Chronic Viral Hepatitis

What is Chronic Viral Hepatitis?

Chronic viral hepatitis is a group of infectious diseases spreading around the world at an alarming rate. This is facilitated by the increase in the share of invasive medical procedures, the significant prevalence of injecting drug addiction, and the increasing relaxedness of people’s sexual behavior, and many other factors. The greatest attention is drawn to viral hepatitis B and C.

In most cases, viral hepatitis B has a better prognosis, but its prevalence worldwide has assumed enormous proportions. The proportion of viral hepatitis C in the incidence is somewhat less, but this cannot be completely sure, because this hepatitis proceeds unnoticed and is not for nothing called a “gentle killer” – liver damage in hepatitis C rapidly progresses in apparently healthy people and often leads to cirrhosis of the liver or even for hepatocellular carcinoma. Therefore, although the official incidence rates of viral hepatitis C are always lower than those of viral hepatitis B, the exact number of patients with viral hepatitis B remains unknown.

Due to the nature of epidemiology, chronic viral hepatitis most often affects young people, many of whom, in the absence of adequate treatment, die by 40–45 years from cirrhosis or liver cancer. Alcohol and the simultaneous infection of several hepatitis viruses and HIV can accelerate the progression of the disease.

Causes of Chronic Viral Hepatitis

By etiology distinguish the following chronic viral hepatitis:
– chronic viral hepatitis B, C, D, G;
– chronic viral hepatitis B and D, C and B and other combinations;
– chronic viral hepatitis of unknown etiology (unverified).

Pathogenesis during Chronic Viral Hepatitis

Two factors are important in the pathogenesis of viral liver damage: viral replication and the immune response. As a result of the replication of the hepatitis B virus (HBV), viral antigens (S, C, E) or virus-induced neo-antigens appear on the cell surface of an infected hepatocyte, which are antigen-targeted targets for effector cells.

The different immune response to the antigens of viruses B, C, D, G in the liver tissue determines the outcome of the infection process from virus infection, acute and chronic active hepatitis to liver cirrhosis and hepatocellular carcinoma.

The statement of autoimmune damage to the liver is based on the detection of antibodies: anti-nuclear, anti-mitochondrial, smooth muscle antibodies. In various hepatitis, the definition of these antibodies is important. Thus, anti-nuclear antibodies are detected in 50-70% of active chronic autoimmune hepatitis and in 40% of cases of primary biliary hepatitis. Anti-nuclear antibodies – one of the indicators that allows to differentiate chronic autoimmune hepatitis from prolonged viral.

Antibodies to smooth muscles – actin belong to the class G and M, most characteristic of autoimmune (80% of cases) – lupoidnogo hepatitis and primary biliary cirrhosis (50%).

Antimitochondrial antibodies are characteristic of patients with primary biliary cirrhosis of the liver (90% of cases) and are found in a certain number of patients with CAH, including viral etiology. The definition of these antibodies is very important in the differential diagnosis of primary and secondary biliary cirrhosis.

In chronic hepatitis, the pathological process develops mainly in the connective tissue. Currently, activation of the liver mesenchymal tissue is considered as the main cause of chronic hepatitis and fibrosis of its parenchyma, followed by the development of liver cirrhosis. Chronization of the process develops as a result of discoordination between connective tissue and epithelial elements as a result of necrosis of the liver parenchyma.

Activated mesenchyme has a damaging effect on hepatocytes, which leads to step necrosis. This explains the self-prog ressirovanie chronic hepatitis. It must be assumed that the progression of the pathological process is aggravated by the autoimmune response of the patient.

Thus, chronic active viral hepatitis is a chronic liver disease caused by exposure to hepatotropic viruses of type B, C, D (delta) and G.

Symptoms of Chronic Viral Hepatitis

The frequent symptoms of chronic viral hepatitis include unmotivated weakness, a feeling of heaviness in the right hypochondrium, and sometimes subfebrile. Unfortunately, these symptoms are non-specific and can occur in many other diseases.

The severity of clinical symptoms depends on the form and duration of chronic hepatitis. In patients with chronic cholestatic hepatitis, the clinic is dominated by cholestasis symptoms — jaundice, itching of the skin, its pigmentation, xanthomas, dyspeptic manifestations, moderate enlargement of the liver, less often the spleen.

Diagnosis of Chronic Viral Hepatitis

Timely diagnosis of chronic viral hepatitis is difficult. Abroad, the average time to establish a diagnosis is 10 years from the moment of infection. More than 70% of patients at the time of diagnosis no symptoms of hepatitis are detected. The rest are possible hepatomegaly, splenomegaly, hepatosplenomegaly, increased levels of bilirubin. In at least 1% of patients, hepatitis is first diagnosed at the stage of cirrhosis.

The reason for examining a patient for viral hepatitis markers may be an unreasonable increase in serum transaminase levels, accidentally detected esophageal veins, as well as epidemiological criteria: close contact with a patient with chronic hepatitis, drug addiction, the presence of hemophilia in a patient, birth of an infected mother of a child, etc.

