Chronic hepatitis C: clinical picture, diagnosis, treatment

Chronic hepatitis is a very common disease: it affects at least 5% of the population of our planet. The concept of chronic hepatitis unites a whole group of liver diseases. They can be caused by different reasons and have different clinical signs, but they last for at least six months without any improvement.

Among the forms of chronic hepatitis are:

• persistent (this is a benign, inactive form);
• chronic active (close to acute hepatitis in its manifestations);
• chronic cholestatic.

Symptoms of chronic hepatitis

In the first case, chronic hepatitis manifests itself weakly, its symptoms are loss of appetite, heaviness and pressure in the right hypochondrium, caused by an increase in the size of the liver and its moderate hardening, and dyspepsia. Chronic active hepatitis is accompanied by a wider range of symptoms: weakness and fatigue; Some foods are not tolerated by patients (for example, fats); dyspepsia, the appearance of spider veins and nosebleeds, which are caused by deterioration of blood clotting; skin itching and increased body temperature, while not only the liver, but also the spleen enlarges. With lupoid hepatitis, as one of the forms of manifestation of chronic active hepatitis, there are furunculosis, lymphadenopathy, hormonal disorders, fever, abdominal pain, etc.

Skin itching, jaundice, lightening of stool and dark urine, soft nodular formations on the skin accompany chronic cholestatic hepatitis.

Viral hepatitis

Which doctors should I contact?

Any viral hepatitis is an infectious disease and is treated primarily by infectious disease doctors.
In addition, there are other specialists in liver diseases (gastroenterologists and hepatologists) who also take an active part in the treatment of patients suffering from viral hepatitis. Treatment of viral hepatitis
For mild acute hepatitis, treatment can be carried out on an outpatient basis; moderate and severe forms are treated in a hospital. In case of chronic pathology (beyond a significant exacerbation), treatment is carried out at home. In cases of severe exacerbation or decompensation, hospitalization in an infectious diseases hospital is indicated.

Basic treatment is prescribed, which includes a gentle regime and a specialized diet - exclude fried, smoked, pickled foods, refractory fats (pork, lamb), alcoholic and carbonated drinks. It is recommended to drink plenty of fluids (up to 2–3 liters per day).

Detoxification measures are used (intravenous administration of hemodez, glucose solution with vitamin C or Essentiale, lactulose is prescribed). If necessary, sorbents, hepatoprotectors, antioxidants, diuretics, probiotics, antihistamines, anti-inflammatory and hormonal agents, and vitamins are recommended.

Alpha interferon has immunomodulating and antiviral effects, inhibits the synthesis of viral proteins, and enhances the activity of natural killer cells in hepatitis B and C.

In the case of a chronic course of the disease, it may be necessary to prescribe drugs with direct antiviral action, leading to the complete disappearance of the hepatitis C virus or persistent suppression of viral replication in hepatitis B and D. The hepatitis B virus is able to integrate into human genetic material, and therefore completely recover from this disease fails. Treatment of hepatitis B with delta agent is one of the most difficult tasks in hepatology today.

Complications

Complications of viral hepatitis can include functional and inflammatory diseases of the biliary tract, as well as hepatic coma, which occurs due to massive necrosis of liver cells and leads to death in almost 90% of cases. Hepatitis B and C are dangerous due to the development of a chronic process and are the most common cause of cirrhosis and liver cancer.

The most severe course of the disease is caused by a combination of two or more viruses. In this case, the prognosis is extremely unfavorable. Often the signs of chronic viral hepatitis are mild, which allows a person to ignore the disease for the time being. Often, obvious clinical manifestations of the disease are detected already at the stage of liver cirrhosis.

In addition to the development of cirrhosis and liver cancer, a connection between chronic hepatitis C and B-cell lymphoma has been proven - damage to the endocrine glands, organs of vision, skin, muscles, joints, nervous system, and bile ducts.

Prevention of viral hepatitis

Today, the most effective method of preventing viral hepatitis is vaccination:

• The hepatitis A vaccine is administered twice and provides protection against the disease for up to 20 years. In Russia, vaccination against viral hepatitis A is included in the National Calendar of Preventive Vaccinations for epidemic indications.
• Vaccination against hepatitis B (N532) protects not only against the hepatitis B virus, but also against the delta agent. In Russia, vaccination is carried out within the framework of the National Calendar of Preventive Vaccinations. If no contraindications are identified for the newborn, the first vaccination is given in the maternity hospital, on the first day of life. The second one is done one month later, and the third one 6 months after the start of vaccination.
• There is no specific vaccine against hepatitis C. Several vaccines are in development.

Nonspecific prevention of viral hepatitis includes ensuring food and water safety (hepatitis A and E), careful testing of donor blood, sterile injection equipment and infection control (hepatitis B and C).
Hepatitis prevention measures are simple and accessible:

• Strict adherence to the rules of personal hygiene: washing hands before eating, after visiting the toilet, when returning from work, walking, refusing to use someone else’s manicure tool, toothbrush, razor.
• Avoid contact with the biological fluids of strangers. When treating wounds, use disposable gloves.
• Wash vegetables, berries, fruits, greens under strong pressure of tap water, rinse with boiled water.
• Drink only boiled or bottled water. Do not swim in polluted waters.
• If parenteral hepatitis is detected, it is necessary to examine the sexual partner and follow all prescriptions of the attending physician.
• Avoid contact with used syringes, needles and other medical and non-medical equipment.

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IMPORTANT!

The information in this section cannot be used for self-diagnosis and self-treatment. In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. To make a diagnosis and properly prescribe treatment, you should contact your doctor.

Signs of chronic hepatitis

Chronic hepatitis is characterized by weakness and fatigue, and asthenic syndrome manifests itself. The patient's condition worsens significantly if liver cirrhosis develops. Then the signs of chronic hepatitis become jaundice (yellowness of the sclera, icteric skin tone, darkening of urine, discoloration of feces, etc.), the abdomen enlarges. Sometimes hepatic encephalopathy develops; when the brain is damaged, its activity is disrupted, and hallucinations may occur.

