Hepatitis C - symptoms and treatment, the first signs. Side effects of antiviral therapy

A retrospective study of chronic hepatitis C (CHC) suggests that, on average, 20% of patients develop cirrhosis of the liver (LC) within 20-30 years. The rate of formation of cirrhosis depends on a number of factors. A slow increase in fibrosis in chronic hepatitis C is observed in young women in the absence of factors such as hepatic steatosis, iron overload syndrome, and alcohol abuse. A number of reasons determine the rapid formation of cirrhosis: advanced age at infection, male sex, systematic alcohol consumption of more than 50 g/day, the presence of co-infection with hepatitis B and/or HIV viruses, overweight (> 28 kg/m²), heterogeneity in the hemochromatosis gene, polymorphism of genes for a number of cytokines that play a key role in fibrogenesis. The average time to develop cirrhosis in persons infected after the age of 40 and who abuse alcohol is 13 years, and in young women in the absence of alcohol intake, cirrhosis develops after 42 years. In 32% of patients with chronic hepatitis C, the course is stable and is not accompanied by disease progression.

An important factor in fibrogenesis is the persisting activity of CHC according to laboratory data and morphological features. In patients with persistently normal levels of serum transaminases, the risk of developing CP C is 5%, while the presence of a 3-5-fold increase in serum ALT is associated with the rapid formation of CP C in 50% of patients. It has also been shown that the risk factors for the progression of fibrosis are: the presence of fibrosis in the liver tissue at the first biopsy, liver steatosis and the age of patients. The rate of progression of fibrosis is determined by prior fibrosis, steatosis, and lobular hepatitis. With chronic hepatitis C with a low degree of activity (IHA according to Knodell 4-8 points), 7-10% of patients are at risk of developing cirrhosis C, with chronic hepatitis C with a high degree of activity (IHA - more than 13 points), cirrhosis can develop in 71% of patients after 7 years . A prospective study of 404 patients with compensated LC C showed that over 85.7±36 months of follow-up, 28% of patients develop at least one complication of LC C, including hepatocellular carcinoma (HCC) in 19%, ascites in 17%, bleeding from varicose veins of the esophagus (EVV) - in 5%, decompensation of CP C (Child V/C) - in 17%, encephalopathy - in 2%.

The high incidence of LC C in chronic HCV infection and the risk of serious complications in this group of patients determine the objectives of antiviral therapy (AVT). The main goal of treatment is the eradication of the hepatitis C virus and the achievement of a stable remission of chronic hepatitis C, however, the possibility of achieving a sustainable virological response (SVR) in patients with cirrhosis C is significantly lower than in patients with chronic hepatitis C. Recent studies have shown that AVT helps to reduce the severity of fibrosis, therefore, in in patients with cirrhosis C without a virological response, the goal of antiviral treatment is to slow down the progression of the disease, reduce the risk of cirrhosis decompensation and the development of its complications, including HCC, B-cell lymphoma, cryoglobulinemia, extrahepatic manifestations, portal hypertension and hepatocellular insufficiency.

Of interest are the studies of M. Curry et al. (2005), who studied the effect of long-term therapy with low doses of peginterferon α-2b on the dynamics of portal hypertension in patients with chronic hepatitis C with fibrosis stage F3 and cirrhosis C (F4). The COPILOT study included 267 patients treated with colchicine 0.6 mg twice daily and 270 patients treated with pegintron 0.5 µg/kg once weekly for 4 years. Both groups were represented by patients who did not respond to combination therapy with interferon and ribavirin. 83% of patients in each group had cirrhosis C, 40% of them had signs of portal hypertension detected at endoscopy (vvvv or portal gastropathy). EGDS was performed at intervals of 2 years. The preliminary results of the study have been published.

In 5 patients with cirrhosis C, who did not receive β-blockers to correct portal hypertension, portal pressure was measured before treatment with pegintron. After 2 years of treatment with repeated EGDS, new EVV appeared in 11 of 66 patients treated with colchicine, and persisted in 5 of 66 patients treated with pegintron monotherapy. In all 5 patients, the initial portal pressure was 15 mm Hg. Art., after 24 weeks of treatment averaged 6 mm Hg. Art. Bleeding from EVV after 2 years was noted in 11 (9%) patients treated with colchicine and in one (1%) patient treated with pegintron. Ascites and hepatocellular insufficiency were also more frequently detected during treatment with colchicine (20 patients) than with pegintron (13 patients). Thus, long-term treatment with low doses of pegintron in patients with LC C can slow down the formation of EVV, reduce portal pressure, prevent bleeding from EVV and other complications of portal hypertension in patients with LC C who did not achieve SVR on previous combination therapy with interferon and ribavirin.