In some cases, hepatitis may be accompanied by the development of extrahepatic manifestations (autoimmune thyroiditis, glomerulonephritis, lichen planus, cryoglobulinemic syndrome, etc.). At the same time, hepatitis itself may not manifest clinically. Since the listed diseases are polyetiological, if they are present, it is always necessary to remember about the possibility of viral hepatitis in a patient and conduct relevant research.

If suspected of having hepatitis B, patients are tested for the presence of hepatitis B and C markers that can cause chronic liver disease. These are hepatitis B surface antigen (HBsAg), antibodies to the core antigen of the hepatitis B virus (anti-HBc), and antibodies to the hepatitis C virus (anti-HCV). Other markers are used to clarify the diagnosis, determine the indications for treatment, the prospects for curing the patient and should not be used during routine screening.

For the diagnosis of all forms of chronic hepatitis, the most important biochemical indicators, which are most often used to assess the state of the liver, are taken into account. Conditionally, liver enzymes can be divided into four groups.

The first group consists of excretory enzymes: alkaline phosphatase (alkaline phosphatase), lecithin amino peptidase (PAH), gamma-glutamyl transpeptidase (GGT). The study of the activity of these enzymes allows you to judge the damage to the liver parenchyma and the presence of cholestasis. Morphological changes in the bile duct are accompanied by an increase in the level of alkaline phosphatase, LAP, GGT, which may indicate the presence of infiltrative lesions. With toxic damage caused by alcohol, drugs, radiation, chemicals, the level of GGT increases, which indicates the stimulation of the activity of microsome enzymes.

The second group consists of secretory enzymes: serum cholinesterase (CE), lactate dehydrogenase (LDH), in particular LDH-4 and 5.

The third group consists of indicator enzymes, which are divided into:
• cytoplasmic (alanine aminotransferase (AlAT));
• mitochondrial (LDH-4,5; aspartate aminotransferase (AcAT).

The fourth group consists of the enzymes of the ornithine cycle: arginase and ornithine decarboxylase, the decrease in the activity level of which reflects the depression of the neutralizing function of the liver. A decrease in the activity of ornithine decarboxylase in the blood to a certain extent indicates a decrease in the synthetic function of the hepatocyte, since the enzyme initiates the production of extremely important biologically active substances of polyamines, in particular spermine, one of whose functions is the ability to intensify protein-synthetic processes in the hepatic cell.

Treatment of Chronic Viral Hepatitis

Hospitalization of patients with chronic hepatitis of established and unknown etiology, including patients with cirrhosis of the liver, should be carried out in infectious hospitals.

Disease therapy should take into account the degree of activity of the pathological process, the leading syndrome of the disease, the presence of signs of the cirrhotic stage and the phase of viral infection (integration or replication).

Treatment of hepatitis viral etiology in the first place should begin with measures to normalize the mode of work and rest (exclusion of work at night, business trips, overwork and stress, etc.). General measures suggest the elimination of harmful xenobiotics (alcohol, chemicals, hepatotoxic drugs – tetracycline, nonsteroidal anti-inflammatory drugs, tranquilizers).

Important is the appointment of a diet. The diet should be complete, nutritional restrictions are justified only if other organs of the digestive system are affected. When prescribing a diet, it is necessary to take into account the habits of the patient, the portability of food. From the diet should be excluded foods that have a choleretic effect (fried, spicy, spicy, smoked dishes), products containing refractory fats, food dyes, preservatives.

According to the testimony for the normalization of digestion, you can assign enzyme preparations that do not contain bile (mezim, pangrol, in some cases it is advisable to use Ursofalk). If the patient is worried about asthenia, it is possible to assign adaptogens, such as tinctures of Eleutherococcus, Schisandra, and dipper.

Currently, interferon-α, nucleoside analogues (lamivudine, adefovir, entecavir), pegylated interferon α-2a (Pegasys) are used to treat viral hepatitis B in the world. Interferon-α, lamivudine and Pegasys are on the Ukrainian market.

The disadvantages of simple interferon-α are the low frequency of responses to treatment, as well as some inconvenience of use. Nucleoside analogs also have several disadvantages: their effect is manifested only during their use, and discontinuation of the drug causes reactivation of the viral infection and relapse of the activity of hepatitis. On the other hand, long-term therapy with lamivudine can lead to the formation of viral resistance due to the development of YMDD mutations (mutations in the YMDD portion of the DNA polymerase molecule of the virus), which also contributes to the reactivation of the virus and the development of relapse. The risk of such mutations increases steadily with an increase in the duration of treatment with lamivudine, and the lack of clear criteria for the required duration of therapy with lamivudine leads to significant limitations in its use in the treatment of viral hepatitis B.