Signs of chronic hepatitis do not appear immediately in patients; the first stages of the disease can be asymptomatic, which makes it especially dangerous. Chronic hepatitis is often detected during examination in connection with other diseases.

Publications in the media

Chronic viral hepatitis (CVH) is a chronic infectious disease caused by hepatotropic viruses; are characterized by a clinical and morphological picture of diffuse liver inflammation (lasting more than 6 months) and a symptom complex of extrahepatic lesions.

Etiology and epidemiology • CHV B (HBV infection). The causative agent is a DNA virus. The main route of transmission is parenteral, as well as through damaged mucous membranes and skin (perinatal, sexual contact, close household contact [shared razor, toothbrush, etc.]). At risk are drug addicts who inject drugs intravenously, homosexual men and persons in contact with blood and its products (for example, patients and medical personnel in surgery departments, hematology and hemodialysis centers). The incubation period is 1–6 months. Approximately 10% of patients experience a chronic course or long-term carriage of • CHV C (HCV infection). Previously, this hepatitis was designated by the term non-A non-B hepatitis, transmitted by the parenteral route. The causative agent is an RNA virus (HCV); isolated in 50–90% of cases of post-transfusion hepatitis. The routes of transmission (parenteral, sexual and possibly perinatal) are similar to those for chronic hepatitis B. The incubation period is from 2 weeks to 6 months. The chronic variant is observed in 30–50% and even 75% of patients (approximately 50% suffer from chronic active hepatitis); a significant proportion of patients develop cirrhosis of the liver • CHV D (HDV infection). The causative agent is a small defective RNA virus (HDV), d-virus); it is contagious only when infected with HBV (since, due to the incomplete genome, it uses HBV proteins for replication). The main route of transmission is parenteral (therapeutic and diagnostic procedures), as well as sexual and perinatal. The epidemiological significance of d-infection is great in regions where anti-d and HBS-Ag carriage is endemic. d-Infection exists in the form of acute infection with simultaneous infection with HBV and d-virus (co-infection) and acute infection with d-virus infection of HBV carriers or patients with chronic hepatitis B (superinfection). CVH D is characterized by a chronic, severe course • CVH E. The causative agent is an RNA virus isolated from patients with acute hepatitis in Mexico, Asia and Africa; outbreaks are observed in the CIS. The main mechanism of transmission is fecal-oral, the leading factor of transmission is infected water. People aged 15–40 years are affected. The incubation period is 15–45 days (average 40 days). The fulminant (fulminant) form of hepatitis is often registered in the 2nd–3rd trimester of pregnancy. Mortality among pregnant women can reach 10–20% • CHV G is classified as hepatitis transmitted parenterally; The disease is transmitted after a blood transfusion or organ transplant; the majority of those affected are adults. Giant multinucleated cells (syncytial giant cell hepatitis) are found in the liver. The virus was not isolated from liver biopsies; clinical and laboratory symptoms were not expressed. Hepatitis G is currently classified as non-A, non-B, non-C hepatitis.

Risk groups • Medical workers • Drug addicts • Recipients of blood and blood products (including patients with cancer and immunodeficiency conditions) • Newborns from mothers infected with HBV and HCV • Family members of persons infected with HBV and HCV • Patients on hemodialysis .

Clinical picture

• Signs of liver damage •• Active process - the liver is enlarged, dense, the edge is pointed, palpation is painful. With a decrease in activity, the size of the liver decreases, palpation is less painful (the consistency does not change significantly). Hepatomegaly is absent in patients with cirrhosis of the liver •• Pain in the liver area (the symptom is not constant, if present, the pain is constant, aching, sometimes intense, intensifies after physical activity) with an active process, with the subsidence of inflammatory phenomena - a decrease in the intensity of the pain syndrome •• Jaundice (parenchymal and secondary mechanical) is often accompanied by itchy skin, and scratches are found on the skin. Often CVH occurs without jaundice •• Telangiectasia and palmar erythema are caused by an increase in the concentration of estrogen and a change in the sensitivity of vascular receptors (opening and expansion of arteriovenous shunts). Their severity correlates with the activity of the process and does not indicate cirrhosis of the liver. Improvement in the functional state of the liver is accompanied by a decrease in the number of spider veins or their disappearance, hyperemia of the palms remains much longer (often until biochemical remission) •• Splenomegaly - with cirrhosis of the liver •• Dyspeptic syndrome (impaired detoxification function of the liver, concomitant pathology of the duodenum and pancreas ): nausea, worse after eating and taking drugs, vomiting, bitterness in the mouth, belching, diarrhea. Also, regardless of food intake, a feeling of heaviness and fullness in the right hypochondrium and epigastric regions is observed •• Asthenic syndrome: weakness, fatigue, decreased performance, irritability, decreased mood •• Amenorrhea, gynecomastia, decreased libido, associated with impaired metabolism of sex hormones in the liver •• Varnished tongue •• Minor liver failure syndrome: drowsiness, thrombohemorrhagic syndrome (bleeding and bruising on the skin, bleeding gums, nosebleeds, hematuria, uterine bleeding, etc.), transient jaundice and ascites; the syndrome is characteristic of an active inflammatory process in the liver •• Loss of body weight •• Increase in body temperature to subfebrile values.

• Extrahepatic manifestations •• Arthritis, arthralgia, polymyalgia •• Periarteritis nodosa •• Carditis •• Lung lesions: fibrosing alveolitis, pulmonary vasculitis, granulomatosis •• Pancreatitis •• Sjogren's syndrome •• Kidney damage: glomerulonephritis •• Skin lesions: late cutaneous porphyria, papular acrodermatitis (Gianotti-Crosti syndrome) •• Lesions of the endocrine system: autoimmune thyroiditis, ovarian dysfunction •• Raynaud's syndrome •• Damage to the nervous system: polyneuropathy, Guillain-Barre syndrome •• Secondary mixed cryoglobulinemia •• Hypoplastic or aplastic anemia.