In recent years, AVT has undergone significant changes: since 2000, combination therapy with pegylated interferons α-2a and 2b and ribavirin has taken a leading position in the treatment of chronic hepatitis C and compensated cirrhosis C. The prognostic factors of response to treatment have been studied, it has become possible to correct a number of side effects of AVT, which made it possible to achieve SVR in 56-63% of patients with chronic hepatitis C who were included in the treatment. Patient adherence to treatment, adequate doses of drugs and the duration of AVT can increase SVR up to 72-75%. The greatest effect of combination therapy of chronic hepatitis C is observed in patients with HCV genotypes 2 or 3: a short course of treatment (24 weeks) with high adherence to treatment with pegylated IFN-α and ribavirin makes it possible to achieve success in 84-94% of cases.

The mandatory prescription of a combined AVT (IFN-α and ribavirin) to primary patients, the choice of optimal doses of drugs and the duration of treatment depending on the HCV genotype and viral load contribute to the increase in the effectiveness of AVT. In addition, it is necessary to correct the factors of adverse response to treatment (steatosis, cholestasis, iron overload syndrome) and side effects of AVT (depression, hemolytic anemia with ribavirin, leukocytopenia and thrombocytopenia with IFN-α treatment, thyroid dysfunction). Suboptimal doses of drugs used during AVT and insufficient duration of treatment contribute to the formation of a group of patients with chronic hepatitis C resistant to antiviral therapy, which makes it necessary to repeat AVT courses. Thus, it was shown that with a 48-week combined AVT, SVR was achieved in 72% of patients with HCV genotype 1b and low viral load. Subsequent exacerbation of chronic hepatitis C was observed in 3% of patients. At the same time, with 24-week AVT, SVR was observed only in 51% of patients of this category, and exacerbation of chronic hepatitis C and resumption of viremia 6-18 months after the end of AVT were observed in 40% of patients.

Despite the achievements of recent years, there remain categories of difficult-to-treat patients with chronic hepatitis C, which include patients with HCV genotype 1 and a high viral load and patients with cirrhosis C.

HCV genotype 1 and high viral load were found to be independent predictors of poor response to treatment. The reasons for this are not completely clear. The significance of mutations in the E2 and NS5A genes of HCV is being studied (the non-structural region of NS5A determines sensitivity to interferon). Elimination of hepatocytes infected with HCV genotype 1 during AVT is slower than with other genotypes. In the first 1-2 weeks of therapy, the viral load decreases by 1.6 log copies / ml in HCV genotype 1 and by 2.9 log copies / ml in genotype 2. The rate of death of infected hepatocytes is 0.1 per day in patients with genotype 1 and 0.26 per day for genotype 2, which is explained by differences in the immune response in patients and provides a basis for discussing the need for a more aggressive and possibly longer AVT in HCV genotype 1.

The treatment strategy for patients with cirrhosis and chronic hepatitis C who are infected with HCV genotype 1 and have a high viral load is closely related. SVR in the treatment of IFN α in the standard regimen of patients with chronic hepatitis C with HCV genotype 1 does not exceed 10%, regardless of the duration of treatment - 24 or 48 weeks. When using combination therapy (IFN α / ribavirin) for 48 weeks, SVR in such patients increases to 28-36%, remaining significantly lower than SVR in HCV genotypes 2 and 3 (64-79%). Treatment of chronic hepatitis C with HCV genotype 1 for 48 weeks gives better results (46-52%) than 24 weeks (29-42%). Thus, the HCV genotype determines the AVT strategy for CG C and LC C.

The level of viral load, as well as the genotype of the virus, does not affect the variant and severity of CG C. High viral load (more than 2x10 6 copies / ml or more than 800,000 IU / ml) can be detected in chronic hepatitis of low, moderate, high activity , with minimal changes in the liver or with LC C. However, the level of viremia clearly affects the frequency of achieving SVR: pegylated IFN α-2b 1.5 μg/kg once a week in combination with ribavirin at a dose of 800 mg/day with a high viral load provides SVR in 42% of cases, and at low - in 78%.

In recent years, a method has been developed for assessing the success of therapy based on the study of viral kinetics at an early stage of AVT. Early virologic response predicts SVR. The high adherence of patients with chronic hepatitis C to treatment and the evaluation of AVT prognosis based on early virological response data at the 4th or 12th week made it possible to increase the effectiveness of therapy in the group of all treated patients with chronic hepatitis C up to 90%. Refusal of standard IFN-α treatment regimens (3 million IU 3 times a week) with the transition to a combined AVT also contributes to an increase in the number of patients with an early virological response.

The study of early virological response based on the quantitative analysis of HCV-RNA using highly sensitive PCR allows you to identify patients who do not respond to AVT. If, after a 12-week AVT with pegylated IFN-α and ribavirin, the level of HCV-RNA decreased by two or more decimal logarithms, but the virus RNA is still detected in the blood, then it is advisable to continue the AVT for another 12 weeks, and then re-examine HCV- RNA. With his negative result, SVR ranges from 42 to 78%, depending on the viral load. A 72-week course of AVT seems appropriate, i.e., prolongation of treatment up to 1.5 years, which can significantly improve treatment outcomes. With persistent viremia with a drop in its level at week 12 by less than two decimal logarithms, the SVR ranges from 0 to 5%, which makes it possible already at the early stages to either abandon unpromising therapy for HCV genotype 1, or modify it, or switch to maintenance therapy with pegylated IFN α-2a (90 μg) or IFN α-2b (0.5 μg/kg) to slow the progression of cirrhosis C and prevent the development of HCC and lymphoma.