All these problems stimulated the search for a more effective and convenient drug. The solution to this complex problem was found by creating pegylated interferons. Pegasis is the first and for today the only pegylated interferon in the world approved for the treatment of viral hepatitis B. This drug provides a longer remission compared to other therapy regimens, and the drug is effective in both HBeAg-positive and HBV-negative patients and can be used as monotherapy. Pegasys provides the highest frequency of HBeAg seroconversion, suppression of hepatitis B virus DNA, normalization of AlAT level, HbsAg seroconversion, and in general, the effectiveness of the drug is higher than in the treatment with simple interferon and lamivudine. Pegasis therapy does not lead to the formation of virus resistance and is well tolerated by patients.

The efficacy and safety of Pegasys has been proven in multicenter international studies, on the basis of which the National Institutes of Health (United Kingdom) recommended Pegasys as a first-line treatment for viral hepatitis B.

Basic therapy

  1. Diet – table number 5 with individual modifications, a complex of vitamins, especially C, P, E, B6, as well as others in reasonable therapeutic doses, mineral water.
  2. Means normalizing the activity of the gastrointestinal tract, preventing dysbiosis, accumulation of intestinal endotoxins, endotoxinemia. These include eubiotics (lactobacterin, bifidumbacterin, colibacterin, and the like). It is advisable to take baktisubtil, enterol-250, lactulose, if necessary – enzymes (pancreatin, festal and the like), intestinal antiseptics or poorly absorbed antibiotics.
  3. Hepatoprotectors possessing certain metabolic properties, and some of them are also anabolics: Riboxin, Cytochrome C, Thioctacid, Heptral, Hepargens, Syrepar, Flavanoids (Silibor, Kars, Legal, Catergen), Liv-52, Hepatyl, Essentiale and others
  4. Medicinal herbs with antiviral (St. John’s wort, licorice, calendula, celandine, etc.), mild choleretic and mainly antispasmodic effect (milk Thistle, mint, knotweed, etc.).
  5. Physiotherapy activities, physiotherapy.
  6. Psychological (psychotherapy, hypnosis, etc.), social and professional aspects of therapy and rehabilitation (release from severe physical exertion, psychoemotional and social support).
  7. Treatment of associated diseases and conditions, symptomatic agents.

Syndromic therapy, including special treatment methods
The cytolytic syndrome detected in chronic hepatitis requires correction by administering protein preparations (albumin), coagulation factors (plasma, cryoprecipitate), exchange transfusion of freshly preparinized blood, perfusion of blood through heteroprotein, extracorp methods of oral detoxification, etc.

Cholestatic syndrome is controlled by administration of enterosorbents (cholestyramine, bilignin, carbol, polyphepan, waulen), and, as shown in recent years, preparations of unsaturated fatty acids (ursofalk, henofalk and the like), hemo-, plasmasorbtion.

Autoimmune syndrome requires the appointment of immunosoriented therapy: azathioprim (imuran), delagil, corticosteroids, plasma sorption, systemic enzymes (wobenzym).

In chronic hepatitis with bacterial overlay, the prescription of antimicrobial agents (trichopol, ampicillin, augmentin, etc.) is indicated.

Describing the main directions of treatment of chronic viral hepatitis, it should be noted the feasibility of complex therapy, including combination antiviral therapy, including interferons, against the background of basic and syndromic therapy.
The criterion for the appointment of antiviral drugs is the phase of replication.

Etiotropic (antiviral) therapy
The following drugs are used.
Synthetic nucleosides (reverse transcriptase inhibitors):
– azidothymidine (retrovir) – 600-800 mg / day, etc .;
– lamivudine (epivir, 3TC) – 300-600 mg / day;
– ribavirin (synthetic nucleoside) from 1 to 2 g / day.

Protease inhibitors:
– Crixivan at a dose of 600 mg / day, etc.

Options for the specific treatment of chronic hepatitis B can be an immunoglobulin with a high titer of anti-HBs and anti-hepatitis gene-engineering vaccine.

In medical practice, the most widely used genetically engineered recombinant a-interferons (IFN-a). The most pronounced antiviral effects have IFN A-2b (Intron A, Realdiron, Viferon). IFN a-2a preparations are also used (Reaferon, Roferon A, etc.). With the prolonged appointment of recombinant IFN, when a large amount of IFN-neutralizing antibodies are formed in the patient’s body, natural (natural) IFN is used – Alfaferon, Welferon, Egiferon.

The drugs are used mainly in course doses of 3-6 million IU subcutaneously or intramuscularly 3 times a week for a duration of 3 to 12 months.

In chronic unverified viral hepatitis, indications for the prescription of IFN may be the activity of ALT, as an indicator of exacerbation of the disease, in conjunction with clinical data.

In immuno-oriented treatment of chronic hepatitis, carried out under the supervision of an immunologist, interferon inducers (cycloferon, amixin, etc.), interleukins (IL-1, IL-2), preparations of the thiopoietin group (Glutoxim, molixan, etc.) are used.

Clinical supervision is carried out for life in the offices of infectious diseases or specialized hepatological centers.