Laboratory research. Biochemical blood test: increased ESR, hyperproteinemia, dysproteinemia (increased g-globulin content, increased thymol test, decreased blood albumin, decreased mercuric test), increased ALT and AST activity, increased conjugated (direct) bilirubin.

Serological studies

• Determination of CVH markers with the establishment of virus replication activity (in ELISA reactions, DNA hybridization, PCR). • HBV infection •• HBs-Ag (surface (Australian) HBV Ag) marks infection with the virus; appears in the blood 1.5 months after infection •• Ag Pre-S region HBs (Pre-S1 and Pre-S2) appear simultaneously or slightly earlier than HBsAg; mark an actively ongoing infection •• HBc-Ag (nuclear c-Ag) marks the replication of the virus in hepatocytes; discovered only during morphological examination of biopsy specimens or autopsy material of the liver; is not detected in free form in the blood •• HBe-Ag nuclear e-Ag (secretory part of HBc-Ag) indicates virus replication in hepatocytes; appears in serum almost simultaneously with HBs-Ag; may be absent in case of HBV infection caused by a mutant strain of the virus •• Anti-HBc (AT to nuclear Ag) is an important diagnostic marker of infection, especially with negative results of HBs-Ag indication •• Anti-HBc IgM (AT-immunoglobulins of class M to nuclear Ag ) is one of the earliest serum markers of chronic hepatitis B; the most sensitive marker of HBV infection; marks the replication of the virus and the activity of the process in the liver; its disappearance serves as an indicator of either the sanitation of the body from the pathogen, or the development of the integrative phase of HBV infection •• Anti-HBc IgG (AT-immunoglobulins of class G to nuclear Ag) persist for many years; indicate an existing or previously suffered infection •• Anti-HBe (AT to e-Ag) is a serological marker of virus integration; in combination with anti-HBc IgG and anti-HBs indicate the complete completion of the infectious process •• Anti-HBs (protective antibodies to surface Ag) indicate protection against infection; are formed during the vaccination process; may indicate the completion of a viral infection •• Anti-Pre-S (ATs to Pre-S1Ag and Pre-S2Ag) indicate the development of protective immunity at the completion of the infectious process; anti-PreS1 is registered simultaneously with anti-HBc, and anti-PreS2 - in the period of convalescence (evidence of recovery) •• HBV-DNA (HBV DNA) and DNA polymerase are diagnostic markers of virus replication •• HBV replication markers - HBe-Ag, anti-HBeAg IgM, HBV-DNA, HBV-DNA polymerase.

• HCV infection •• Anti-HCV (Ab to hepatitis C virus) appear in the blood within 6 months after infection (on average 3 months); indicate possible infection with the virus or a previous infection •• HCV RNA (HCV RNA) is a diagnostic marker of virus replication •• Markers of HCV replication are anti-HCV IgM and HCV RNA.

• HDV infection •• HDV-Ag (HDV Ag) - appears in the blood 3 weeks after infection; marks viral replication •• Anti-HDV IgM (class M antibody to hepatitis D virus) is considered a more reliable marker of HDV infection than HDV-Ag; indicate viral replication; recorded with high frequency during HDV superinfection as the most common cause of CHV D •• HDV-RNA (HDV RNA) is a diagnostic marker of virus replication •• Markers of HDV replication are anti-HDV IgM, HDV RNA.

Special methods • Ultrasound of the liver and spleen: increased echogenicity of the parenchyma, compaction along the liver vessels, with cirrhosis of the liver - splenomegaly • Radioisotope study of the liver: significant increase in cardioportal time (the time between peaks of activity above the heart and above the liver), enlarged liver, uneven accumulation of radiopharmaceuticals along the edges (fuzzy contours) • Laparoscopy: large compacted white or variegated liver with a pointed edge and a vague pattern of lobules, enhanced pattern of superficial vessels • Liver puncture biopsy: degeneration and necrosis of hepatocytes, lymphomacrophage infiltration and proliferation of connective tissue in the hepatic lobules. Changes are assessed using semi-quantitative methods (histological activity index according to RG Knodell et al and degree of fibrosis according to VJ Desmet et al.). Data from laparoscopy and liver puncture biopsy correlate with each other.

Differential diagnosis • Autoimmune hepatitis • Chronic drug-induced hepatitis • Primary biliary cirrhosis • Primary sclerosing cholangitis • Infectious mononucleosis • Primary and secondary liver tumors • Ischemic hepatitis • Chronic alcoholic hepatitis • Wilson's disease.

Treatment

• Etiotropic: IFN preparations (parenteral forms of natural and/or recombinant a- and b-IFN) - with a high degree of activity of the infectious process (presence of replication markers), as well as with extrahepatic lesions. The effectiveness of treatment is 20–60%.

• Criteria for the effectiveness of IFN treatment •• disappearance of HBV, HCV, HDV replication markers •• normalization of ALT and AST indicators •• improvement of the histological picture of the liver •• reduction or disappearance of symptoms of extrahepatic lesions.

• For chronic HBV infection, IFN is most effective in the presence of the following symptoms •• young age •• female gender •• onset of the disease in adulthood •• duration of the disease up to a year •• icteric form of the manifest manifestation of the disease •• high levels of ALT and AST in the serum blood •• low level of HBV-DNA (less than 200 pg/ml) •• absence of super- and coinfection with hepatitis C, D, G viruses, HIV infection, immunosuppressive therapy, renal failure, signs of cirrhosis.