Thus, genotype 1b and a high viral load determine the category of “difficult” for the treatment of patients with chronic hepatitis C. In relation to this group of patients, it is necessary to strictly follow the rule of using the maximum effective doses of pegylated IFN α-2b (1.5 μg/kg) or IFN α- 2a (180 mcg) in combination with ribavirin at a dose higher than 13 mg/kg for a duration of treatment of 48-52 weeks. It is known that pegylated IFN α-2a and 2b differ from each other in pharmacokinetics and pharmacodynamics. An independent comparative assessment of the kinetics of the virological response to pegylated IFN α-2a at a dose of 180 μg/week and IFN α-2b at a dose of 1.5 μg/kg/week was carried out when combined with ribavirin at a dose of 15 mg/kg/day in primary patients with chronic hepatitis C. At the end of the course of treatment, the virological response to combination therapy with pegIFN α-2a/ribavirin and pegIFN α-2b/ribavirin in patients with HCV genotype 1 was 55% and 76%, respectively, which allows us to recommend the use of pegIFN α-2b as part of combined AVT in this category of patients. Currently, a number of authors propose to evaluate the early virological response at week 4 and, in the absence of a virological response, modify the treatment. Induction therapy with pegylated IFN α-2b at a dose of 3 μg/kg/week for 4 weeks or 2 μg/kg/week for 8 weeks is used, followed by the use of the drug at a dose of 1.5-1.0 μg/kg/week.

The triple regimen of combined AVT with the inclusion of amantadine 200 mg in addition to pegylated IFN-α and ribavirin has no advantages over the conventional regimen in the treatment of genotype 1b chronic hepatitis C with a high viral load.

In 2004, preliminary results of treatment of patients with HCV genotype 1 and a high viral load who did not respond to the first course of AVT with IFN α and ribavirin, a combination of α-thymosin-1 (1.6 mg 2 times a week subcutaneously), pegylated IFN α -2a (180 mcg per week) and ribavirin (1000-1200 mg/day) for 24 weeks. An early virological response at the 12th week of treatment was achieved in 47.8% of patients, the virological response after 24 weeks of therapy was maintained in 39.1% of patients with chronic hepatitis C, representing a "difficult" group for treatment. The additional drug (α-thymosin-1) did not add any new side effects and was well tolerated by the patients.

New strategies in the treatment of "difficult" patients with HCV genotype 1 and high viral load include extending the combined AVT to 72 weeks in patients who do not achieve an early virological response at week 4, which allows to increase SVR from 22% (at 48 weeks therapy) up to 51% and reduce the frequency of exacerbations.

The rationale for the treatment of chronic hepatitis C with an advanced stage of fibrosis or formed LC C was the data on a reduced risk of cirrhosis decompensation and the development of HCC, as well as regression of fibrosis in 60% of patients receiving AVT. The presence of portal fibrosis or cirrhosis C is considered an independent factor in the low SVR rate in HCV-infected patients. Patients with cirrhosis C generally respond poorly to standard IFN-alpha monotherapy, with an SVR of 5 to 20%. The effectiveness of combination therapy with IFN-α and ribavirin was 5-29% in this group. The use of pegylated IFN-α as part of a combination therapy for compensated cirrhosis C or chronic hepatitis C with bridging fibrosis made it possible to increase SVR to 44-50%.

It should be noted that even with monotherapy with pegylated IFN-α, histological improvement can be achieved in 54% of patients with compensated cirrhosis C. In a comparative study of the efficacy of pegylated IFN α-2a and 2b in patients with cirrhosis C, the presence of bridging fibrosis was a negative prognostic factor for achieving an early virological response. At the end of the 24-week AVT, the virological response in the 1st group of patients with cirrhosis C was 83%, in the 2nd — 60%. Thus, pegylated IFN α-2a may be the drug of choice in combination therapy for cirrhosis C. Even in the absence of a virological response to the combined AVT in cirrhosis C, there is an improvement in the histological picture in the liver (decrease in IHA and GIS).

The most significant improvement in morphological data occurs when SVR is achieved, which is accompanied by an improvement in the quality of life of patients with cirrhosis C, despite the presence of an advanced stage of the disease. Of interest are the data of Poynard et al. (2000), who observed 3010 patients with chronic hepatitis C with repeated liver biopsy (before AVT and 6-12 months after its completion) using various treatment regimens: monotherapy with IFN α-2b, combined AVT with IFN α or pegylated IFN α-2b and ribavirin for 48 weeks. In more than a third of patients who achieved SVR, the histological picture (GIS and IHA) in the liver improved, morphological dynamics was also noted in a third of patients without a virological response. Analysis of liver biopsies in patients with chronic hepatitis C who participated in four multicenter studies showed that in 75 (49%) of 153 patients, cirrhosis C after the end of therapy with GIS (fibrosis level) decreased by 1-3 points, which suggests the possibility of regression of fibrosis with CP C under the influence of persistent purposeful AVT.

