Chronic viral hepatitis c. How long can people live with hepatitis C if left untreated?

1 Department of Hepatology and Gastroenterology, Hopital Henri Mondor, AP-HP, Universite Paris-Est, INSERM U955, Creteil, France; 2 Department of Hepatology and Gastroenterology, Center Hospitalier Universitaire de Nancy, Universite de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France

E— mail: [email protected](C. Hezode).

Essay

Modern all-oral interferon-free regimens achieve sustained virological response (SVR) in 90% of cases and can reduce treatment duration to 12 weeks. in most patients with chronic hepatitis C, including patients with and without cirrhosis, previously untreated and already treated. There are many combinations of direct acting antiviral drugs (DAAs) that can be used to achieve an optimal balance between the effectiveness and safety of therapy. Each of these regimens can be modified in various ways, including the use of ribavirin (RBV). When using sofosbuvir-based combinations (SOF), the use of RBV is appropriate in the following situations: in patients infected with hepatitis C virus (HCV) genotype 1, previously treated and with cirrhosis or decompensated cirrhosis, and in patients infected with HCV genotype 3, with cirrhosis of the liver. In these situations, the addition of RBV can reduce the duration of treatment to 12 weeks. in most cases, which leads to a decrease in its value. The need to use RBV in patients with cirrhosis treated with SOF and simeprevir remains to be determined. RBV is recommended for the treatment of all patients infected with HCV genotype 1a receiving a combination of three DAAs: paritaprevir/ritonavir, ombitasvir, dasabuvir. In general, adding RBV to various DAA combinations slightly increases the risk of anemia. However, severe anemia is rare and responds well to RBV dose reduction without affecting SVR.

Practically due to the fact that RBV is inexpensive drug, which is well tolerated when combined with interferon-free regimens, it remains effective means to improve hepatitis C treatment regimens and optimize the results of their use.

© 2015 European Association for the Study of the Liver.

Keywords: ribavirin, direct-acting antivirals, without interferon, sofosbuvir.

Retrieved February 22, 2015; received with amendments September 9, 2015; accepted for publication September 15, 2015

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As a result of genome variability within one genotype, a large number of mutant, genetically different variants of HCV quasispecies viruses circulating in the host body are formed. It is with the presence of quasispecies that the escape of the virus from the immune response, long-term persistence of HCV in the body, the formation of hCG, and resistance to interferons are associated.

Over the past 5 years, chronic viral hepatitis C has taken first place in terms of incidence and severity of complications. In the structure of the incidence of chronic viral hepatitis in the countries of Western Europe, HCV infection accounts for 60-80% of cases.

Treatment and outcome of hepatitis C virus infection (elimination or persistence of the virus), the presence and severity of liver damage, other

organs and systems are determined by the relationship between virus factors: the amount of infected material, the spectrum of infected cells, the ability of the virus to mutate, the severity of the cytopathic effect) and host factors.

The progression of CHC is determined by many factors (the nature of the virus, co-infection with HBV and HIV, alcohol abuse, drug addiction, age of the patient). Factors of the virus include its genotype, the degree of heterogeneity of the population (quasispecies), and the volume of infected material. Despite the availability of data on the influence of HCV genotype on the course and prognosis of chronic hepatitis C, their results are contradictory. Considering the established connection of HCV genotypes with various routes of infection (mainly the spread of lb during blood transfusions, 1a, 2a, 3 - among drug addicts), it is assumed that the severe course of the disease caused by HCV lb infection may be due to the influence of additional factors - infection during blood transfusions (large volume of infected material). It is assumed that this volume determines the severity of initial liver damage and the course of HCV infection.

HCV infection leads to the development of acute hepatitis C, occurring in a manifest (icteric) or more often in a latent (anicteric) form, occurring in a ratio of 1: 6. About 17-25% of patients with acute hepatitis C recover spontaneously, 75-83% develop chronic hepatitis C. Approximately 26-35% of patients with chronic hepatitis C develop liver fibrosis within 10-40 years with the formation of cirrhosis. In 30-40% of patients with liver cirrhosis, liver cancer may develop.

The HCV-specific humoral immune response is characterized by the formation of antibodies directed against structural as well as non-structural antigens of HCV. There is no specific antibody response during HCV infection. The possibility of re-infection with HCV not only by other, but also by homologous strains has been proven.

The HCV-specific cellular and humoral immune response is polyclonal and multispecific. The leading role in the immunopathogenesis of CHC is played by the insufficiency and qualitative features of the CD4+ T-helper (Tx) response in the early stages of infection. Activation of CD4+ T helper cells requires their recognition of viral antigens presented by molecules of the major histocompatibility complex (HLA) class II on the surface of antigen-presenting cells (macrophages, dendritic cells, B-lymphocytes). Txi are stimulators of the cellular response and secrete pro-inflammatory cytokines (interferon, interleukin-2, tumor necrosis factors and enhancing cytotoxic reactions, have a direct cytotoxic effect on transformed cells, induce cytotoxicity of normal macrophages. Th2 are stimulators of the humoral response and produce a number of interleukins that have an anti-inflammatory effect (interleukins-4 and -10) by suppressing the action of interferon-y.

There is a direct dependence of activity on the duration of the disease at various stages of chronic HCV infection.

The most important feature of HCV infection is the ability of the virus to persist for a long time in the human body. Despite the presence of a virus-specific immune response, it does not protect against reinfection. All factors have not yet been identified

interactions between the virus and the host that cause the immune response to control the infection. Data about biological properties HCV and the frequency of chronicity (up to 85%) indicate the decisive role of viral factors aimed at modulating the host immune response

In the early stages of infection, suppression of the induction of the immune response plays a crucial role. The virus is able to influence the process of CD4+ Tx activation by disrupting the interaction of antigen-presenting cells and T-lymphocytes.

In the process of chronic HCV infection, mechanisms for suppressing the implementation of the immune response are important, among which the most important role is played by the virus avoiding the humoral and cellular immune response through mutation. Mutation of HCV epitopes, which are targets of cytotoxic T lymphocytes, leads to disturbances in antigen processing and epitope recognition, and antagonistic relationships between CTLs. The lack of an effective T-cell immune response is due to the low level of HCV replication observed in almost 100% of hepatocytes, which causes low expression of HLA and other immunoinflammatory molecules on the surface of infected cells.

The outcome and course of the process is greatly influenced by the amount of infected material. The impact of the genotype and degree of heterogeneity of the HCV population on the course of infection has not yet been proven. The role of immunogenetic factors in the development of HCV infection has been revealed (HLA class II genotype determines the outcome of acute HCV infection; heterozygosity for the hemochromatosis gene correlates with the degree of fibrosis; heterozygosity for the PiMZ phenotype of al-antitrypsin deficiency and genetic factors that determine susceptibility to fibrosis).

Among the host factors influencing the outcome and course of HCV infection, the importance of age at the time of infection, alcohol abuse, co-infection with hepatotropic viruses, lipid metabolism disorders, etc. has been studied.

Damage to HCV-infected hepatocytes includes:

• The direct cytopathic effect of the virus is the effect of virion components or virus-specific products on cell membranes and hepatocyte structures. The HCV core protein has been shown to be involved in a number of cellular processes. It is capable of modulating the transcription and translation of some cellular genes and causing phenotypic changes in hepatocytes.
• Immune-mediated damage directed at intracellular HCV antigens, which is either a direct interaction of a cytotoxic T lymphocyte with a target cell (cytotoxic reaction, resulting in colloid-osmotic lysis of the target cell) or mediated by cytokines. Activated CD4 and CDS lymphocytes were detected in the portal tracts and inside the lobules, as well as the expression of HLA class I and II molecules and adhesion molecules on the surface of hepatocytes and bile duct cells. There is no direct correlation between the level of viremia, HCV RNA in the liver, as well as the expression of virus antigens in liver tissue and the activity of the liver process (laboratory and histological). Patients with a more active T-cell immune response to HCV infection have a more low level viremia, higher activity of the liver process. The immune reaction to viral antigens carried out by T lymphocytes is the main cause of apoptosis, which is considered as one of the main mechanisms of damage to hepatocytes during HCV infection.
• Virus-induced autoimmune mechanism of damage. The involvement of autoimmune mechanisms in liver damage has been proven based on the high frequency of detection of serological markers of autoimmunity. In approximately 1/3 of patients, non-organ-specific autoantibodies are detected.

We can talk about spontaneous recovery from hepatitis C in cases where the patient, without receiving specific therapy, feels well, there is normalization of biochemical blood parameters, there is no increase in the size of the liver and spleen, and there is no HCV RNA in the blood for at least 2 years after acute hepatitis WITH.