• For chronic HCV infection, IFN is most effective in the presence of the following signs •• young age •• parenteral route of infection •• low concentration of HCV RNA •• HCV genotype 2a, 3, 4 (not 1b) •• normal iron content in the tissue liver and blood serum •• relatively short duration of the disease •• weakly expressed autoimmune component of inflammation •• absence of signs of cirrhosis, cholestasis.

• Chronic HDV infection is resistant to IFN therapy.

• Treatment regimens with IFN drugs •• For HBV infection ••• Recombinant a-IFN (interferon alpha-2b, for example, intron A) - 2.5–5 million (children up to 5–6 million) IU/m2 daily or 3 times/week subcutaneously or intramuscularly for 6 months ••• Natural a-IFN (interferon alpha-n1) 10 IU 3 times/week (for children - up to 10 IU/m2) for 12 weeks •• With HCV infections ••• Intron A 3 million IU/m2 3 times a week for 12–18 months ••• Interferon alpha-n1 3–5 IU 3 times a week for 48 weeks •• For HDV infection it is recommended intron A 5 million IU daily or 9–10 million IU 3 times a week for 12 months.

• Ways to increase the effectiveness of treatment with IFN drugs •• Combination with antiviral drugs with a different mechanism of action (for example, ribavirin) •• With low activity of the HBV replication process - preliminary treatment with prednisolone (for example, 30 mg / day for 3 weeks, then 15 mg/day for 1 week, then after 2 weeks treatment with IFN) •• For cholestasis, ursodeoxycholic acid is prescribed •• If the iron content in the liver tissue increases, bloodletting, antioxidants are prescribed.

Prevention • Prevention of the spread of infections transmitted parenterally (monitoring biological preparations for the presence of markers of viral replication, using disposable medical instruments, etc.).

Abbreviations • RFP - radiopharmaceutical • CHV - chronic viral hepatitis

ICD-10 • B18 Chronic viral hepatitis

City hospital of the resort city of Gelendzhik

Chronic hepatitis is an inflammatory degenerative liver disease that lasts more than six months. In 50% of cases, acute viral hepatitis with improper treatment turns into chronic hepatitis (mainly hepatitis C). The cause of chronic hepatitis can also be the long-term influence of toxic substances on the body (alcohol, salts of heavy metals, benzene, etc.). Long-term use of medications (sedatives, tetracycline antibiotics, antihypertensive, cytostatic, anti-tuberculosis, narcotic drugs) can lead to the development of chronic hepatitis. In addition, chronic hepatitis may be associated with metabolic disorders and autoimmune processes.

Symptoms of chronic hepatitis

On palpation, the liver is enlarged in size, and a dull pain is felt. Due to the accumulation of bile acids in the blood and tissues, bradycardia occurs, and symptoms such as a depressed mental state, irritability, and insomnia may appear. Characterized by decreased appetite, nausea, belching, flatulence, intolerance to fatty foods, alcohol, unstable stools, increased fatigue, decreased performance. The skin and sclera acquire a yellowish tint (jaundice). “Liver signs” include dilated capillaries in the form of stars on the cheeks, back, redness of the inner surfaces of the hands (“liver palms”). The spleen may become enlarged. Blood clotting is impaired, which is manifested by nosebleeds and easy bruising. Joint pain is possible.

Exacerbation of chronic hepatitis develops, first of all, with violations of the diet, heavy physical activity, alcoholic excesses, and stress. Remission (improvement in general condition) occurs after active treatment and exclusion of provoking factors. The patient does not experience any particular discomfort. Depending on his compliance with safety rules, the period of remission can be long (up to several years).

Diagnostics

• Biochemical blood test: characterized by an increase in bilirubin and liver enzymes.
• Ultrasound examination of the liver: signs of inflammation.
• For a more accurate diagnosis, a liver biopsy is performed, which makes it possible to assess the severity of inflammation, determine the presence of fibrosis or cirrhosis, and sometimes makes it possible to find out the cause of hepatitis.
• Serological blood test: detection of antibodies to hepatitis B and C viruses.
• Virological research: identification of the corresponding virus.
• Immunological study: detection of antibodies to components of liver cells.

Basic principles of treatment of chronic hepatitis

First of all, for the treatment of chronic liver hepatitis, it is necessary to follow the rules of behavior prescribed by the doctor. The main thing is to ensure peace; bed rest is recommended. Due to the fact that with strict adherence to bed rest, metabolic processes in the liver improve, liver cells recover faster.

One of the main principles of treatment of chronic hepatitis is diet. Food should be rich in proteins, carbohydrates and vitamins, fats should be limited, and some should be excluded altogether. Meals should be frequent, fractional, small portions. Of course, alcohol is strictly prohibited!

Drug therapy must be agreed with the attending physician. In severe cases of chronic hepatitis, the patient is usually hospitalized in a specialized department of the hospital, where he is prescribed combination treatment.

Prevention of chronic hepatitis

Prevention of chronic hepatitis consists of preventing acute viral hepatitis, timely treatment of acute hepatitis of any etiology, combating alcohol abuse, limiting the amount of medications taken to the required minimum, and caution when contacting hepatotoxic substances.

To prevent chronic hepatitis, the working day must be organized, moderate physical activity must be alternated with periods of rest, and it is strictly forbidden to work with pesticides (herbicides, pesticides, aggressive technical fluids). Twice a year, patients with chronic hepatitis should undergo preventive examinations, blood and urine tests.

For the prevention of chronic hepatitis, a very important condition is timely consultation with a doctor regarding diseases of various organs and systems and their full treatment.

GBUZ "Center for Medical Prevention" of the Ministry of Health of the Krasnodar Territory.

Chronic hepatitis C: clinical picture, diagnosis, treatment

Currently, both medical specialists and people who have nothing to do with medicine are interested in the problem of chronic HCV infection.

Hepatitis C affects at least 200 million people worldwide. The consequences of the disease may include chronic hepatitis, cirrhosis and primary liver cancer.