In recent years, attempts have been made for antiviral treatment of decompensated cirrhosis C (Child B and C). It is known that 40% of all orthotopic liver transplantations are performed in connection with LC C. Patients with persistent viremia have a high risk of graft rejection reactions and infection of the donor liver with hepatitis C virus with rapid development (within 5-7 years) of LC C and/or HCC in the transplanted liver. In 2003-2004 the first publications on the use of AVT with low doses of interferon and ribavirin in decompensated cirrhosis C in candidates for liver transplantation appeared. It is proposed to start treatment with IFN-α 3 million IU daily and ribavirin 800 mg/day 4 months before the proposed operation. The regimen of daily administration of interferon can reduce the frequency of influenza-like syndrome, treatment for 4 months allows to achieve the maximum reduction in viremia (before surgery). In 9 (30%) of 30 patients with decompensated cirrhosis C (Child B or C) achieved a virological response at week 12, in 6 of them (20%) aviremia persisted after liver transplantation. Similar data on the possibility of developing SVR in 18-20% of cases of decompensated cirrhosis C have been published by a number of authors, the duration of observation of such patients lasts more than 3.9 years.

It is known that alcohol consumption significantly increases mortality in viral cirrhosis: the five-year survival rate of patients reaches only 43%, differing significantly in the Child A (66%), Child B (50%) and Child C (25%) cirrhosis groups. With continued alcohol intake, the risk of death in patients with cirrhosis C increases in the presence of factors such as advanced age, hepatocellular dysfunction (Child B or C), gastrointestinal bleeding, coinfection (HBV, HCV), smoking, and the absence of signs of acute alcohol abuse. hepatitis on liver biopsy. Among the mechanisms of the influence of alcohol on the progression of HCV infection, activation of replication, an increase in the diversity of quasi-species and mutations of the virus, increased apoptosis of hepatocytes, suppression of the host's immune response, an increase in steatosis and iron levels in the liver are noted. All this leads to the rapid development of the disease, the high incidence of CP C and HCC, and the low effectiveness of interferon therapy. The effectiveness of AVT in chronic hepatitis C in people who drink alcohol is 3 times lower than the standard SVR indicators: with IFN monotherapy, SVR decreases to 7-8% compared to 25% in patients who do not drink alcohol; in combination therapy - up to 12-4% compared with 41%. There are no safe doses of alcohol for patients with chronic hepatitis C. It is recommended to completely stop taking it 6 months before the proposed AVT, which improves the results of antiviral treatment, but SVR does not reach the indicators characteristic of patients who did not drink alcohol in the past. Returning to alcohol intake after the end of AVT increases the risk of exacerbation of chronic hepatitis C and the return of viremia.

In patients with chronic hepatitis C at the stage of cirrhosis or in the presence of bridging fibrosis (F3), the risk of side effects of interferon therapy is higher than in less advanced stages of fibrosis. However, it has been shown that the frequency of their detection and the need to discontinue AVT do not differ significantly in groups of patients treated with pegylated IFN-α or IFN-α in the standard regimen. PEGylated IFN α-2a has a more pronounced myelosuppressive effect than IFN α-2b. Hematological toxicity with the use of pegylated IFN α appears in the first 4 weeks of treatment, then a stable level of leukocytes and platelets is reached. Especially quickly their number decreases after the first dose of drugs. AVT is prescribed for patients with compensated cirrhosis C with a level of leukocytes of 3000/mmYo and platelets of 50,000/mmYo. With a decrease in the level of neutrophils to 600/mmЁ, and the level of platelets to 20,000/mmЁ, IFN-α is canceled.

Modification of the dose of pegylated IFN-α or ribavirin (dose reduction or discontinuation of the drug) due to side effects was noted in 50% of patients with LC C. Depending on the achievement of an early virological response at the 12th week of treatment, various treatment options for LC C were proposed: continued combination therapy in the most effective doses for 36 weeks upon reaching an early virological response; treatment with low doses of pegylated IFN α-2b (0.5 µg/kg) for 5 years in the absence of such a response at week 4 (EPIC3) or low doses of pegylated IFN α-2a (90 µg) for 4 years (HALT -WITH).

Indications for repeated courses of AVT have been determined: the presence of HCV genotypes 2 or 3; partial response in the previous course of AVT, F3- and F4-stages of fibrosis. Contraindications to repeated courses of treatment are: advanced age, genotype 1, cirrhosis C with hyperbilirubinemia, high viral load, high body mass index, minimal changes in the liver on biopsy (HAI less than 4 points), and continued use of alcohol or drugs.