Symptoms of Chronic viral hepatitis C

Features of clinical manifestations. Chronic viral hepatitis C occurs, as a rule, with a poor clinical picture and transient levels of transaminases.

The disease often occurs subclinically; its distinctive feature is a torpid, latent, asymptomatic course, often unrecognized for a long time. CHCV develops 6 months after suffering, often in a latent form, acute viral hepatitis C. Weakness and increased fatigue may be experienced periodically. In the latent phase, an objective examination reveals a slight enlargement of the liver with a dense consistency, rusemia with a complete or almost complete absence of clinical manifestations. During the replicative phase clinical picture characteristic Mainly asthenovegetative symptoms, decreased pettitis, and the presence of hepatolienal syndrome. Possible weight loss and repeated fever. The course of the disease is undulating. The disease is characterized by a successive change of acute, latent and reactivation phases, liver cirrhosis and hepatocytosis. lular carcinoma.

In the acute phase, complete elimination of the virus and recovery are possible in 10-15%, despite the reduced activity of cellular and humoral immunity factors. The acute phase of chronic hepatitis C is often characterized by a wave-like course with a repeated increase in body temperature to subfebrile levels and peaks of increased ALT activity, as well as the presence of HCV RNA and HCVAb IgM in the blood. Periods of exacerbation are followed by phases of remission.

The latent phase is characterized by the failure of immunocompetent mechanisms to eliminate the virus. However, the immune system is partially capable of supporting protective mechanisms, as a result of which, while maintaining weakly active reproduction of the virus clinical manifestations there are no diseases. The latent phase is more often registered in women as “chronic virus carriage.” An objective examination reveals a slight enlargement of the liver, which has a dense consistency. Some patients experience periodic increases in ALT activity. A morphological examination of liver tissue reveals signs of lobular hepatitis. The presence of HCV RNA in the blood does not necessarily indicate viral replication, since pathological changes in the liver tissue may be absent or minimal. The presence of the virus in the blood in the absence of histological changes in the biopsy specimen suggests infection with non-virulent strains of the virus, the body's tolerance to HCV, as well as possible extrahepatic replication of the virus. When “carrying the virus,” genotype 3a is more often detected and genotype lb is less often detected.

During the reactive phase, immunocompetent cells completely lose their functional activity and protective function, which leads to the progression of the infectious process. This phase usually develops many years after infection and marks the beginning of the manifest course of chronic viral hepatitis C.

The clinical picture is characterized mainly by the presence of asthenovegetative symptoms (weakness, decreased ability to work), decreased appetite, and the presence of hepatolienal syndrome. Possible loss of body weight, repeated increase in body temperature to subfebrile levels. The possibility of developing extrahepatic (systemic) manifestations is noteworthy. A connection with chronic HCV infection has been proven for such extrahepatic manifestations as severe cryoglobulinemia, membranous proliferative glomerudonephritis, and porphyria cutanea tarda. A possible association between HCV infection and idiopathic thrombocytopenia, lichen planus, Sjogren's syndrome and B-cell lymphoma is considered. Among the clinical manifestations of cryoglobulinemia, it is necessary to note weakness, arthralgia, purpura, peripheral polyneuropathy, Raynaud's syndrome, arterial hypertension, and kidney damage. Among the endocrine pathologies, hypothyroidism, hyperthyroidism, and Hashimoto's thyroiditis prevail. Damage to the organ of vision is manifested by ulcerative keratitis and uveitis. A variety of skin lesions have been described in association with chronic hepatitis C, of ​​which cutaneous necrotizing vasculitis with papular or petechial rashes caused by cryoglobulin deposition is most clearly associated with viral infection. Neuromuscular and articular extrahepatic manifestations of chronic viral hepatitis C are in most cases caused by cryoglobulinemia. Muscle weakness, myopathic syndrome, myalgia, myasthenia gravis may be observed. In chronic hepatitis C, unlike hepatitis B, integrative forms are not registered.

Mechanism of hepatic lesions. With HCV infection, a wide range of extrahepatic lesions are observed, conditionally divided into three main groups: extrahepatic lesions of immunocomplex origin (vasculitis of various localizations; cutaneous vasculitis, Raynaud's syndrome, glomerulonephritis, peripheral neuropathy, periarteritis nodosa, etc.); extrahepatic changes of immunocellular and immunocomplex genesis (arthritis, polymyositis, Segren's syndrome, fibrosing alveolitis, etc.); damage to the blood system, including B-cell malignant lymphoproliferation. It is believed that HCV lymphotropy (replication in blood cells, mainly in B lymphocytes) causes chronic stimulation of B lymphocytes and, as a consequence, their activation, increased production of immunoglobulins (various autoantibodies, poly- and monoclonal IgM with rheumatoid factor activity) with the formation immune complexes, including mixed cryoglobulins.

In the development of extrahepatic lesions, the role of possible replication of HCV in various organs and tissues (in addition to the liver and hematopoietic system) with the development of cytotoxic T-cell reactions aimed at virus antigens, autoantigens formed as a result of the direct damaging effect of the virus at the cellular level, is also discussed.

The reactivity phase successively progresses to liver cirrhosis and hepatocellular carcinoma.

Diagnosis of Chronic viral hepatitis C

Features of diagnostics. For the diagnosis of B HS, it is necessary to take into account epidemiological data indicating blood transfusions, surgical interventions, hemodialysis, drug addiction, etc., as well as nonspecific clinical manifestations of the disease (weakness, increased fatigue, slight enlargement of the liver, etc.).

According to the 2000 American Consensus Hepatitis C criteria, optimal approaches for diagnosing and monitoring the disease have now been developed. There are various methods for diagnosing and monitoring HCV infection. Tests that detect antibodies to the virus include the ELISA method, which includes kits containing HCV antigens from non-structural genes, and recombinant immunoblotting methods (RIBA). The same antigens are used in ELISA and RIBA. Targeted amplification tests, including polymerase chain reaction (PCR) or transcription-mediated amplification (TOA), are designed to detect HCV RNA. A biopsy can provide histological characterization of liver damage, but does not diagnose HCV infection.

Serological methods for diagnosing HCV infection. ELISA methods are reproducible, inexpensive, and FDA approved for the diagnosis of HCV infection. They are suitable for screening groups of 0iska and are recommended as tests primary diagnosis for patients with clinical signs of liver disease. The high sensitivity and specificity of third-generation ELISA methods (sensitivity above 99%, specificity 99%) made it possible to abandon the need for confirmatory tests when making a diagnosis in individuals at risk. Negative ELISA results are sufficient to exclude the diagnosis of HCV infection in immunocompetent individuals. Rarely, false negative results occur in immunocompromised patients and individuals on hemodialysis. On the other hand, false-positive ELISA results have been reported in patients with autoimmune disorders, suggesting the need for HCV RNA detection. RIBA remains a useful complementary method for mass screening of blood products.

Qualitative methods for determining HCV. In patients with positive ELISA results, the presence of persistent HCV infection must be confirmed by qualitative determination of HCV RNA. The automated FDA-approved method has a detection limit of 50 IU/mL. Recently, a new transcription-mediated amplification method with a detection limit comparable to PCR has been developed. The test still requires FDA approval to use. The specificity of the methods is 98%. The presence of a single positive result for detecting HCV RNA confirms active replication of the virus; a negative result does not indicate the absence of viremia in the patient. Subsequent qualitative determination of HCV RNA is required to confirm the absence of active HCV replication. In the presence of chronic HCV infection, repeat PCR testing does not make sense in patients not receiving treatment. Almost all patients remain viremic; a negative result may reflect a transient decrease in virus titers relative to the sensitivity threshold of the method.

Quantitative methods for determining HCV. To confirm the diagnosis in a laboratory, it is necessary to examine the blood using ELISA for the presence of antibodies to HCV and ALT activity. Antibodies to HCV can be found not only in the blood, but also be part of circulating immune complexes. However, the results of only one-time studies, taking into account the “window” phase, should not be considered as final. Dynamic monitoring of ALT activity is required at least 1-2 times a month. If ALT activity remains normal for many months in the presence of anti-HCV, then such patients are interpreted as carriers of the HCV virus.

Laboratory diagnosis of hepatitis C is based on identifying specific markers of HCV infection. To diagnose CHCV, you can use the determination of HCV replication activity, as evidenced by the presence of HCV RNA PCR, HCVAb IgM, the spectrum of structural and non-structural antibodies in the immunoblotting reaction, clarification of the HCV genotype, assessment of viremia using the quantitative determination of HCV RNA. It must be remembered that HCV RNA may not be a diagnostic criterion for chronic hepatitis C and at the same time determine the phase of the process (active, inactive). The diagnosis of chronic infection is based on the detection of HCV RNA in the blood by qualitative or quantitative tests for at least 6 months. Prospective studies have found that the majority of individuals infected with HCV develop chronic form infections. Factors associated with spontaneous clearance of the virus include young age, female gender, and certain combinations of major histocompatibility complex genes. Identification is carried out using diagnostic drugs from domestic or foreign manufacturers that have state permission.

