then weakening.

According to the research, in 42 children (53.4%) after the abating of the acute period, the increased activity of aminotransferases persisted and in 10 the HCV RNA in the blood serum continued to be detected; while practically all patients had palpable dense, enlarged liver. Approximately equally of all forms of acute hepatitis C formed a chronic process. It should be noted that in all children, both recovered, and with the outcome of the disease in a chronic form, antibodies to the hepatitis C virus were detected in the blood serum.

Apparently, it can be argued as a natural phenomenon that the transition of acute manifest Hepatitis C into a chronic form. Strict justification for this fact has not yet been given, but an understanding of this pattern will be obtained in the study of HCV infection, taking into account genotypes of RNA of hepatitis C virus.

[32]

Forms

• By the presence of jaundice in the acute phase of the disease:
  • Icteric.
  • Anxious.
• By the duration of the current.
  • Acute (up to 3 months).
  • Prolonged (more than 3 months).
  • Chronic (more than 6 months).
• By gravity.
  • Light.
  • The middle-aged.
  • Heavy.
  • Fulminant.
• Complications.
  • The hepatic coma.
• Outcomes.
  • Recovery.
  • Chronic hepatitis C.
  • Cirrhosis of the liver.
  • Hepatocellular carcinoma.

By the nature of the clinical manifestations of the acute phase of the disease distinguish typical and atypical hepatitis C. Typical include all cases of the disease, accompanied by clinically apparent jaundice, and to atypical - jaundiced and subclinical forms.

All typical variants of the disease, depending on the severity of symptoms (intoxication, jaundice, hepatosplenomegaly, etc.) and biochemical changes (increase in bilirubin level, decrease in prothrombin index, etc.) are usually divided into light, moderate, severe and malignant (fulminant) forms.

Depending on the duration, acute, prolonged and chronic hepatitis C are distinguished.

[33], [34], [35], [36],

Diagnostics of the hepatitis C

Clinical symptoms of acute hepatitis C in a significant part of patients are poorly expressed, so the diagnosis of acute hepatitis C is based on a comprehensive assessment of the epidemiological history in terms that correspond to the incubation period, jaundice, increased bilirubin levels, ALT increase more than 10 times, the presence of newly identified markers viral hepatitis C (anti-HCV, HCV RNA) with the exclusion of hepatitis of a different nature. Given 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 make it possible to distinguish acute hepatitis from exacerbation of chronic hepatitis, the diagnosis of acute hepatitis C is established in those cases when along with the characteristic clinical, epidemiological and biochemical data when a primary blood serum test, no antibodies to HCV appear, which appear 4-6 or more weeks after the onset of the disease. To diagnose acute hepatitis C, you can resort to the detection of viral RNA by PCR, as 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, much more sensitive and specific, makes it possible to detect anti-HCV in the blood serum after 7-10 days from the onset of jaundice. Anti-HCV can be detected in both acute hepatitis C and chronic hepatitis C. In this case, anti-HCV antibodies IgM are equally often found in patients with both acute and chronic hepatitis C. Thus, the detection of anti-HCV IgM can not be Used as a marker of the acute phase of viral hepatitis C. In addition. Anti-HCV can circulate in an isolated way in the blood of patients who recovered from acute hepatitis C or are in a remission phase after eliminating HCV RNA as a result of antiviral therapy. Modern test systems can increase the detectability of anti-HCV in 98-100% of immunocompetent infected individuals, while in immunocompromised patients the detection rate of anti-HCV is much lower. It is necessary to remember the possibility of false-positive results in the response to anti-HCV, which can be 20% or more (in cancer patients, in autoimmune diseases and immunodeficiencies, etc.).

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

Standard Diagnosis of Acute Hepatitis C

Mandatory laboratory tests:

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

Additional laboratory tests:

• Immunological study: HCV RNA (qualitative analysis), antidetal 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 blood state;
• coagulogram.

Instrumental research:

• Ultrasound of the abdominal cavity;
• ECG;
• chest X-ray.

[37], [38], [39], [40], [41],

The standard of diagnosis of chronic hepatitis C

Mandatory laboratory tests:

• clinical blood test;
• biochemical blood test: bilirubin, ALT, ACT, thymol assay;
• Immunological study: Anti-HCV; HBcAg;
• clinical analysis of urine and bile pigments (bilirubin).

Additional laboratory studies;

• 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), antidetal total, 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;
• feces for hidden blood.

Instrumental diagnostics (optional):

• Ultrasound of the abdominal cavity organs:
• ECG;
• Chest X-ray:
• percutaneous puncture liver biopsy:
• EGDS.