Thus, AVT of compensated and decompensated cirrhosis in chronic hepatitis C solves a number of the following tasks: slowing down the decompensation of cirrhosis, reducing mortality from its complications (bleeding from varicose veins, hepatocellular insufficiency, etc.), preventing the development of HCC and preventing infection reactivation after liver transplantation, as well as improving the quality of life of patients and ensuring their social rehabilitation. Undoubtedly, in the early stages of HCV infection, AVT gives the best results: the SVR rate in the treatment of acute hepatitis C reaches 90%, hCG - 60-70%, which exceeds the effectiveness of treatment of cirrhosis with pegylated IFN-α and ribavirin (30-50%) . Our experience with AVT of chronic hepatitis C with a low degree of activity allows us to speak about the high efficiency of treatment in this category of patients. Using pegylated IFN α-2b (1.5 μg/kg) and ribaverin (more than 10.6 mg/kg) in the treatment of primary patients with a short disease duration (5.9±5.7 years), predominantly low degree of activity and weak fibrosis (F1), as well as low viral load, we received a sustained virological response in 86% of cases, including 77% of patients with HCV genotype 1, including 5 patients at the stage of cirrhosis C.

Literature

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12. Nikulkina E. N., Krel P. E., Lopatkina T. N. Combination therapy with peginterferon alfa-2b (pegintron) and ribavirin (Rebetol) in primary patients with chronic hepatitis C // Clinical Pharmacology and Therapy. - 2004. - No. 13 (2). - S. 48-52.

T. N. Lopatkina, Candidate of Medical Sciences, Associate Professor

MMA them. I. M. Sechenov, Moscow

Hepatitis C is an inflammatory liver disease, it develops under the influence of the hepatitis C virus. An effective vaccine that could protect against this virus simply does not yet exist in nature, and it will not appear soon.

It is of two types - acute and chronic. In 20% of cases, people with acute hepatitis have a good chance to recover, and in 80% the patient's body is not able to overcome the virus itself and the disease becomes chronic.

Transmission of the virus occurs through infection through the blood. Today in the world there are 150 million people who are carriers of chronic hepatitis C, and every year hepatitis ends with a fatal outcome in 350 thousand patients.

In general, the first symptoms of hepatitis C appear 30-90 days after infection. That is why if you feel unwell, apathy, fatigue and other phenomena that are unusual for your body, then you better consult a doctor. This is necessary in order for the doctor to make an accurate diagnosis, and based on it choose the most effective treatment.

How is hepatitis C transmitted?

What it is? Infection occurs mainly through contact with the blood of an infected person. Hepatitis C is also transmitted during medical procedures: blood collection and transfusion, surgical operations, manipulations at the dentist.

The source of infection can be manicure tools, tattoo machines, needles, scissors, razors, etc. If the skin or mucous membranes are broken, contact with the blood of an infected person can result in infection.

Rarely, hepatitis C is transmitted through sexual contact. Infected pregnant women are at risk that the baby at birth is also infected with the virus.

The most difficult to tolerate the course of the virus:

• alcohol abusers.
• persons suffering from other chronic liver diseases, including others.
• older people and children.

Hepatitis C disease is not transmitted in household contacts through hugs, handshakes, with this disease you can use common dishes and towels, but you can not use shared personal hygiene items (razors, nail scissors, toothbrushes). The transmission mechanism of the disease is only hematogenous.

Hepatitis C Symptoms

In most situations, viral hepatitis C proceeds slowly, without pronounced symptoms, remaining undiagnosed for years and manifesting itself already with significant destruction of liver tissue. Often, patients are diagnosed with hepatitis C for the first time when they already have or hepatocellular liver cancer.

The incubation period of hepatitis lasts from 1 to 3 months. Even after the end of this period, the virus may not manifest itself in any way until liver damage becomes too obvious.

After infection, 10-15% of patients self-heal, the remaining 85-90% develop primary chronic hepatitis C without any specific symptoms (such as pain, jaundice, etc.). And only in rare cases, patients develop an acute form with jaundice and severe clinical manifestations, which, with adequate therapy, leads to a complete cure of the patient from hepatitis C.

The first signs of hepatitis C in women and men

For a long time, the symptoms practically do not bother patients. In the acute period, the disease manifests itself only by weakness, fatigue, sometimes proceeds under the guise of a respiratory viral infection with pain in the muscles and joints. These may be the first signs of hepatitis C in women or men.

Jaundice and any clinical manifestations of hepatitis develop in a very small percentage of those infected (the so-called icteric form of the disease). And this is actually excellent - patients immediately turn to specialists, and the disease has time to be cured.

However, the majority of those infected carry hepatitis C on their feet: with an anicteric form, they either do not notice anything at all, or they attribute the malaise to a cold.

chronic hepatitis

A feature of chronic hepatitis C is a latent or asymptomatic course for many years, usually without jaundice. , detection of anti-HCV and HCV RNA in the blood serum for at least 6 months are the main signs of chronic hepatitis C. Most often, this category of patients is discovered by chance, during examination before surgery, during medical examination, etc.

The course of chronic hepatitis C may be accompanied by such immune-mediated extrahepatic manifestations as mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, tardive cutaneous porphyria,.