The results of the studies can be interpreted as “positive”, “negative” and “uncertain”. If the result is “uncertain”, after 2 months or more, an additional study should be carried out for the presence of markers of HCV infection. PCR can be used as a confirmatory method to detect HCV RNA (provided that approved diagnostic tools are used). government agencies healthcare). Detection of HCV RNA in serum and HCVAb indicates current infection. The absence of HCV RNA in HCVAb-positive blood samples cannot be used. To distinguish between a past HS and a “false-positive” laboratory test result. In addition, some individuals experience unstable viremia, which may determine a “negative” result of HCV RNA detection.

Diagnosis of hepatitis C in the latent phase based exclusively on the indication of HCV markers.

A puncture biopsy of the liver is of great diagnostic importance, with the help of which one can not only assess the activity of inflammation, but also determine the severity of fibrosis. The following morphological manifestations are characteristic of chronic viral hepatitis C: a combination of fatty and hydropic degeneration - Councilman's acidophilic bodies; stepwise necrosis; lymphoid infiltration with the formation of follicles in the portal tracts and intralobularly; chains of lymphocytes in sinusoids; damage to the bile ducts, proliferation of bile ducts (see Fig. XIII color insert). The severity of inflammatory activity at the stage of fibrosis or the presence of already formed cirrhosis of the liver can predict the response to interferon therapy. According to the degree of activity, inflammation is assessed as minimal, minor, moderate and severe. The same 4 degrees are distinguished when assessing the stage of fibrosis (minimal, minor, moderate and severe). The rapid transition of CHCV to liver cirrhosis is indicated by intralobular group necrosis, bridging necrosis, and active septa. Criteria for diagnosis are enlarged liver and spleen, hyperenzyme.

IN last years In the literature, reports appeared on viral genotypes F, G, TTV, which have not yet received universal recognition by the International Committee on Taxonomy and Nomenclature of Viruses. Hepatitis G virus (HGV, GBV-C) contains RNA and belongs to the flavivirus family. The genome of the pathogen consists of structural (E1, E2) and non-structural (NS2, NS3, NS4, NS5) regions encoding the corresponding proteins, the functions of which are similar to HCV. A feature of the virus is the presence of a defective core protein or its complete absence. There is an assumption that there are three genotypes and several subtypes of the virus. Infection occurs through blood transfusion, parenteral interventions, sexual contact, and vertical transmission from mother to child is possible. A combination of HCV/HGV infection is often observed, when the process progresses up to the development of cirrhosis. Chronic hepatitis G is characterized by a benign course with minimal activity. The presence of an active virus in some cases is manifested by an increase in alkaline phosphatase activity. Morphological changes in the liver resemble those seen in chronic hepatitis C.

Treatment of Chronic viral hepatitis C

Features of the treatment of chronic viral hepatitis C. All patients with chronic hepatitis C are potential candidates for antiviral therapy. Treatment is recommended for patients at increased risk of disease progression to cirrhosis. In the European Association for the Study of Liver (EASL) and National Institutes of Health (NIH) guidelines, the indication for etiopathogenetic therapy is moderate to severe necrotizing inflammation and/or fibrosis of the liver with detectable levels of HCV DNA in the blood serum. These individuals are characterized by the presence of a histological picture of portal or interlobular fibrosis or low-grade inflammation and necrosis, and elevated ALT levels. In some patients, the risk factors and the degree of effectiveness of the therapy are not entirely clear, which requires additional research.

The goal of therapy for chronic hepatitis C is eradication of the virus, slowing the progression of the disease, improving the histological picture of the liver, reducing the risk of developing HCC and improving health-related quality of life.

Many of the patients are not included in the study due to drug use, alcoholism, age, and concomitant somatic and neuropsychiatric diseases. Efforts must be made to treat these populations. Since a large number of HCV-infected persons are in prison, a special approach is required for their prevention, diagnosis and treatment.

Treatment of patients should be carried out in centers that ensure compliance with sanitary and epidemiological regulations, by hepatologist specialists (infectious disease specialists and gastroenterologists). If patients have severe concomitant diseases caused by HCV, treatment should be carried out by hepatologists together with specialists according to the profile of the disease.

For etiopathogenetic therapy, antiviral drugs (interferons, cytokines), immunosuppressants (prednisolone, azathiaprine) and combination drugs (IFN + cytokines, or + ribavirin, or + interferon inducers), as well as, according to indications, other pathogenetic agents are used.

In the treatment of chronic viral hepatitis C, interferon is used in the phase of viral replication. The effects of IFN are due to the suppression of virus production and their elimination, immunomodulatory effect, increased expression of HLA antigens on cell membranes, increased cytotoxicity of T cells and natural killer cells, inhibition of fibrogenesis processes, and reduced risk of developing hepatocellular carcinoma. For the treatment of chronic hepatitis C, the following IFNs have been proposed: IFN-aga (reaferon, roferon A, etc.), IFN-aga (intron A, realdiron, etc.), lymphoblastic IFN-a, etc. Recently, the relatively recently created IFN prolonged actions (PegIntron, Pegasys), which can be administered subcutaneously once a week.

A positive effect from the use of interferons is observed with the following clinical and virological data:

• low level of aminotransferase activity in blood serum (increase no more than 3 times compared to normal);
• low level of HCV RNA in blood serum;
• portal or graded fibrosis of the liver in combination with moderate signs of inflammation and necrosis.
• absence of liver cirrhosis or its minimal severity;
• absence of cholestasis;
• normal iron levels in blood serum and liver tissue;
• short duration of HCV infection;
• HCV genotypes 2 and 3;
• infection with a homogeneous viral population, absence of HCV mutants;
• the patient's age is less than 45 years.

Interferons (roferon A, intron A, reaferon) are administered on average 3 million IU 3 times a week (every other day) subcutaneously or intramuscularly for 12 months, provided that HCV RNA disappears after 3 months from the start of treatment. If HCV RNA is detected after 3 months, it is not advisable to continue therapy according to the specified regimen. JAccording to the recommendations of the Russian consensus of 2000, the basis for IFN monotherapy is:

• young age at the time of infection (up to 40 years);
• female;
• lack of excess body weight;
• absence of elevated iron levels and increased GGTP activity in the blood serum;
• elevated ALT level;
• the presence of a moderate degree of process activity and minimal fibrosis in the liver;
• low level of HCV RNA and not 1 genotype of hepatitis C virus

The absence of these factors can be considered as an indication for combination therapy.

Favorable factors for interferon therapy are also the duration of the disease no more than 5 years, the absence of histological signs of liver cirrhosis, the absence of alcoholism (normal level of antihypertensive drugs), drug addiction, the absence of co-infection with HBV and HIV, advanced level ALT in the presence of HCV RNA in the serum.

Unfavorable factors affecting the effectiveness of inferon therapy are the duration of the disease over 5 years, elderly age patient, pronounced histological changes in the liver punctate.

Contraindications to interferon therapy:

Absolute:

• severe depression or a history of depression;
• uncontrolled epilepsy or seizure disorder;
• thrombocytopenia (less than 50,000 cells in 1 μl), leukopenia (less than 1500 cells);
• organ transplantation (except liver);
• the presence of decompiled liver cirrhosis;
• severe heart disease.

Relative:

• severe concomitant diseases of the lungs, kidneys, cardiovascular system, decompensated diabetes;
• uncorrectable thyroid diseases;
• alcohol abuse;
• mental illness, including a history;
• autoimmune hepatitis and severe virus-induced immune disorders;
• concomitant autoimmune diseases;
• AIDS;
• addiction;
• malignant tumors;
• the presence of autoantibodies to mitochondria and other cellular and subcellular structures.

The criteria for the effectiveness of treatment are the normalization of the disappearance of HCV replication phase markers (HCV RNA, HCVAb IgM).

Level of aminotransferases, histological picture of the liver. The rate of positive response to treatment is 40-50%.

Thus, determining the clinical effectiveness of therapy includes assessing the early response to its implementation, as well as the results of treatment immediately after its completion and for a sufficiently long period of time thereafter. When assessing the effectiveness of therapy, the following recommendations should be followed:

• Early virological response is determined by calculating the percentage of patients with a negative qualitative HCV-RNA test result 12 weeks after the start of antiviral therapy.
• The primary response is defined as the percentage of patients with a negative qualitative test result for HCV-RNA and normalization of ALT immediately after completion of the course of antiviral therapy.
• Sustained virological response (sustained biochemical and virological remission) is defined as the percentage of patients with a negative result of a qualitative analysis for HCV-RNA and normalization of ALT 24 weeks after completion of therapy.