Differential diagnosis

Differential diagnosis is performed with other viral hepatitis. When the diagnosis is made, first of all, the relatively easy course of the disease with a much lower degree of severity of intoxication syndrome, with rapid normalization of biochemical parameters, is taken into account in acute hepatitis C. The dynamics of markers of viral hepatitis plays an important role in differential diagnosis.

Indications for consultation of other specialists

Presence of jaundice, discomfort or pain in the abdomen, increased activity of ALT and ACT, absence of markers of viral hepatitis may require consultation of a surgeon to exclude the podpechenochnogo nature of jaundice.

Treatment of the hepatitis C

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

Medical treatment of hepatitis C

As an etiotropic agent in the treatment of acute hepatitis C, standard interferon alpha-2 is used. Increase the number of recovered (up to 80-90%) of acute hepatitis C with the following treatment regimens:

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

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

A complex of therapeutic measures for chronic hepatitis C includes the implementation of basic and etiotropic (antiviral) therapy. Basic therapy involves diet (table number 5), course use of funds that normalize the activity of the gastrointestinal tract, affecting the functional activity of hepatocytes (pancreatic enzymes, hepatoprotectors, cholagogue for the restoration of intestinal microflora, etc.). It should also limit physical activity, provide patients with psychoemotional and social support, and treat associated diseases. The purpose of carrying out etiotropic therapy for chronic hepatitis C is suppression of viral replication, eradication of the virus from the body and cessation of the infectious process. This is the basis for slowing the progression of the disease, stabilizing or regressing pathological changes in the liver, preventing the formation of liver cirrhosis and primary hepatocellular carcinoma, and improving the quality of life associated with health.

Currently, the best option for conducting 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 treatment for chronic hepatitis C is standard interferon alpha-2, a combination of standard interferon alpha-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 either subcutaneously or intramuscularly. Pegylated interferon alfa-2a is prescribed in a dose of 180 μg, pegylated interferon alpha-2b - from the calculation of 1.5 μg / kg - once a week under the skin for 48 weeks with genotypes 1 and 4 for 24 weeks with other genotypes. Ribavirin is taken daily at a dose of 800-1200 mg in two divided doses, depending on the HCV genotype and body weight.

It is of fundamental importance to establish indications for etiotropic therapy of chronic genotype C and to select an adequate program for its conduct. In each case, a careful differentiated approach is needed in determining the group of persons to be treated. According to the recommendations of the conciliation conferences held in 2002, antiviral treatment of hepatitis C is performed only in adults with chronic hepatitis C, with HCV RNA in the blood serum and in the presence of histological signs of liver damage.

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

Treatment is prescribed for patients with chronic hepatitis at the stage F2 or F3 in the METAVIR system, regardless of the degree of activity of necrotic liver inflammation, as well as patients with cirrhosis of the liver (for the purpose of obtaining a virologic response, stabilizing the process in the liver, preventing hepatocellular carcinoma). After the initial course of treatment in the absence of a virologic response, but in the presence of a biochemical response, supportive interferon alpha-2 therapy may be prescribed to slow the progression of the disease. Predictors of response to treatment for chronic hepatitis C are host factors and virus factors. So. Patients aged less than 40 years, patients with a short duration of the disease and patients are more likely to respond to interferon therapy. The disease is more difficult to treat in patients who abuse alcohol, people with diabetes, steatosis of the liver, obesity. Therefore, a modification of the diet before treatment can improve its results. The response rate is higher in patients with poor fibrosis than with stage 3-4 fibrosis or with cirrhosis. However, half of patients with liver cirrhosis manage to achieve a virologic response (in genotype 1 - in 37%, with not more than 1 in more than 70% of patients), therefore this category of patients should also receive antiviral therapy, although the tactics of it should be, if necessary, correction. The frequency of a successful virologic response when treated with standard and pegylated interferon alpha-2 in combination with ribavirin or without it depends on the HCV genotype and the viral load. Most often, patients with genotypes 2 and 3 respond to treatment of hepatitis C, in patients with genotypes 1 and 4 the probability of a successful virologic response is significantly lower. Patients with high viral load (> 850 thousand IU / ml) respond worse to treatment than patients with 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 a full course of treatment - more than 80% of the dose of drugs for more than 80% of the planned duration of treatment.