A photo

In the photo, liver damage with a long course of hepatitis.

Forms

By the presence of jaundice in the acute phase of the disease:

1. Icteric.
2. Anicteric.

According to the duration of the flow.

1. Acute (up to 3 months).
2. Protracted (more than 3 months).
3. Chronic (more than 6 months).

By gravity.

1. Easy.
2. Medium heavy.
3. Heavy.
4. Fulminant.

Complications.

1. Hepatic coma.

1. Recovery.
2. chronic hepatitis C.
3. Cirrhosis of the liver.
4. Hepatocellular carcinoma.

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

stages

The disease is divided into several stages, depending on which treatment is prescribed.

1. Acute - it is characterized by an asymptomatic course. A person often does not suspect that he is a carrier of the virus and the source of infection.
2. Chronic - in the vast majority of cases (about 85%), after the acute stage, the chronic course of the disease begins.
3. Cirrhosis of the liver - develops with further progression of the pathology. This is a severe disease that threatens the patient's life both in itself and in the fact that if it is present, the risk of developing other complications, in particular, liver cancer, increases significantly.

A distinctive feature of the virus is the ability to genetic mutations, as a result of which approximately 40 HCV subspecies can be simultaneously detected in the human body (within one genotype).

Virus genotypes

The severity and course of the disease depend on the hepatitis C genotype that infected the body. Six genotypes with several subtypes are known so far. Most often, viruses of 1, 2 and 3 genotypes are found in the blood of patients. They cause the most pronounced manifestations of the disease.

In Russia, the most common genotype is 1b. Less often - 3, 2 and 1a. Hepatitis C caused by the genotype 1b virus is characterized by a more severe course.

Diagnosis of hepatitis

The main method for diagnosing hepatitis is to determine the presence of antibodies to hepatitis C virus (anti-HCV) and HCV-RNA. Positive results from both tests confirm the presence of infection. The presence of IgM antibodies (anti-HCV IgM) makes it possible to distinguish active hepatitis from carriage (when there are no IgM antibodies and ALT is normal).

A PCR test for hepatitis C (polymerase chain reaction) allows you to determine the presence of hepatitis C RNA in the patient's blood. PCR is mandatory for all patients with suspected viral hepatitis. This method is effective from the first days of infection and plays an important role in early diagnosis.

When is hepatitis C more difficult to treat?

According to statistics, hepatitis C is more difficult to treat in men, people over 40 years of age, in patients with normal transaminase activity, with a high viral load, in those with 1b genotype of the virus. Of course, the presence of cirrhosis of the liver at the time of treatment worsens the prognosis.

The effectiveness of antiviral treatment depends on many factors. With a long course of hepatitis C, it is not easy to achieve complete eradication of the virus. The main task is to slow down the process of active reproduction of viruses.

This is possible in most cases with the use of modern antiviral therapy regimens. In the absence of active reproduction of viruses in the liver, the severity of inflammation significantly decreases, fibrosis does not progress.

Hepatitis C treatment

In the case of hepatitis C, combination therapy with interferon-alpha and ribavirin is considered the standard of care. The first drug is available as a solution for subcutaneous injection under the trademarks Pegasys® (Pegasys®), PegIntron® (PegIntron®). Peginterferons are taken once a week. Ribavirin is available under various brand names and is taken as a tablet twice a day.

1. Interferon-alpha is a protein that the body synthesizes on its own in response to a viral infection, i.e. it is actually a component of natural antiviral protection. In addition, interferon-alpha has antitumor activity.
2. Ribavirin as an independent treatment has low efficiency, but when combined with interferon, it significantly increases its effectiveness.

The duration of therapy can be from 16 to 72 weeks, depending on the genotype of the hepatitis C virus, the response to treatment, which is largely associated with the individual characteristics of the patient, which are determined by his genome.

A course of antiviral therapy using the "gold standard" can cost a patient from $5,000 to $30,000, depending on the choice of drugs and treatment regimen. The main costs are for interferon preparations. Foreign-made pegylated interferons are more expensive than conventional interferons from any manufacturer.

In most regions of Russia, treatment is not covered by compulsory medical insurance and is carried out at the expense of regional programs. For example, in Moscow alone, up to 2,000,000,000 rubles are annually spent on the treatment of people with hepatitis C, treating up to 1,500 patients a year. At the same time, 70,000 patients are officially registered in Moscow. It turns out that it will take 50 years to cure them all.

In addition to standard therapy, in 2018, patients with chronic hepatitis C who are not at high risk of death from other causes are recommended to receive interferon-free direct-acting antiviral drugs (DAA) for 8 to 24 weeks. Patients at high risk of complications (assessed by degree of liver damage) should be considered first. Currently, interferon-free AVT regimens use inhibitors of replication of three nonstructural HCV proteins: NS3/4A protease, NS5A interferon-resistant protein, and NS5B polymerase.