Epidemiology

The prevalence of chronic HCV infection around the globe varies from 0.5 to 2%. There are regions that have a higher prevalence of this disease: 6% in Zaire and Saudi Arabia, 16% in isolated settlements in Japan. In Russia, there is an increase in the incidence of hepatitis C (3.2 per 100 thousand population in 1994 and 19.3 in 1999). Sources of infection with viral hepatitis C are patients with acute and chronic forms of HCV infection, and these are mainly people who do not have jaundice and have an asymptomatic or minimally symptomatic course of the disease.

Currently, young people, mainly men aged about 20 years, are most often infected with HCV, approximately 40% of them become infected through intravenous drug use. The main route of HCV infection is parenteral. Thus, 6.1% of patients who received transfusions of blood and its components during cardiac surgery developed acute viral hepatitis C, and in 60% of them hepatitis took a chronic form.

There is also a risk of contracting hepatitis C through sexual contact, but it is small (5-8%). HCV transmission from mothers with acute or chronic infection is possible; this is also a rare phenomenon, occurring no more often than 5-6% of cases. The risk of infection through the above routes is inferior to that with hepatitis B.

In approximately half of patients, the route of HCV infection cannot be determined.

Hepatitis C virus

The hepatitis C virus belongs to the flavivirus family. The genome of the virus is represented by single-stranded RNA with a length of about 10,000 nucleotides. The hepatitis C virus causes disease only in humans. Under experimental conditions, the infection can be reproduced in great apes.

The virus population is heterogeneous. 6 genotypes (Simmonds classification), more than 90 subtypes and many variants of the virus, designated as quasispecies, have been identified. Territorial uneven circulation of hepatitis C virus genotypes has been recorded. In Russia, genotypes 1b and 3a of this virus are most often detected.

Determination of hepatitis C virus genotypes is of great importance for practical medicine. Although a clear correlation has not yet been established between genotypes and the level of viremia, patient characteristics, and severity of the disease, most researchers agree with the conclusions about the importance of virus genotypes as an important factor influencing the effectiveness of antiviral therapy.

It has not yet been possible to create a vaccine against hepatitis C due to the high variability of the hepatitis C virus (HCV).

Pathogenesis

The virus is believed to have a direct cytopathic effect and cause immune-mediated damage to hepatocytes. The high degree of chronicity of viral hepatitis C is due to some features of the action of the virus:

• the possibility of extrahepatic replication of the virus, including immunocompetent cells (cells, hematopoietic precursors, peripheral blood lymphocytes and monocytes, myofibroblasts);
• heterogeneity of genotypes and frequent mutations of the virus genome;
• induction of a cascade of immunopathological reactions;
• activation of lipid peroxidation processes in the liver.

During chronic HCV infection, the major variant of the virus can be neutralized, but then minor variants are generated. HCV quasispecies represent a moving target that is limited by the host immune system. The emergence of a new major quasispecies is accompanied by an increase in viremia and an increase in the titer of Ig M antibodies to viral proteins. Gradually this new major version is being replaced. This process leads to periodic wave-like viremia, accompanied by exacerbation of chronic hepatitis C (CHC) and an increase in antibody levels.

It is possible that the antiviral T cell response has a central role in HCV clearance, since neutralizing antibodies appear to be very often ineffective. T helper (Th) lymphocytes recognize viral antigenic peptides presented by the HLA class II complex on the surface membrane of antigen-presenting cells. Depending on the type of cytokine profile, Th cells are divided into two groups: Th1 and Th2. The former produce IFNγ and IL2, stimulating the T-cell response and cytotoxic T-lymphocyte activity, while the latter produce IL4 and IL10, stimulating the B-cell response. Thus, Th lymphocytes play a significant role in regulating the immune response. In patients whose disease progressed to the chronic stage, in the acute phase the virus-specific Th response was lower and Th2 type cytokines predominated.

In chronically HCV-infected patients, the content of virus-specific Th2 cells and their cytokines is significantly increased. Imbalance of Th1/Th2 cytokine production may play an important role in the immunopathogenesis of chronic HCV infection. A decrease in the level of IFNg and IL12 has been shown in CHC. This deficiency is a consequence of increased levels of IL10, a putative negative regulator for IFNγ. The increased content of Th2 cells in CHC can be reduced with combination therapy with ribavirin and IFNa. It was found that in patients with clinical and biochemical improvement after IFNa treatment, there was an increase in the level of Th1 cytokines.

Cytotoxic lymphocytes (CTLs) appear to play some role in limiting HCV replication. This response is not sufficient to completely clear the virus in chronic infection and may also cause liver damage. It is known that CTLs are able to quickly recognize and specifically lyse cells carrying HCV antigens without provoking significant inflammation, using perforin, FasL- and TNFα-based mechanisms.

TNFs are thought to induce cell apoptosis by mediating the release of free radicals from mitochondrial electron transport pathways and modulation of the synthesis of certain proteins. The interaction of the HCV nucleocapsid protein with the intracytoplasmic portion of the TNFb receptor is likely an evolutionarily selected mechanism by which the virus prevents premature apoptosis of the host cell. In the absence of available model cell cultures, direct cytopathicity of the hepatitis C virus cannot be fully investigated.

In the vast majority of cases of acute hepatitis C, the immune system fails to eliminate the virus. There is still no clear understanding of why this happens. Obviously, HCV has evolutionarily fixed abilities that ensure its persistence.

However, the immune system can have a significant impact on HCV infection. In 15% of cases of acute hepatitis C, it effectively destroys the virus, and in chronically HCV-infected people it provides moderate limitation of infection for almost 20 years. Perhaps the weakening of any part of the antiviral immune mechanisms allows the virus to actively influence the immune system. Long-term persistence of HCV can lead to the development of B-cell lymphoproliferative disorders, such as mixed cryoglobulinemia, malignant non-Hodgkin lymphoma, and the appearance of organ-specific and nonspecific autoantibodies. Thus, chronic HCV infection should be considered a multisystem disease.