Evaluation of the effectiveness of specific treatment of hepatitis C is carried out based on several criteria - virologic (disappearance of HCV RNA from serum), biochemical (normalization of ALT level) and morphological (decrease in the index of histological activity and fibrosis stage). There may be several options for responding to the antiviral treatment of hepatitis C. If normalization of ALT and ACT levels and the disappearance of HCV RNA in the blood serum are recorded immediately after the end of therapy, then they say complete remission, about the biochemical and virologic response at the end of treatment. A stable biochemical and virological response is noted if, after 24 weeks (6 months) after stopping the course of treatment in the serum, a normal level of ALT is detected and HCV RNA is absent. Relapse of the disease is recorded when the level of ALT and ACT rises and / or HCV RNA appears in the serum after discontinuation of treatment. Absence of therapeutic effect means absence of normalization of the level of ALT and ACT and / or retention of HCV RNA in the serum on the background of the treatment. Forecasting the effectiveness of antiviral therapy is possible by assessing the early virologic response. The presence of an early virologic response suggests the absence of HCV RNA or a decrease in viral load by more than 2xIg10 in serum after 12 weeks of treatment. When registering an early virologic response, the likelihood of effective antiviral therapy is high, while its absence indicates a low chance of achieving a successful virologic response, even if the course of treatment of the patient 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 initiation of antiviral treatment.

The duration of treatment for hepatitis C depends on the HCV genotype. In genotype 1, if there is no HCV RNA in the blood serum after 12 weeks from the start of treatment, 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 is reduced by at least 2xlgl0 compared to the baseline, but HCV RNA continues to be detected in the blood, it is necessary to conduct a second study of HCV RNA at the 24th week of treatment.

If HCV RNA remains positive after 24 weeks, treatment for hepatitis C should be discontinued. The absence of an early virologic response allows us to accurately predict the ineffectiveness of further therapy, and therefore treatment should also be discontinued. At the 2nd or 3rd genotype, combined therapy with interferon and ribavirin is carried out for 24 weeks without determining the viral load. At the 4th genotype, as well as at the 1-m, the combined treatment of hepatitis C is recommended for 48 weeks. During treatment with interferon-type drugs and ribavirin, undesirable events are possible. A mandatory condition for ribavirin therapy is the use of contraception by both partners throughout the treatment period (it is also recommended to avoid pregnancy during another 6 months after the end of treatment). The side effects of interferon and ribavirin are sometimes forced to reduce their doses (temporarily or permanently) or to cancel drugs. During the treatment of hepatitis C, patients should be monitored, biochemical control performed (every two weeks at the beginning of treatment, then monthly), virologic control (in genotype 1 - 12 weeks from the start of therapy, in genotype 2 or 3 at the end of treatment ). In some cases, at the end of the course of treatment, a repeated puncture liver biopsy is performed to evaluate the histological pattern. Investigate the hemogram, once every four months - the concentration of creatinine and uric acid, TTG, ANF.

Due to the presence of common ways of transmission of viruses of chronic hepatitis C is often accompanied by the infection of HBV and / or HIV. Co-infection increases the risk of developing cirrhosis, terminal hepatic-cell insufficiency and hepatocellular carcinoma, as well as mortality of patients compared with those in patients with HCV monoinfection. Preliminary data suggest that the combination of pegylated interferon and ribavirin allows virological and / or histological response to be achieved in HIV-infected patients with chronic hepatitis C. When prescribing antiviral therapy for patients with chronic viral hepatitis in case of 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 number 5), detoxification therapy is carried out in the form of abundant drinking or intravenous infusions of 5-10% glucose solution, polyionic solutions and ascorbic acid. By individual indications, protease inhibitors are used. Antispasmodics, haemostatic agents, hyperbaric oxygenation, hemosorption, plasmapheresis, laser therapy.

Clinical examination

The peculiarity of clinical examination of patients with viral hepatitis C is the duration of the procedure. Patients with viral hepatitis C are monitored for life because of the absence of reliable recovery criteria in order to identify signs of reactivation of the infection and correct observation and treatment tactics.

[42], [43], [44]

What do you need to know for a patient with viral hepatitis C?

You have suffered acute hepatitis C, and you need to know that the disappearance of jaundice, satisfactory laboratory performance and well-being are not indicative of complete recovery, since a full restoration of liver health occurs within 6 months. To prevent an exacerbation of the disease and the transition to a chronic form, it is important to strictly follow the medical recommendations related to follow-up and examination in a polyclinic, day regimen, diet, and working conditions.

Mode and diet for hepatitis C

Half-bed mode for mild and moderate acute hepatitis C. In severe acute hepatitis C strict bed rest. With chronic hepatitis C - compliance with the regime of work and rest, it is not recommended to work in the night shift and in industries associated with toxic products, business trips, lifting weights, etc.

Diet sparing (for culinary processing and exclusion of irritants), table number 5.

Return to work, associated with great physical stress or occupational hazards, is permissible not earlier than 3-6 months after discharge. Before this, it is possible to continue working in the mode of easy work.

After discharge from the hospital should beware of hypothermia and avoid overheating in the sun, it is not recommended to travel to southern resorts during the first 3 months. Also, you should beware of taking medications that have an adverse (toxic) effect on the liver. After normalization of biochemical parameters of blood for 6 months, participation in sports competitions is prohibited. Those who have recovered with acute hepatitis B are exempted from preventive vaccinations for 6 months. Sports activities are limited only by a complex of therapeutic gymnastics.