The effectiveness of interferons in chronic viral hepatitis C is increased by the combined use of ribavirin at a dose of 800-1200 mg, ursodeoxycholic acid at a dose of 600 mg/day, and essential phospholipids. For interferon-resistant HCV lb hepatitis, interferon-a is administered for the first 6 months at a dose of 6 million IU three times a week. Stable remission is observed in 35-40% of cases. For patients with partial remission, a repeat course lasting up to 1.5-2 years is indicated.

According to the recommendations of the conference on the management of patients with hepatitis C, held in Paris in February 2002, patients with HCV genotype 1 should continue treatment for 48 weeks, provided that after 12 weeks of treatment the virus is undetectable or its titer has decreased by more than 2 lg copies. If there is no effect of treatment, the purpose of which was to eradicate the virus, it may be discontinued. To reduce the rate of development of the disease, it is possible to continue the course. Patients with genotypes 2 and 3 are shown the usual course of combination therapy (IFN + RBV) for 24 weeks. For genotypes 4, 5, 6, a treatment period of up to 48 weeks is recommended, taking into account the risk-benefit ratio of the therapy, assessed individually.

The effectiveness of the use of pegylated interferons is confirmed by the fact that when PegIntron was administered once a week (in all Lozas), an immediate and sustained virological response was observed much more often than when using intron A. At the same time, virological effectiveness at the end of treatment with PegIntron depends on the dose. Use of the drug at a dose of 1.5 mcg/kg once a week increases the rate of sustained virological response by 2 times.

Administration of PegIntron once a week is more effective than monotherapy with introintestinal A. In patients who responded to treatment, a significant improvement in the histological picture of the liver was detected compared with patients in whom there was no effect. A decrease in the degree of fibrosis can be observed in patients with F3/F4 stages of the disease.

Thus, the development of pegylated forms of IFN with improved pharmacokinetics, higher efficiency compared to standard interferons and a more convenient dosage regimen (once a week) provided patients with a higher chance of cure. The use of pegylated interferons has reduced the incidence of side effects, characteristic of standard interferon treatment regimens.

Although SVR does not have a strong correlation with patient survival due to the need for long-term follow-up, the absence of detectable HCV RNA indicates a decrease in the severity of liver damage, decreased fibrosis and minimized risk

occurrence of recurrent disease. In addition, two large studies conducted in Japan showed that interferon treatment is associated with a reduced risk of developing HCC, which is important for those who achieve SVR.

Patients who fail to achieve SVR are given a second course of treatment. The decision on this is based on the following main points:

• the nature of the previous answer;
• the type of previous therapy and the potential for a new type of treatment;
• severity of liver damage;
• virus genotype and the presence of other prognostic factors;
• tolerance to previous therapy.

The possibility of achieving SVR in patients receiving re-treatment with pegninterferon in combination with ribavirin after monotherapy, or using a standard interferon/ribavirin treatment regimen, is currently being discussed. However, continuing repeated therapy without adjusting the treatment regimen may lead to a decrease in the effectiveness of therapy.

Patients who do not respond to peginterferon/ribavirin therapy at optimal doses pose a serious problem, especially in the presence of liver fibrosis or cirrhosis.

Patients with advanced fibrosis or cirrhosis are at increased risk of developing liver decompensation and should be considered candidates for re-treatment, especially if monotherapy is ineffective. Patients with moderate fibrosis and active liver disease should be given repeat therapy.

Approximately 30% of patients with HCV infection have normal ALT levels, and 40% have enzyme activity levels 2 times higher than the upper normal level. Despite mild histological changes, most of these patients tend to progress to liver fibrosis and cirrhosis.

Patients with normal ALT levels, minimal and weak otological activity of hepatitis without fibrosis can be subject to dynamic observation without antiviral treatment (control examination once every 6 months).

When carrying out etiopathogenetic treatment, it is necessary to remember the possibility of developing such side effects as pyrogenic

reaction and flu-like syndrome, depression, insomnia, asthenic syndrome, headache, skin itching and rash, alopecia, anorexia, as well as changes in clinical blood test - neutropenia, thrombocytopenia, anemia. Changes in biochemical parameters are also possible: increased activity of alkaline phosphatase, LDH, increased levels of creatinine and urea nitrogen in the blood serum.

The development of influenza-like syndrome can be prevented by taking paracetamol (no more than 3 g/day) or ibuprofen (in the absence of cirrhosis) simultaneously with the IFN injection.

Among the severe complications of interferon therapy, mental disorders are often observed. Often, during etiopathogenetic therapy, severe depression develops, requiring emotional support, psychotherapeutic assistance, and sometimes the prescription of antidepressants from the group of serotonin reuptake inhibitors.

To avoid the development of insomnia, ribavirin should be taken in the evening, but not at night. In severe cases, the use of tricyclic antidepressants is recommended.

Changes in lifestyle will help stop the formation of asthenic syndrome, physical activity, increasing the volume of fluid taken.

Skin itching and rashes observed with the above treatment can be treated with antihistamines and ointments based on glucocorticosteroids.

The alopecia that is sometimes observed is reversible; in these cases, it is useful to conduct psychotherapeutic conversations with patients.

With the development of anorexia, the diet is supplemented with enriched nutritional mixtures, and if necessary, prokinetics are prescribed.

Myalgia can be relieved by taking non-steroidal anti-inflammatory drugs (in the absence of contraindications to them).

• If the absolute number of neutrophils decreases to less than 750 cells/μl, it is necessary to consider reducing the dose of interferon by 2 times.
• In case of neutropenia with an absolute cell count of less than 500/μl, treatment should be interrupted until the absolute number of neutrophils increases to 1000/μl.

The development of thrombocytopenia requires appropriate medical tactics:

• If the platelet count decreases to less than 50,000 cells/μl, it is recommended to reduce the dose of IFN-a by 2 times.
• In cases where the absolute platelet count decreases to less than 25,000 cells/µl, treatment should be interrupted.

If anemia is detected (decreased hemoglobin level< 10 г/л, но у 8,5 г/дл) на фоне противовирусного лечения дозу рибавирина снижают до 600-800 мг/сут. У больных с заболеваниями сердечно-сосудистой системы доза препарата снижается аналогично уже при падении гемоглобина более 2 г/дл от исходного или при его уровне < 12 г/дл. Если появляются жалобы на похудание и утомляемость, необходимо исследовать функцию щитовидной железы (анализ крови на антитела к тиреоглобулину и антитиреопероксидазную активность сыворотки крови) каждые 2 месяца. У пациентов с нарушениями функции щитовидной железы в анамнезе контроль ТТГ должен проводиться один раз в месяц.

During treatment, autoimmune diseases may worsen: autoimmune hepatitis, idiopathic thrombocytopenia, hemolytic anemia, diabetes mellitus. Other autoimmune syndromes and diseases that arise or manifest during the administration of IFN-a include psoriasis, rheumatoid arthritis, SLE-like syndrome, sarcoidosis, and PBC. It is difficult to predict the occurrence of such complications. Before starting therapy, it is necessary, firstly, to carefully verify the diagnosis of hepatitis C and, secondly, to determine the initial spectrum of autoantibodies as completely as possible. The increased risk of developing autoimmune complications in patients with HLA haplotypes DR3, DR4, DR52 and DQ2, i.e., haplotypes associated with autoimmune hepatitis and other autoimmune diseases, should be taken into account. To monitor IFN therapy, a monthly clinical examination of the patient is recommended to determine the activity of transaminases (AlAT, AST) and other biochemical parameters, as well as a hemogram.

It should be noted that side effects such as anemia, weakness, depression are significantly more often observed with combination therapy.

HCV infection is common after liver transplantation, and the extent to which it progresses depends on the patient's immune status. The frequency of recurrent HCV infection correlates with the viral load at the time of surgery, the age of the donor, and the severity of immunosuppression in a particular individual in the postoperative period.

Biochemical remission at the end of treatment is assessed by the normalization of ALT. After completion of therapy, the criteria for complete remission are normalization of ALT levels and the disappearance of HCV RNAhi in the blood.

With IFN therapy, some patients may develop relapses of chronic hepatitis C during treatment, which, according to some authors, is due to the formation of antibodies to reaferon. In such cases, it is advisable to check for the presence of antibodies to IFN and, if they are detected, discontinue reaferon and continue treatment with natural leukocyte interferon.

Stable biochemical remission means the preservation of normal ALT activity 6 months or more after cessation of therapy. Stable complete remission in patients with chronic hepatitis C includes normal activity of AST, ALT, absence of HCV RNA 6 months or more after cessation of therapy.