Diagnostics

Laboratory diagnosis of hepatitis C is based on identifying specific markers of HCV infection (anti-HCV-IgM/G, HCV RNA) and should be carried out with diagnostic drugs of domestic or foreign production approved by the Ministry of Health of the Russian Federation for use in laboratories licensed to conduct this type of laboratory research.

HCV RNA is the earliest marker of viral replication, detected by polymerase chain reaction (PCR) several weeks after infection. An enzyme-linked immunosorbent assay (ELISA) is used to detect anti-HCV. Currently, third generation test systems ELISA-3 are used. The confirmatory method is recombinant immunoblotting (RIBA). In 60% of patients, anti-HCV is detected in the acute phase, in 35% it appears 3-6 months after infection, in 5% of infected individuals anti-HCV is not detected.

The disease may be asymptomatic. The most common symptom is weakness. A targeted survey of patients often helps to identify risk factors such as blood transfusion, intravenous drug administration, chronic hemodialysis, etc. In addition to weakness, the patient may complain of fatigue, heaviness in the right hypochondrium, pain in the right upper quadrant of the abdomen, and dyspeptic symptoms.

The criteria for diagnosis are enlarged liver and spleen, hyperfermentemia and anti-HCV in the blood for at least 6 months.

Hepatosplenomegaly is detected in no more than 50% of patients who seek help; the activity of serum transaminases rarely exceeds the upper limit of normal by 6 times. It should be noted that the activity of serum transaminases does not reflect the degree of changes in the liver: it may be normal, despite significant morphological changes. Serum HCV RNA concentrations are essential for determining infectivity and for monitoring treatment outcomes. If HCV RNA is present in the blood, a liver biopsy usually reveals a number of changes. The concentration of HCV RNA in serum exceeding 105 molecular equivalents (copies) in 1 ml is observed in the active phase of the disease and coincides with peaks of transaminase activity.

The presence or absence of HCV RNA, as a rule, is not a diagnostic criterion for chronic hepatitis C and determines the phase of the process (active, inactive).

For early detection of HCC in patients with liver cirrhosis, especially in men over 40 years of age, serum α-fetoprotein levels are determined every 6 months and liver ultrasound is performed.

Algorithm for the management of HCV-positive patients

Natural history and prognosis

HCV infection leads to the development of acute hepatitis C, which occurs in manifest (icteric) or more often in latent (anicteric) forms, which develop in a ratio of 1:6. About 17-25% of patients with acute hepatitis C recover spontaneously, the remaining 75-83% develop chronic hepatitis C. Most patients with biochemical and immunological signs of chronic hepatitis have a mild or moderate degree of inflammatory-necrotic liver damage and minimally expressed fibrosis. Approximately 26-35% of patients with chronic hepatitis C develop liver fibrosis within 10-40 years and may die from liver cirrhosis and its complications. 30-40% of patients with cirrhosis have a high risk of liver cancer.

It is believed that no more than 30% of patients with HCV with minimal morphological activity may develop liver cirrhosis after 20 years. Thus, patients in whom histological examination of a liver biopsy reveals the presence of minimal inflammation and minimal fibrosis require dynamic monitoring.

If HCV RNA persists for more than 6 months, spontaneous resolution of chronic HCV infection is unlikely.

Clinical picture

Most patients with chronic hepatitis C are asymptomatic. If complaints exist, they are most often weakness, dull pain in the right hypochondrium, nausea, loss of appetite, itching, arthralgia and myalgia. A physical examination of the patient often helps establish the diagnosis only at the stage of liver cirrhosis.

Extrahepatic manifestations of HCV infection

The association of chronic hepatitis C with various extrahepatic manifestations is a fact well known to doctors. The most likely pathogenesis for most diseases and syndromes observed during HCV infection appears to be immune pathogenesis, although the specific mechanisms are largely unclear. Proven and suspected immune mechanisms include:

• mono- or polyclonal proliferation of lymphocytes;
• formation of autoantibodies;
• deposition of immune complexes;
• secretion of cytokines.

The frequency of immune-mediated diseases and syndromes in patients with chronic hepatitis C reaches 23%. Autoimmune manifestations are most typical for patients with the HLA DR4 haplotype, which is associated with extrahepatic manifestations in autoimmune hepatitis. This fact confirms the hypothesis about the trigger role of the virus in the initiation of autoimmune processes in a genetically predisposed individual.

Diseases associated with HCV infection

Associated with the production or deposition of immunoglobulins:

• Cryoglobulinemia
• Leukocytocluster vasculitis
• Membranous proliferative glomerulonephritis
• B cell lymphoma
• Plasmacytoma
• MALTomas

Autoimmune:

• Thyroiditis
• Sjögren's syndrome
• Hemolytic anemia
• Thrombocytopenia
• Lichen planus

Associated with an unknown mechanism:

• Porphyria cutanea tarda

The detection of serum autoantibodies reflects the most common phenomenon of autoimmunization during HCV infection, which is diagnosed in 40-65% of patients. The spectrum of autoantibodies is quite wide and includes ANA (up to 28%), SMA (up to 11%), anti-LKM-1 (up to 7%), antiphospholipid (up to 25%), antithyroid (up to 12.5%), rheumatoid factor, anti-ASGP-R, etc. Most often, the titers of these antibodies do not reach diagnostic values ​​indicative of a particular autoimmune pathology.

Anti-GOR are antibodies specific for HCV infection and are detected in at least 80% of patients. The epitope recognized by anti-GOR is located on an as yet unidentified nuclear protein that is overexpressed in hepatocellular carcinoma. Anti-GOR production is associated only with HCV infection, but not with AIH.

Autoimmune disorders are observed on average in 23% of patients with chronic hepatitis C. The most common pathology of the thyroid gland.