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

Allowed:

• milk and dairy products in all kinds;
• boiled and stewed meat - beef, veal, chicken, turkey, rabbit;
• boiled fresh fish - pike, carp, pike perch and sea fish (cod, perch);
• vegetables, vegetable dishes, fruit, sauerkraut;
• cereals and flour products;
• vegetable soups, cereals, dairy;

It is necessary to limit the use:

• meat broths and soups (low-fat, not more often 1-2 times a week);
• butter (not 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, only not sharp);
• meat products (sausages beef, sausage doctor's, dietary, dining room);
• caviar of salmon and sturgeon, herring:
• tomatoes.

Prohibited:

• alcoholic beverages:
• all kinds of fried, smoked and pickled products;
• pork, lamb, goose, duck;
• spicy condiments (horseradish, pepper, mustard, vinegar);
• confectionery products (cakes, pastries);
• chocolate, chocolate sweets, cocoa, coffee;
• tomato juice.

Medical supervision and control

Examination of survivors of viral hepatitis C is carried out at 1, 3, 6 months, and then, depending on the conclusion of the dispensary. Withdrawal taking into account with a favorable outcome is not earlier than 12 months after discharge from the hospital.

Remember that only the supervision of an infectious disease doctor and a regular laboratory examination will determine the fact of your recovery or the transition of the disease to a chronic form. If the doctor prescribes antiviral treatment for hepatitis C, you must strictly adhere to the regimen of the drug and regularly come to laboratory monitoring of blood counts, as this will minimize the chance of a side effect of the drug and provide control over the infection.

To appear for a laboratory examination is necessary at a doctor's appointed day on an empty stomach.

Your first visit to the polyclinic is prescribed by your doctor.

The established control periods for repeated medical examinations at a polyclinic or a hepatological center are mandatory for all who have transferred viral hepatitis C. If necessary, you can contact the office of follow-up hospital observations, or a hepatology center, or a polyclinic clinic as well, in addition to these terms.

Be attentive to your health!

Strictly adhere to diet and diet!

Be on regular check-ups!

Prevention

Prevention of hepatitis C is particularly relevant because of the epidemiological prevalence of the disease, and because of the lack of a vaccine against a deadly infection.

A nonspecific method is the ubiquitous use of disposable medical instruments that carry out procedures related to blood. In addition, blood transfusion, hemodialysis is prescribed only on strict indications, when the risk of lethality exceeds the risk of infection with hepatitis C. All medical personnel are regularly equipped with disposable gloves, special tools for processing instruments and instruments of reusable use.

Specific prophylaxis of hepatitis C is the strict control of donor blood and the identification of possible virus carriers. In many developed countries, these measures are fixed in official documents of the health authorities. All blood products to prevent the transmission of HCV are treated by warming up or by chemical detoxification. It is also considered effective to vaccinate hepatitis C virus carriers with hepatitis A and B vaccinations.

Prevention of hepatitis C involves a total examination for possible virus carrying of people at risk: 

• Persons registered for the use of injecting drugs.
• HIV-infected patients.
• Patients with diagnosed hemophilia.
• Patients undergoing hemodialysis.
• Patients who underwent organ transplantation before 1992.
• Patients who underwent blood transfusion (blood transfusion) before 1992.
• Infants whose mother is infected with HCV.
• Medical personnel who have contact with blood.

It is also desirable to conduct a screening for the detection of hepatitis C virus in people who have a history of STDs - sexually transmitted diseases.

Vaccination against hepatitis C

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

[45], [46], [47],

Forecast

The statistics that are systematically collected and analyzed by WHO are not yet comforting. The prognosis of hepatitis C in figures is as follows: 

• The active, acute course of the disease is the development of liver cirrhosis in 20% of cases, of which more than 5% result in carcinoma.
• 60-80% of all infected with the hepatitis C virus have a chronic form of the disease.
• 70-75% of the total number of patients have pathological changes in liver structure and function without malignancy (cancer development).
• In 20% of patients with chronic HCV, cirrhosis develops.
• 30-35 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 significantly improved with the introduction of antiviral therapy, the timely appointment of which allows recovery in 80-90% of patients. If the acute phase of infection was not diagnosed and patients do not receive antiviral therapy, the prognosis is worse - 80% of patients develop chronic hepatitis C, in 15-20% of patients with progressive course of the disease it is possible to form liver cirrhosis within 20-30 years. On the background of cirrhosis with a frequency of 1-4% per year, primary hepatocellular carcinoma occurs.

[48], [49], [50]