If the patient does not respond to interferon therapy within 3 months of treatment, i.e., he continues to have hyperfermentemia and viremia, then IFN treatment should be discontinued. Virological control is carried out at the 12th week (3 months) of treatment.

If, after completing a 6- or 12-month course of IFN therapy, a relapse of the disease occurs, a second course of IFN treatment is possible, the response to which may be higher than the first. IFN-os is re-prescribed at a dose of 3 or 5 million IU per day intramuscularly 3 times a week for at least another 12 months. With this continuous repeated course of treatment, a response is achieved in 40-80% of patients.

However, if by the end of a 6-month course of IFN therapy only ALT activity normalized and viremia did not disappear, then with repeated IFN therapy only ALT normalizes, and HCV RNA rarely disappears in them.

Response to treatment is considered durable if a negative HCV RNA test and normal ALT levels are observed 6 months after completion of the full course of treatment.

Currently, to increase the effect of a repeated course of IFN therapy, a combination of IFN-a with ribavirin is used at a dose of 14 mg/kg per day.

Even in patients who did not respond to the first course of IFN therapy, a repeated course combined with ribavirin allows obtaining a positive response in 20-25% of cases. In individuals who responded to the first course of interferon therapy (at least transiently), repeated treatment combined with ribavirin increases the effect to 50-70%.

If stable complete remission is achieved 6 months after the end of treatment, it is recommended to continue monitoring the patient for at least 2 years with a frequency of 1 time in 6 months and subsequent liver biopsy.

As noted above, ribavirin (arviron, virazol, rebetol, ribavin, ribamidil), an analogue of guanosine, is widely used in the treatment of patients with chronic hepatitis C. The drug has a virusostatic effect against many DNA and RNA viruses, including those that are not sensitive to other antiviral drugs. The use of ribavirin for chronic hepatitis C does not reduce viremia, but has an immunomodulatory effect and, possibly, an immunosuppressive effect, normalizes ALT levels and improves the histological picture of the liver. Monotherapy with ribavirin for a year is relatively well tolerated by patients.

Only in 10-15% of cases the drug gave adverse reactions in the form of fatigue, dizziness, nausea, itching of the skin, and in a number of patients - hemolysis with a subsequent increase in serum iron content, as well as an increase in the concentration of iron in hepatocytes, which is known to contribute to the progression of fibrosis and deterioration in the effectiveness of IFN therapy. Ribavirin is taken orally at a dose of 1200 mg per day, divided into two doses (morning and evening).

Contraindications for the use of ribavirin are severe diseases of the cardiovascular system, thyroid gland, hemoglobinopathies, chronic renal failure, autoimmune hepatitis and decompensated liver cirrhosis, pregnancy, and age under 18 years. When using the drug, it is advisable before starting treatment, and then at the 2nd, 4th, 8th week of treatment and then regularly, as necessary, to conduct a clinical blood test (erythrocytes, leukocytes, leukocyte formula, platelets), a study of electrolytes, determination of creatinine levels, performing liver function tests. Women of childbearing age should use effective contraceptives for 6 months after treatment.

Some drug interactions have been described for ribavirin. Thus, when taken simultaneously with products containing magnesium and aluminum or simethicone, the bioavailability of the drug decreases,

Contraindications to antiviral therapy for chronic hepatitis with ribavirin are divided into absolute and relative.

Absolute contraindications:

• end-stage renal failure;
• anemia and hemoglobinopathies;
• pregnancy and lactation;
• non-compliance with contraception during treatment;
• uncompensated diseases of the cardiovascular system.

Relative contraindications:

• hypersensitivity to ribavirin;
• thyroid diseases;
• hemoglobinopathies (thalassemia, sickle cell anemia);
• epilepsy;
• decompensated cirrhosis of the liver;
• autoimmune hepatitis, other autoimmune diseases;
• age under 18 years;
• elderly age;
• uncontrolled arterial hypertension;
• hemoglobin level< 12 г/л у женщин и < 13 г/л у мужчин.

The optimal antiviral treatment regimen includes pegylated interferon-a2a at a dose of 180 mcg per week or pegylated interferon at a dose of 1.5 mcg/kg body weight per week + ribavirin in doses corresponding to body weight. The duration of treatment depends on the HCV genotype.

If a relapse occurs and in the absence of contraindications to ribavirin, it is recommended to start combination therapy with IFN + ribavirin for 6 months or a repeat course of monotherapy at a dose of 3 million IU for 12-18-24 months. In both cases, a permanent response can be obtained in 60% or more of patients. Combination therapy for recurrent chronic hepatitis C is 10 times more effective than IFN-a monotherapy.

It should be noted that ribavirin can cause side effects (fatigue, depression, dizziness, nausea, itching), and it is also possible to develop hemolysis with a subsequent increase in the concentration of iron in the blood serum and in liver cells. In turn, the accumulation of iron in hepatocytes increases fibrosis and reduces the effectiveness of therapy. To prevent the development of such an effect, it is advisable to carry out vomiting before carrying out combination therapy, primarily in those patients who, even before the combination therapy, had an increase in iron levels in the blood serum. We have proposed a treatment regimen for such patients with preliminary cytapheresis. In the treatment of chronic viral hepatitis, interferon inducers, in particular cycloferon, are also used. The drug is prescribed intramuscularly in a dose of 2 ml on days 1, 2, 4, 6, 8, 10 and 12 of the course of treatment, followed by switching to oral administration. A combination of cycloferon and interferon is advisable.

The use of ursodeoxycholic acid in the treatment of chronic hepatitis C is an adjuvant. In the presence of cholestasis syndrome, UDCA reduces the incidence of biochemical relapse of hepatitis.

Currently, studies are being conducted on the effectiveness of treating chronic hepatitis C with the following drugs in monotherapy, as well as in combination with pegylated interferons

• interleukin-2, -12,
• amantadine,
• mycophenolate mofetil,
• dihydrochloridagistamine,
• thymosin-a,
• VX-497.

The coincidence of the spectrum of pharmacodynamic activity of interleukin-2 (rIL-2) with the structure of immune dysfunctions in chronic hepatitis C justifies its use in treatment regimens for this disease. The domestic drug roncoleukin contains recombinant human IL-2 (rIL-2) as an active principle. The immunotherapeutic effect of rIL-2 is realized by replenishing the deficiency of endogenous interleukin-2, stimulating clonal proliferation of immunocompetent cells, prolonging the life of activated immunocompetent cells by reducing the level of apoptosis, restoring the Tm/Tn2 balance and correcting the cytokine regulation profile, increasing the functional activity of mononuclear phagocytes and production of endogenous interferons.

The use of roncoleukin in monotherapy is carried out according to two treatment regimens:

• Scheme I - intravenous administration of the drug 0.5 mg 2-3 times a week for 8 weeks; only 16-24 injections,
• Scheme II - intravenous administration of the drug 0.5 mg 3 times a week for the first two weeks and further subcutaneous administration of 0.5 mg 3 times a week for the remaining 6 weeks, a total of 24 administrations.

Currently, the largest amount of data on the feasibility and effectiveness of treating patients with chronic hepatitis C with roncoleukin, as well as its tolerability, has been obtained using a monotherapy regimen

A regimen of combination therapy with roncoleukin in combination with IFN-a drugs was first proposed and pathogenetically substantiated for the treatment of patients with chronic hepatitis C who have minimal biochemical histological activity of the process, including for patients who have not responded to interferon therapy. According to this scheme, roncoleukin is prescribed during treatment with IFN-a drugs intravenously at 0.5 mg 2 times a week for the first 8 weeks; 16 introductions in total.

During treatment with roncoleukin, the viral load decreases, including in monocytes, and the histological picture of the liver improves. The drug promotes the activation of the initially reduced cellular component of immunity and has a modulating effect on the humoral component. It should be noted that the drug was well tolerated and there were no serious side effects. A short-term increase in temperature to subfebrile values ​​during its administration was observed in 14% of patients.

The accumulated experience has made it possible to determine the principles of roncoleukin therapy:

• possibility of use in patients with contraindications to IFN therapy;
• possibility of use in patients with minimal histological and biochemical activity of the pathological process;
• the possibility of combining IFN and its inducers with drugs, overcoming the developing resistance to them.

According to Italian clinicians, in the majority of patients with chronic hepatitis C who have not previously responded to interferon-a monotherapy, combination three-component therapy - interferon-a + ribavirin + amantadine (midantan, symmetrel) - can be effective. Based on the results of their clinical study, it was concluded that the addition of amantadine hydrochloro-RVDA (200 mg per day orally) to interferon-osr therapy in combination with ribavirin more than doubled the number of patients in whom, after 12 months treatment, a clear response to therapy was achieved (up to 68%). Moreover, a year after the end of three-component therapy, a stable response occurred in 25% of patients, while among patients receiving two-component treatment, this figure did not exceed 4%.