Histological examination of the liver

The histological picture is not pathognomonic, and characteristic changes are often detected. Its distinctive feature is lymphoid aggregates or follicles in the portal tracts, which can be either isolated or part of inflammatory changes in the portal tracts. In terms of cellular composition, these aggregates resemble primary lymphoid follicles in the lymph nodes. Fatty degeneration is detected in 75% of cases. In addition, the following characteristic changes are revealed: non-purulent cholangitis with lymphoid and plasma cell infiltration of the duct walls; lymphohistiocytic infiltration of the periportal zone; mild stepwise necrosis; bridging necrosis (rarely found), proliferation and activation of liver satellite cells, proliferation of the epithelium of bile canaliculi.

It was noted that the histological activity index (HAI) and fibrosis index (IF) in patients with chronic hepatitis C with the presence of fatty degeneration are significantly higher than in patients without concomitant fatty degeneration. In 93% of patients with fatty degeneration, HCV Core protein was detected in hepatocytes, in the absence of fatty degeneration - only in 39%. This fact emphasizes the role of Core protein in the development of fatty degeneration of hepatocytes.

Liver biopsy plays a significant role in clarifying the diagnosis and assessing the activity and stage of the disease.

HCV RNA can be detected in liver tissue using PCR.

Prevention of viral transcription and translation

Treatment

The main goal of treatment is to prevent progression of the disease.

Rest, diet and vitamin intake do not have a therapeutic effect.

Selection of patients for treatment. The indication for interferon therapy is moderate (but not minimal) or severe inflammation and/or fibrosis. The decision to treat patients with liver cirrhosis is made individually in each specific case. Patients in whom histological activity is minimal should be closely monitored, as they have a good life prognosis without treatment and a very low risk of developing cirrhosis after 10-20 years.

Factors associated with the beneficial effect of antiviral therapy in chronic HCV infection:

• Age under 45
• Female
• No obesity
• Duration of infection less than 5 years
• No HBV co-infection
• No immunosuppression
• No alcoholism
• Moderate increase in ALT
• No cirrhosis
• Low iron content in the liver
• Low serum HCV RNA level
• Genotype 2 or 3
• Virus population homogeneity

In patients with normal ALT levels and a positive HCV RNA test without histological examination results, antiviral treatment is not recommended.

The main drug that has been proven effective in treating hepatitis C is interferon alpha (IFα).

Currently, the optimal monotherapy regimen for IF has been adopted: a single dose is 3 million IU, administered subcutaneously or intramuscularly 3 times a week for 3 months. After 3 months, it is necessary to study HCV RNA. If the PCR results are positive, the treatment regimen is changed. If RNA is not detected, treatment is continued for up to 12 months. A persistent positive response in this case is recorded in 15-20% of patients.

The optimal treatment regimen for chronic hepatitis C at present is a combination of IFa and ribavirin.

According to the recommendation of the consensus conference of the European Association for the Study of the Liver (1999), patients with a newly diagnosed chronic hepatitis C and indications for treatment should be prescribed IFa in combination with ribavirin in the following courses:

• for 6 months - for genotypes 2 and 3;
• for 6 months - with genotype 1 and low level of viremia;
• within 12 months - with genotype 1 and a high level of viremia.

A persistent positive response to combined treatment of IFa with ribavirin is observed in 40-60% of cases.

The daily weight of ribavirin is 1000-1200 mg, depending on body weight.

In recent years, to increase the effectiveness of interferon, pegylation has been used, which involves adding polyethylene glycol to the interferon molecule. As a result, PEG interferon is formed, which has a longer half-life. Preliminary data suggest that this treatment is more effective than interferon alpha therapy.

One of the most promising pegylated interferons is Pegasys - PEG interferon alpha-2a, connected to a branched polyethylene glycol molecule, the molecular weight of which is 40 kDa, the total weight of the molecule is about 60 kDa. The characteristics of the chemical structure of this drug determine its pharmacokinetic properties and clinical effectiveness. The polyethylene glycol molecule is attached to interferon alpha through the most stable amide bond, this makes the Pegasys molecule extremely resistant to the action of petidases and allows the drug to be released in the form of a dissolved and ready-to-use dosage form. A feature of the polyethylene glycol molecule is the ability to actively bind several water molecules, which creates a “water cloud” effect around the chemical structural unit of Pegasis, making it stable in the internal environment and giving the drug a relatively small volume of distribution. This, in turn, ensures that there is no need to adjust the dose of the drug depending on the patient’s body weight: Pegasys is administered once a week at a dose of 180 mcg. Significant advantages of the drug Pegasys are significantly better tolerability and a lower frequency of adverse reactions associated with the systemic action of interferon alpha, which significantly improves the quality of life of patients receiving treatment for chronic hepatitis C. In addition, unlike other pegylated interferons, Pegasys does not require significant dose adjustment depending on the functional state of the kidneys, which makes the drug indispensable in patients with concomitant chronic renal failure.

The clinical effectiveness of Pegasis has been assessed by solid large-scale multicenter randomized studies. It has been shown that the rate of proven response to treatment is significantly higher than that of “short” interferons, both in monotherapy regimens and in combination with ribavirin. Particularly impressive in this regard are the results of etiopathogenetic therapy using Pegasys in combination with ribavirin in the so-called “difficult” category of patients with morphological manifestations of liver cirrhosis, 1b genotype of the virus, high viremia: the frequency of proven response to treatment in this category of patients when using Pegasis in combination with ribavirin can be about 40%; in other categories of patients this figure can exceed 75%, which was previously an almost unthinkable result.

Other antiviral drugs in the treatment of chronic hepatitis C

There is evidence of the positive effect of drugs such as rimantadine, ursodeoxycholic acid, pegylated interferons, glycyrrhizic acid preparations, but this information needs further verification.

For questions regarding literature, please contact the editor.