The effectiveness of hepatitis C treatment is assessed by blood biochemical parameters (decrease in transaminase activity) and the presence of HCV-RNA, by reducing the level of viral load.

New in hepatitis treatment

Although AbbVie Inc., which consists of the second-generation NS3 and NS5A viral protein inhibitors glecaprevir/pibrentasvir, received FDA approval on August 3, 2017, the final phase 3 clinical trials of select Maviret-based regimens are still ongoing and will continue until 2019 In particular, the optimal duration of glecaprevir/pibrentasvir therapy for acute hepatitis C is being established, and the combination of glecaprevir/pibrentasvir and sofosbuvir is being investigated as a “last resort” therapy for people with multidrug resistance.

The first pangenotypic representatives of the class of non-nucleoside inhibitors of NS5B polymerase GSK2878175 and CC-31244 are undergoing phase I-II clinical trials. Both inhibitors can potentially be used in combination therapy with both other classes of DAAs and indirect antiviral drugs.

Maviret was officially registered with the Ministry of Health of the Russian Federation on April 13, 2018, after which it appeared in pharmacies. The average cost of a package of "Mavyret" exceeds 350 thousand rubles, and the price of a standard 8-week course of treatment reaches 600-700 thousand rubles or more.

It is worth noting that the standards of care for people with hepatitis C are changing rapidly. Sofosbuvir, daclatasvir and the sofosbuvir/ledipasvir combination are among the regimens favored by the WHO guidelines and can achieve cure rates of 95%.

Side effects of antiviral therapy

If treatment with interferons is indicated, then side effects cannot be avoided, but they are predictable.

After the first injections of interferon, most people experience a syndrome. After 2-3 hours, the temperature rises to 38-39 0 C, there may be chills, pain in the muscles and joints, noticeable weakness. The duration of this state can be from several hours to 2-3 days. Within 30 days, the body is able to get used to the introduction of interferon, so by this time the flu-like syndrome disappears. Weakness and fatigue persist, but this has to be tolerated.

As for Ribavirin, it is usually well tolerated. But quite often in the general analysis of blood, the phenomena of mild hemolytic anemia are noted. There may be symptoms of mild dyspepsia, rarely headache, increased levels of uric acid in the blood, very rarely there is intolerance to the drug.

How long do people live with hepatitis C if left untreated?

It is very difficult to say unequivocally how many people live with hepatitis C, just like with HIV infection. In an average number of patients, cirrhosis of the liver can develop in about 20-30 years.

As a percentage, depending on the person's age, cirrhosis develops:

• in 2% of patients infected before the age of 20;
• in 6% of those who received the virus at the age of 21-30 years;
• in 10% of those infected at the age of 31-40;
• in 37% of patients at the age of 41-50;
• in 63% of those infected over 50 years of age.

Also, most studies have shown that the development of fibrosis depends on gender. In men, this pathology develops much faster and in a more severe form, even if treated.

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

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 a predominant inflammatory lesion of the liver and intoxication syndrome. Most often, hepatitis can be caused by hepatitis viruses: A, B, C, D, G, E, TTV, Sen, etc. Cytomegalovirus, Epstein-Barr virus, etc. also contribute to the development of hepatitis. The listed hepatitis viruses cause acute viral hepatitis, and the virus Epstein-Barr causes infectious mononucleosis, which also causes inflammation of the liver. Acute hepatitis B, B + D, C are chronic, can progress to liver cirrhosis and lead to the development of cancer of various localization, thus significantly reducing a person's life expectancy.

True, 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: the number of patients with cirrhosis of the liver, liver cancer, cancer of the pancreas, kidney, uterus - diseases that occur with the assistance of the hepatitis C virus have recently increased significantly. Mortality from hepatitis C in the next 5 years increased by 2.5 times. Ten-year survival of patients with cirrhosis of the liver is about 50%. The danger of the hepatitis C virus lies in the fact that it is characterized by a primary chronic course without jaundice with a minimal list of clinical symptoms. That is why patients do not seek medical help before the development of irreversible complications, since in fact the disease is steadily progressing. Hepatitis C is diagnosed most often by accident or with the onset of symptoms at stages 2-4 of liver fibrosis, or already at the transition of hepatitis to cirrhosis of the liver. These changes are irreversible, as liver failure progresses, disorders of brain function (encephalopathy), kidney function (hepatorenal syndrome) and blood clotting disorders (bleeding) join, from which the patient dies.

Where and how can one get 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, 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 use used injection needles and those who received blood transfusions prior to 1987 are at the highest risk of becoming infected with the hepatitis C virus. Intermediate (medium-increased) risk of HCV is in patients on hemodialysis (artificial kidney machine), persons who received organ transplants (transplantation) or who received blood transfusions before 1992, and all those who, for health reasons, received blood from donor, and then tested positive for HCV markers, persons with liver disease of unknown cause, infants born to HCV-infected mothers. The next category (increased risk) includes medical workers who come into contact with the blood of a patient infected with the HS virus, people who have sex with many partners, or with one infected partner, people who often perform manicure, pedicure, piercing, tattooing, shaving with possible damage to the skin, which are serviced in salons where the staff does not follow the rules of asepsis and antisepsis, and reusable instruments are not properly sterilized. People in all risk groups for hepatitis C should be tested for HCV markers and vaccinated against hepatitis B, as they are at risk of contracting this infection too.