A pharmacological substance with the working name VX-497 is at the stage of clinical trials, which is similar in its mechanism of action to ribavirin, but, according to the developers, is ten times more effective than it

Treatment of chronic hepatitis C patients with concomitant diseases requires special approach, development of special interferon therapy tactics. It is important to make sure that the use of interferon is appropriate for a particular patient (the presence of HCV replication, a persistent or wave-like increase in AST activity in combination with moderate or pronounced morphological activity in the liver). It is important to evaluate the leading pathology. The decisive factor may be the rate of progression of the concomitant disease. If it develops rapidly, treatment of chronic HCV infection with interferon in most cases should be abstained.

In this regard, one should also remember the likelihood of drug interactions between interferons and other medications taken by the patient, especially since they have not been fully studied. Use interferon-a with caution simultaneously with opioid analgesics, hypnotics and sedatives, and with drugs that potentially have a myelosuppressive effect. Interferons can influence oxidative metabolic processes. This should be taken into account when prescribed simultaneously with drugs that are metabolized by oxidation (including xanthine derivatives - aminophylline and theophylline). When using interferon simultaneously with theophylline, it is necessary to monitor the concentration of the latter in the blood serum, and, if necessary, adjust the dosage regimen. Combination with chemotherapeutic drugs (cyclophosphamide, doxorubicin, teniposide) increases the risk of developing toxic side effects and interferon therapy 1 severity and duration), which can seriously threaten the patient’s life.

For the treatment of chronic hepatitis C in patients with oncological diseases You can use standard doses of IFN if the following conditions are met: the presence of clinical, laboratory and morphological indicators of hepatitis C activity, remission of the underlying disease, absence of chemotherapy or radiation therapy.

Experimental studies have revealed the toxic effect of interferon therapy on the reproductive function of animals. The significance of this data for humans is unknown. However, CHCV is not treated with etiotropic drugs during pregnancy. Infection of a child is possible if the mother has active viral replication during pregnancy and childbirth, but even in this case, the vertical mechanism of transmission of the disease is realized only in 4-10% of cases.

It is unknown whether components of interferon-a preparations are secreted from breast milk. Due to the possible risk of adverse reactions in breastfed infants, if interferon therapy is necessary, the mother should stop breastfeeding. Women of childbearing potential should use reliable methods of contraception during treatment with interferon drugs.

Treatment of chronic hepatitis C in patients with autoimmune disorders currently insufficiently developed. Therapy with interferon drugs in these cases should be strictly individual. In case of pronounced clinical and laboratory manifestations of an autoimmune disease at the beginning of treatment, preference should be given to prednisone therapy.

Recent research results have demonstrated the effectiveness of treatment for people who inject drugs. This is very important, since injection drug addicts make up the majority of patients with hepatitis C. Their successful treatment will significantly reduce the spread of HCV infection.

Alcohol is an important cofactor in the progression of HCV infection to cirrhosis or HCC. A history of alcoholism is not a contraindication to treatment, however, drinking alcohol during a course of medication increases side effects. It is necessary to strongly advise patients to stop drinking alcohol or at least reduce its dose to 10 g or less per day. It is very important to start therapy alcohol addiction Before starting treatment for hepatitis, antiviral therapy in such individuals is considered only as part of a comprehensive treatment of the underlying disease.

Forecast

The most serious consequences of chronic HCV infection are liver fibrosis progressing to cirrhosis, end-stage liver disease, and HCC. The incidence of liver cirrhosis 20 years after acute infection is 17-55% in retrospective studies and 7-16% in prospective studies. However, no significant influence on the risk of liver disease progression has been established for such virological factors as viral load, genotype and the number of quasispecies. The risk of developing severe complications increases with infection in older people, males, the presence of immunodeficiency conditions, hepatitis B. An important role in the development of complications is played by regular consumption of more than 60 g per day of alcohol (6 glasses of beer, 4 glasses of wine or 3 cocktails) for men and 40 g per day for women. A negative impact on the course of the process can be caused by increased iron content, non-alcoholic liver steatosis, schistosomal co-infection, taking potentially hepatotoxic drugs, and the presence of environmental pollution.

14.11.2019

Experts agree that it is necessary to attract public attention to the problems of cardiovascular diseases. Some are rare, progressive and difficult to diagnose. These include, for example, transthyretin amyloid cardiomyopathy

14.10.2019

On October 12, 13 and 14, Russia is hosting a large-scale social event for free blood clotting testing - “INR Day”. The promotion is dedicated to World Day fight against thrombosis.

07.05.2019

The incidence of meningococcal infection in the Russian Federation in 2018 (compared to 2017) increased by 10% (1). One of the most common methods of prevention infectious diseases- vaccination. Modern conjugate vaccines are aimed at preventing the occurrence of meningococcal infection and meningococcal meningitis in children (even very young children), adolescents and adults.

Viruses not only float in the air, but can also land on handrails, seats and other surfaces, while remaining active. Therefore, when traveling or public places Ah, it is advisable not only to exclude communication with other people, but also to avoid...

Regaining good vision and saying goodbye to glasses and contact lenses forever is the dream of many people. Now it can be made a reality quickly and safely. The completely non-contact Femto-LASIK technique opens up new possibilities for laser vision correction.

Professor A.S. Khukhlina, head of the department of internal medicine, doctor, answered the questions medical sciences, professor, therapist and gastroenterologist of the highest category.

What is viral hepatitis? What types of viruses of this type can cause disease in humans?

Viral hepatitis is a group of infectious diseases with predominant inflammatory damage to the liver and intoxication syndrome. Most often, hepatitis can be caused by hepatitis viruses: A, B, C, D, G, E, TTV, Sen, etc. Also, the development of hepatitis is promoted by cytomegalovirus, Epstein-Barr virus, etc. The listed hepatitis viruses cause acute viral hepatitis, and the virus Epshein-Barr causes infectious mononucleosis, which also causes inflammation of the liver. Acute hepatitis B, B + D, C become chronic, can progress to cirrhosis of the liver and lead to the development of cancer of various localizations, thus significantly reducing a person’s life expectancy.

Is it true that the most dangerous of them is viral hepatitis C? What is it and what is the most threatening?

Viral hepatitis C (HCV) remains the main challenge to national health care: recently the number of patients with cirrhosis of the liver, liver cancer, pancreatic cancer, kidney cancer, uterine cancer - diseases caused by the hepatitis C virus has increased significantly. Mortality from hepatitis C in the next 5 years increased by 2.5 times. Ten-year survival of patients with liver cirrhosis is about 50%. The danger of the hepatitis C virus lies in the fact that it is characterized by a primarily chronic course without jaundice with minimal list clinical symptoms. This is why patients medical care are not addressed until irreversible complications develop, since in fact the disease is steadily progressing. Hepatitis C is most often diagnosed accidentally or with the appearance of symptoms at stages 2-4 of liver fibrosis, or already when hepatitis transitions to cirrhosis. These changes are irreversible, since liver failure progresses, disorders of brain function (encephalopathy), kidney function (hepatorenal syndrome) and blood coagulation disorders (bleeding) are added, from which the patient dies.

Where and how can you become infected with the hepatitis C virus, and is it true that even a drop of human blood, which is visible only under a microscope, is enough for infection?

Yes, indeed, for infection it is enough to cut yourself with a razor blade, on which the blood of a patient with viral hepatitis C remains, which was not sterilized for 30 minutes at a temperature of 60-1000 ° C after use by an infected person. And there are many such cases.

People who inject drugs and share needles and people who received blood transfusions before 1987 are at highest risk for hepatitis C virus infection. An intermediate (moderately increased) risk of HCV is observed in patients undergoing hemodialysis (artificial kidney machine), persons who have received organ transplants (transplantation) or who have received blood transfusions before 1992, and all those who, for health reasons, have received blood transfusions from donor, and then tested positive for HCV markers, persons with liver diseases of unknown origin, infants born to HCV-infected mothers. The next category (high risk) includes medical workers who come into contact with the blood of a patient infected with the HS virus, persons who have sexual contact with many partners or with one infected partner, persons who often perform manicures, pedicures, piercings, tattoos, shaving with possible damage to the skin that is serviced in salons where the staff does not follow the rules of asepsis and antiseptics, and reusable instruments are not properly sterilized. People at all risk groups for hepatitis C should be tested for HCV markers and vaccinated against hepatitis B, as they are also at risk of contracting this infection.

Why is the number of patients with hepatitis C increasing at a very rapid pace? Apart from the lack of a vaccine, what else is causing this? Can we talk about a hepatitis C epidemic?