Diagnosis of the disease

Diagnosis of chronic viral hepatitis is based primarily on laboratory methods, since in the early stages the disease is often asymptomatic.

First of all, to confirm the cause of the disease, a blood test for specific markers of viral hepatitis is necessary. These are antigens of the hepatitis B or C virus (viral particles) and antibodies produced by the body in the fight against it. In addition to the qualitative determination (detection) of the antigen, it is also necessary to study the level of viral load (the amount of antigen in a certain volume of blood). This makes it possible to judge the activity of virus reproduction and determine indications for antiviral therapy.

To assess liver function, a biochemical blood test is recommended, which includes determining the level of liver enzymes, bilirubin, protein, protein fractions and other indicators. The doctor gives more specific recommendations based on the individual picture of the course of the disease.

To assess the size and structure of the organ, abdominal ultrasound is recommended: this is the simplest method of visualizing the liver.

To determine the degree of fibrosis, fibroelastography or liver biopsy can be performed - sampling a small amount of liver tissue under ultrasound guidance for further examination under a microscope.

Hepatitis: types, forms and symptoms

The liver is the largest organ in the body, weighing about 1.3 kg. It consists of four lobes of different sizes and shapes and is located in the abdominal cavity on the right below the diaphragm.

The human liver has many functions:

• Detoxification is the filtering of harmful substances from the blood, such as alcohol.
• Accumulation and preservation of nutrients. For example, vitamins A, D, K and B12.
• Synthesis of amino acids - the “building blocks” of proteins.
• Production of digestive enzymes - bile.
• Maintaining optimal blood sugar levels.
• Produces 80 percent of the body's cholesterol.
• Glycogen storage and conversion of glucose to glycogen.
• Hormone production.

Hepatitis is an inflammatory disease that destroys liver cells and impairs its functioning. It can cause liver dysfunction, cirrhosis and cancer of this organ.

Types of hepatitis

Depending on the cause of the disease, there are different types of hepatitis:

1. Infectious (viral) hepatitis:
   Hepatitis A
2. Hepatitis B
3. Hepatitis C
4. Hepatitis D
5. Hepatitis E
6. Hepatitis F
7. Hepatitis G
8. Bacterial hepatitis: with leptospirosis, syphilis.
9. Parasitic hepatitis: with amoebiasis, toxoplasmosis, fascioliasis, opisthorchiasis, schistosomiasis
10. The existence of other as yet unidentified hepatitis viruses is suspected.
11. Toxic hepatitis:
    Alcoholic hepatitis
12. Drug-induced hepatitis
13. Hepatitis developing from poisoning with industrial and plant poisons
14. Autoimmune hepatitis

Most often, the human body is affected by the first three hepatitis viruses: A, B, C.

Forms of hepatitis

There are two main forms of the clinical course of hepatitis: acute and chronic.

The acute form of the course is most typical for hepatitis of a viral nature, as well as for hepatitis caused by poisoning, including strong poisons.

In the acute form of hepatitis, there is a noticeable deterioration in the general condition of the patient, the development of signs of general intoxication of the body and impaired liver function (fever, in some cases the development of jaundice, etc.), as well as an increase in the level of transaminases and total blood bilirubin.

With this form of the disease, favorable prognosis is quite possible. Except for its transformation into chronic. In its acute form, the disease is easily diagnosed and easier to treat. Untreated acute hepatitis easily develops into a chronic form. Sometimes, with severe poisoning (for example, alcohol), the chronic form occurs independently.

The chronic form can develop independently (for example, with chronic poisoning with ethyl alcohol), or continue the development of acute hepatitis (viral hepatitis B, D). The clinical picture of chronic hepatitis is poor; the disease is asymptomatic for a long time. Characterized by a persistent increase in liver size, dull pain in the right hypochondrium, intolerance to fatty foods, etc.

In chronic hepatitis, liver cells are gradually replaced by connective tissue, so in most cases, untreated chronic hepatitis leads to the development of liver cirrhosis. Patients suffering from chronic hepatitis are at high risk of developing primary liver cancer.

Symptoms of hepatitis

Common, but not essential, symptoms of acute hepatitis include:

• Jaundice, the most well-known symptom, occurs when bilirubin, not processed in the liver, enters the bloodstream and gives the skin a characteristic yellowish tint. However, there are often anicteric forms of hepatitis.
• Diarrhea.
• Increased fatigue.
• Loss of appetite and weight.
• Slight increase in temperature.
• Pain in muscles and joints.
• Nausea, vomiting.
• Mild pain or heaviness in the abdomen or right hypochondrium.

If you experience most of these symptoms, consult your doctor immediately.

Symptoms

Damage to liver cells inevitably leads to disruption of their functions. This can manifest itself in the form of several clinical and laboratory syndromes (combinations of symptoms).

Asthenovegetative syndrome:

• lethargy, increased fatigue, weakness;
• sleep disturbance (drowsiness during the day, insomnia at night);
• irritability.

Cytolysis syndrome is a complex of biochemical changes reflecting the destruction of liver cells. In the blood with this syndrome, the level of intracellular enzymes increases: AST, ALT, alkaline phosphatase, gamma-glutamyl transpeptidase (GGTP).

Dyspeptic syndrome:

• pain and heaviness in the right hypochondrium;
• nausea, vomiting;
• stomach ache;
• stool disorders.

Hepatosplenomegaly syndrome is an enlargement of the liver and spleen.

Jaundice syndrome is a yellow discoloration of the skin and mucous membranes. The intensity of its manifestation can vary - from a barely noticeable yellowness of the sclera (the white membrane of the eye) to a clear change in skin color. Jaundice is often accompanied by itchy skin. In addition, with the development of cirrhosis, other changes may appear: edema, abdominal enlargement due to the accumulation of fluid in the abdominal cavity (ascites), varicose veins of the anterior abdominal wall (with the appearance of the so-called head of the jellyfish), and a tendency to bleeding.