The main reason for the continuous spread of viral hepatitis is insufficient sanitary and epidemiological supervision of compliance by private establishments (hair salons, dental offices, etc.) with the rules of asepsis, antiseptics, sterilization of reusable instruments, since it is a frequent source of infection for a significant part of the population, as well as insufficient awareness of the population about this problem, belonging to risk groups with an increased likelihood of infection.

Now public organizations and the media, demonstrating unofficial statistics on the infection rate of the population and the incidence of viral hepatitis, unanimously speak about the “unrecognized” epidemic of viral hepatitis C, but there is no official information about this fact.

Hepatitis C incidence rates

According to experts, up to 10% of the population is infected with the hepatitis C virus, a fifth of whom are patients with chronic viral hepatitis C. The incidence is indeed constantly growing, but no one has accurate statistics on the prevalence of this disease, since the disease has an asymptomatic course. Currently, about 500 people are registered in the register of patients with viral hepatitis C awaiting treatment using funds allocated under a quota for the Chernivtsi region as part of the National Program to Combat Viral Hepatitis, as well as funds from the Regional Program of the Department of Health. The regional sanitary and epidemiological station maintains a register of all patients who are examined in public and private laboratories, medical institutions cities and regions, and this data is, of course, more accurate.

Who gets hepatitis? Are these socially vulnerable segments of the population or quite prosperous people?

Different faces get sick social groups. First of all, these are injection drug users, HIV-infected and AIDS patients often have co-infection with the hepatitis C or B virus, persons who have received blood transfusions that are not quarantined for the hepatitis C virus or have undergone surgery for health reasons with non-sterile instruments (in the ATO zone), patients chronic disease stage 5 kidneys, constantly perform hemodialysis procedures, persons leading an immoral lifestyle with frequent changes of sexual partners, or with unknown persons in places of recreation, or a regular partner sick with chronic viral hepatitis C, as well as all those persons indicated in the groups the risk of accidental HCV infection in beauty salons and private dental offices in conditions of careless use of non-sterile instruments by specialists.

How to prevent hepatitis C infection? Is there a prospect that a vaccine against this infectious disease will be invented in the near future?

You can prevent HCV infection if you turn on the instinct of self-preservation and follow basic safety rules when servicing in salons, for example, use your own sterile equipment, choose salons with employees you trust. The basic rule of prevention is not to belong to, or to leave, if possible, a risk group for increased likelihood of HCV infection, if possible. It is known that a vaccine against the hepatitis C virus has already been created and is at the stage of clinical testing. I would like to believe that it will soon be introduced into healthcare practice.

Hepatitis C is said to be a “soft” killer. Is the course of the disease really almost asymptomatic? What early symptoms of the disease suggest hepatitis C?

The latent (incubation) period for acute HCV is about 50 days (from 20 to 140). Symptoms of acute hepatitis C may never appear, or may be disguised as influenza, ARVI, food poisoning. Manifestations of infection can generally be detected only when hepatitis turns into cirrhosis. HCV is a disease with a predominantly asymptomatic course, diagnosed more often by chance, when people are examined for other diseases: pancreas, gallbladder, thyroid gland, blood vessels, heart, kidneys, blood (anemia), joint diseases, and during the examination HCV is detected .

More often than other symptoms, asthenia, general weakness, fatigue, a feeling of heaviness or pain in the right hypochondrium, bloating, loss of appetite, and skin rash occur. A small number of people experience nausea and stool disorders.

Chronic hepatitis C is characterized by an increase in the size of the liver and spleen (ultrasound), periodic fluctuations in biochemical indicators of the functional state of the liver. During the active phase of hepatitis, the activity of aminotransferases (markers of liver damage) increases. Markers of the presence of the hepatitis virus in the body are the presence of diagnostic titers of antibodies to the RNA of the hepatitis C virus, the presence of RNA of the virus in the blood, which can be confirmed by polymerase chain reaction in any laboratory in the city.

In your practice, do patients with hepatitis seek medical help in a timely manner or not at all?

Patients arrive late. Unfortunately, the majority of the population does not want to comply with the principles of medical examination of the population, which were started in the last century. I mean an annual general examination: chest x-ray, ECG, clinical blood test, biochemical blood test, which indicates functional state liver, kidneys, glucose levels, blood lipid spectrum, etc., ultrasonography internal organs and the like. And, of course, it would be easier for us to diagnose the disease on early stage, take measures to quickly eradicate the virus.

Is it possible to cure hepatitis C?

Despite the fact that at one time there was a large number of refusals to vaccinate against hepatitis B, and now there is a shortage of vaccines, is there a risk of an increase in the number of patients with hepatitis B in the near future?

Of course, the number of patients with hepatitis B is also increasing, since the risk factors and risk groups for infection for both hepatitis are the same, parenteral, sexual, vertical (from mother to fetus) mechanisms of infection are also the same. If the population's awareness of the importance of vaccination does not increase and the instinct of self-preservation does not work (to protect itself from risk factors), and the conscience of those service workers whose careless attitude contributes to the increase in the prevalence of viral hepatitis does not appear, the situation will worsen significantly.

How to kill the hepatitis C virus is a pressing issue due to the spread of infection and its ability to lead to serious complications. There are dozens of traditional and non-traditional therapies. There are experimental and classical schemes to combat the disease. Cases of self-healing from hepatitis C have been recorded. Doctors recommend a treatment regimen. But the last “word” always belongs to the patient. What to trust and how to treat?

When hepatitis C is diagnosed, antiviral treatment does not always need to be started immediately. In approximately 5-20% of patients, the body is able to kill the viral hepatitis infection on its own. How? The immune system is triggered. If it is strong, the patient is young and does not suffer from anything other than hepatitis, the doctor may postpone the therapeutic course. At the same time, attention is paid not only to the age of the infected person, but also:

• genotype of the identified virus;
• duration of infection;
• virological load;
• the patient's tendency to develop cirrhosis.

When choosing a means of treating a disease, doctors pay Special attention precisely on the last factor. To determine how likely a patient is to have cirrhosis, the doctor conducts a study to identify specific immunogenetic markers.

Questioning the patient is also important. The tendency to develop liver cirrhosis is genetically determined.

If the risk of developing a complication is high, treatment begins immediately, even with other prerequisites for self-recovery. Cirrhosis is an irreversible process. The replacement of most normal hepatocytes with nonfunctional fibrous tissue is the reason for organ transplantation. And this threatens the patient's life. Firstly, the liver may not take root. Secondly, selecting a donor organ is difficult.

The main goal of therapy is eradication of the virus, that is, its removal from the body. If this is not possible, the course of treatment is aimed at slowing the progression of inflammation in the liver. This prevents the infection from progressing to cancer or cirrhosis.

The effectiveness of therapy depends on the following factors:

1. The patient's age and initial health.
2. Liver conditions at the time of hepatitis diagnosis.
3. Viral load, that is, the amount of detected pathogen in the blood.
4. Forms of hepatitis. It can be acute or chronic.

Drug treatment is based on the use of antiviral drugs. Direct-acting drugs are prescribed that attack the protein compounds of the hepatitis causative agent. The pathogen cannot reproduce further.

Until recently, the combination of Ribavirin and Interferon was considered the gold standard for hepatitis C therapy. However, this treatment was not safe. In addition, the effectiveness of therapy did not exceed 50%. Now there are more effective and safe drugs, capable of completely eliminating the virus. Among them are Ledipasvir, Sofosbuvir, Daclinase.

Antiviral therapy has contraindications. Among them:

• intolerance to individual components of the drug;
• unsuccessful treatment with similar drugs in the past.

In addition, new generation products are expensive. Every month you have to spend from 500 to 2500 dollars. Therefore, new products are available to a limited number of patients. Doctors are forced to prescribe the old treatment regimen.

Auxiliaries are mandatory when treating with both new generation drugs and Interferon. The main ones are hepatoprotectors. They protect liver cells and support their performance. Doctors often prescribe Essentiale and Silimar.

The choice of therapy is always individual and based on the results of the examination. Duration of use of medications is at least 3 months. In some cases, the patient has to take medications for years.

Research results have shown that the hepatitis C virus is highly resistant. It can remain active in dried blood for approximately 6 weeks. The lifespan of a virus in the air directly depends on temperature:

1. If the atmosphere is heated within +2-22 degrees, the pathogen can remain active for up to 7 days.
2. When the air temperature changes in one direction, the activity of the virus decreases.

It turns out that if the task is to kill a pathogen in the external environment, it is necessary to create conditions unfavorable for it. Cold will not destroy the pathogen, it will only reduce its activity. But boiling kills the virus.

If the hepatitis C virus is exposed to ultraviolet light, the pathogen dies instantly.

After the virus enters the body, a person may feel well for a long time, without even suspecting that he is infected. In this case, the causative agent of hepatitis can be released into the external environment along with saliva, blood and other biological fluids.

The following may be dangerous:

• blood dried on the surface of instruments (cosmetic and medical), razors and other objects;
• contaminated blood, semen and saliva that have come into contact with damaged skin or mucous membranes of a healthy person.

Outside the human body, at room temperature, the virus that causes hepatitis C can remain active for at least 16 hours. In some cases, the pathogen remains viable for up to 4 days.

It is worth remembering that you cannot become infected through airborne droplets or contact (shaking hands, hugging).

The infection can persist for a long time donated blood. The pathogen survives in a reservoir for about 10 months.

The virus that causes hepatitis C is not resistant to various disinfectants. However, simply washing your hands after visiting public places may not be enough.

To quickly eliminate the viral agent, it is necessary to disinfect the damaged skin surface with any antiseptic. The pathogen can be destroyed by:

• boric, hydrochloric or phosphoric acid;
• hydrogen peroxide;
• Miramistin or Chlorhexidine.

During surgical operations, an iodine solution is used to treat the intervention area. This helps prevent the virus from entering an open wound.

What to do with surgical instruments? They are always sterilized in special devices where they act on equipment high temperatures or ultraviolet rays.

In beauty salons, alcohol-containing liquids can be used for disinfection. For example, ethyl alcohol is a powerful antiseptic. In it, the virus dies within the second minute. Ethyl helps destroy the protein structure of the hepatitis C pathogen.

When treating a potentially contaminated item with alcohol, do not allow it to evaporate for several minutes. Otherwise, disinfection is not effective.

You can get rid of infection on things by boiling them. If the water temperature is above 50 degrees, the pathogen will die in half an hour. When the temperature reaches 100 degrees, the virus is destroyed in the second minute.

Therefore, simply washing items with dried blood at 40-60 degrees may not be enough.

If infected blood comes into contact with your skin, you should:

1. Use bleach. To do this, the powder is dissolved in water in a ratio of 1 to 100. The solution is effective against hepatitis and tuberculosis viruses.
2. If the skin is damaged by a sharp object, it is necessary to compress the wound, trying to squeeze out the blood from it. After this, the cut site must be treated with soapy water and lubricated with ethyl alcohol or iodine.
3. If infected blood gets into the eyes, they should be rinsed well with a 1% boric acid solution.
4. If there is a possibility of the virus getting into the mouth, it is necessary to spit out as much saliva as possible and rinse the cavity with a 70% alcohol solution or manganese solution.
5. If the virus gets into the nasal passages, you need to drip a silver solution. In pharmacies it is called Protargol.

In most cases, after performing the steps described above, the hepatitis C virus dies. To verify this, you need to undergo a comprehensive examination. It is carried out at 1, 4 and 12 weeks after the suspected infection.

Because the effective treatment hepatitis C requires significant financial costs, non-traditional therapy regimens are becoming widely popular. One of them is the method of Professor Neumyvakin, based on the use of hydrogen peroxide.

The drug should be used as follows:

• on the first day, take 2-3 drops of peroxide dissolved in a tablespoon of water three times a day;
• daily the amount of peroxide is increased by 1 drop;
• when the dosage reaches 10 drops, stop increasing the dose and take the medicine for another 10 days.

Another question is the effect of the drug on the body.

Neumyvakin emphasizes that serious ailments are possible:

• vomit;
• diarrhea;
• dizziness;
• weakness.

Therefore, before starting therapy using the Neumyvakin method, it is important to consult with your doctor. A history of organ transplantation may be a contraindication to the use of the experimental regimen.

Traditional methods of fighting the virus

If a patient has contraindications to drug treatment for hepatitis C, you can use the practices of herbalists. They advise using medicinal herbs that have anti-inflammatory, immunostimulating, analgesic and antispasmodic effects.

Herbal therapy is aimed at the body's synthesis of interferon. Human cells are capable of producing it themselves. Interferon has an inhibitory effect on the virus and prevents the development of complications of hepatitis.

For this use:

• a decoction made from milk thistle seeds;
• alcohol tincture of milk thistle seeds;
• powder made from dried dandelion root;
• a decoction made from unpeeled oats;
• product based on Caucasian hellebore;
• infusion made from corn silk;
• black radish juice mixed with natural honey;
• water tincture of perennial daisy;
• tincture of lovage (seeds and leaves).

In addition, natural juices of lemon, blueberries, carrots and cabbage can be used. Your doctor will tell you how much to take and according to what schedule.

Doctors have proven that the human body is able to get rid of the virus that causes hepatitis C on its own. This is possible if a person has a strong immune defense. The state of immunity plays a role important role and in standard treatment of the disease. To reduce therapy time and also avoid dangerous consequences hepatitis, you should follow a certain diet, refusing bad habits.

Additionally required:

1. Observe drinking regime, drinking at least 7-8 glasses of clean still water per day.
2. Avoid eating fatty, fried and spicy foods, chocolate, baked goods and smoked meats.
3. Avoid alcohol.
4. Provide yourself with a nutritious diet high content plant food.
5. Avoid prolonged fasting.
6. Eat small meals. It is advisable to have meals 5-6 times per day, preparing 200-gram portions.
7. Limit your sugar intake.

Which virus genotype is more difficult to kill?

In total, doctors were able to identify 11 different genotypes of this virus, but only six are recognized by the World Health Organization:

• the first is divided into 3 subtypes: a, b, c;
• the second a, b, c and d quasitypes;
• the third genotype is divided into a, b, c, d, e, f subtypes;
• the fourth strain also has quasitype g;
• The fifth and sixth genotypes of hepatitis C have only one a-strain.

The most common is genotype 1. It infects about 46% of all patients with hepatitis C. Less commonly, in about 30% of cases, a 3rd strain of the pathogen is diagnosed.

The traditional treatment regimen based on the use of Interferon is the most responsive to genotype 1b. Since interferon-free treatment regimens have been developed, it is possible to get rid of this type of infection.

Treatment for hepatitis C is long and expensive. Therefore, doctors recommend taking preventive measures to prevent infection. If this fails, treatment should be prescribed by a doctor. If drug therapy is not possible for some reason, the doctor may recommend unconventional methods.

Chronic viral hepatitis C(CHC) is an inflammatory liver disease caused by the hepatitis C virus (HCV) that lasts 6 months or more and can lead to or be associated with cirrhosis. It is believed that for the purposes of clinical practice it is necessary to distinguish between the following HCV genotypes: 1a, 1b, 2a, 2b and 3a. On the territory of Russia, genotypes 1b and 3a predominate. The disease is characterized by a successive change of acute, latent and reactivation phases, liver cirrhosis and hepatocellular carcinoma. In the acute phase, complete elimination of the virus and recovery are possible in 10-15%. The latent phase is more often registered in women as “chronic virus carriage.” The presence of HCV RNA in the blood does not necessarily indicate viral replication, since pathological changes in the liver tissue may be absent or minimal. The presence of the virus in the blood in the absence of histological changes in the biopsy specimen suggests infection with non-virulent strains of the virus, the body's tolerance to HCV, as well as possible extrahepatic replication of the virus.

According to the 2000 American Consensus Hepatitis C criteria, optimal approaches for diagnosing and monitoring the disease have now been developed. Tests that detect antibodies to the virus include the ELISA method, which includes kits containing HCV antigens from the core and non-structural genes, and recombinant immunoblotting methods (RIBA). Targeted amplification tests, including polymerase chain reaction (PCR) or transcription-mediated amplification (TOA), are designed to detect HCV RNA. A biopsy can provide histological characterization of liver damage, but does not diagnose HCV infection. In patients with positive ELISA results, the presence of persistent HCV infection must be confirmed by qualitative determination of HCV RNA. Testing HCV RNA levels (or viral load) using methods such as quantitative PCR (qPCR) or branched DNA amplification test provides accurate information. Quantitative detection of the virus provides important information about the effectiveness of treatment.

To confirm the diagnosis in a laboratory, it is necessary to examine the blood using ELISA for the presence of antibodies to HCV and ALT activity. Antibodies to HCV can be found not only in the blood, but also be part of the CEC. The severity of inflammatory activity, the stage of fibrosis, or the presence of already formed cirrhosis can predict the response to interferon therapy. All patients with CHC are potential candidates for antiviral therapy (AVT). The indication for etiopathogenetic therapy is moderate or severe necrotizing inflammation and/or fibrosis of the liver with detectable levels of HCV RNA in the blood serum. The goal of therapy for chronic hepatitis C is eradication of the virus, slowing the progression of the disease, improving the histological picture of the liver, reducing the risk of developing HCC and improving health-related quality of life.