Why is the number of patients with hepatitis C increasing at such a rapid pace? Apart from the lack of a vaccine, what else is causing this? Is there an epidemic of hepatitis C?

The main reason for the continuous spread of viral hepatitis is insufficient sanitary and epidemiological supervision to ensure that private institutions (hairdressing salons, dental offices, etc.) comply with the rules of asepsis, antisepsis, 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, mass media, demonstrating unofficial statistics on the infection of the population and the incidence of viral hepatitis, unanimously speak of an “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 which 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 for the funds allocated under the quota for the Chernivtsi region as part of the implementation of the National Program to Combat Viral Hepatitis, as well as the funds of the Regional Program of the Department of Health, about 500 people are registered. The regional sanitary and epidemiological station maintains a register of all patients, they are examined in public and private laboratories, medical institutions of the city and the region, and these data, of course, are more accurate.

Who gets hepatitis? Are they socially unprotected segments of the population or are they quite prosperous people?

Persons of various social groups are ill. First of all, these are injecting drug users, HIV-infected and AIDS patients often co-infected with the hepatitis C or B virus, persons who received transfusions of non-quarantined hepatitis C virus blood or underwent surgery for health reasons with non-sterile instruments (in the ATO zone), patients chronic kidney disease stage 5, constantly undergoing hemodialysis procedures, persons leading an immoral lifestyle with frequent change of sexual partners, or with unknown persons in recreational areas, or a regular partner with chronic viral hepatitis C, as well as all those persons indicated in risk groups of accidental HCV infection in beauty salons, private dental offices in conditions of careless use of non-sterile instruments by specialists.

How to prevent hepatitis C infection? Is there any 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 if you have been there before, a risk group with an 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 soon it will be introduced into the practice of healthcare.

Hepatitis C is said to be a "soft" killer. Is the course of the disease almost asymptomatic? What early symptoms of the disease make it possible to suspect 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 they may be disguised as influenza, SARS, food poisoning. Manifestations of infection can generally be detected only when hepatitis passes 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, blood vessels, heart, kidneys, blood (anemia), joint diseases, and HCV is detected during the examination .

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

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

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

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

Can hepatitis C be cured?

Despite the fact that at one time there was a large number of refusals of vaccinations against hepatitis B, and now there is a shortage of the vaccine, 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 in both hepatitis are the same, parenteral, sexual, vertical (from mother to fetus) infection mechanisms are also the same. If the awareness of the population about the importance of vaccination does not increase and the instinct of self-preservation does not work (to protect oneself from risk factors), and the conscience of those service workers whose negligent attitude contributes to an increase in the prevalence of viral hepatitis does not appear, the situation will worsen significantly.

Hundreds of suppliers bring hepatitis C medicines from India to Russia, but only M-PHARMA will help you buy sofosbuvir and daclatasvir, while professional consultants will answer any of your questions throughout the therapy.

Hepatitis is called acute and chronic inflammatory diseases of the liver, which are not focal, but widespread. Different hepatitis has different methods of infection, they also differ in the rate of progression of the disease, clinical manifestations, methods and prognosis of therapy. Even the symptoms of different types of hepatitis are different. Moreover, some symptoms are more pronounced than others, which is determined by the type of hepatitis.

Main Symptoms

1. Jaundice. The symptom is common and is due to the fact that bilirubin enters the patient's blood during liver damage. Blood, circulating through the body, carries it through the organs and tissues, staining them yellow.
2. The appearance of pain in the region of the right hypochondrium. It occurs due to an increase in the size of the liver, leading to the appearance of pain, which is dull and prolonged, or is paroxysmal in nature.
3. Deterioration of well-being, accompanied by fever, headaches, dizziness, indigestion, drowsiness and lethargy. All this is a consequence of the action on the body of bilirubin.

Hepatitis acute and chronic

Hepatitis in patients have acute and chronic forms. In an acute form, they appear in the case of viral liver damage, as well as if there has been poisoning with various types of poisons. In acute forms of the course of the disease, the condition of patients deteriorates rapidly, which contributes to the accelerated development of symptoms.

With this form of the disease, favorable prognosis is quite possible. Except for its transformation into a chronic one. In the acute form, the disease is easily diagnosed and easier to treat. Untreated acute hepatitis easily develops into a chronic form. Sometimes with severe poisoning (for example, alcohol), the chronic form occurs on its own. In the chronic form of hepatitis, the process of replacement of liver cells with connective tissue occurs. It is weakly expressed, goes slowly, and therefore sometimes remains undiagnosed until the onset of cirrhosis of the liver. Chronic hepatitis is treated worse, and the prognosis for its cure is less favorable. In the acute course of the disease, the state of health worsens significantly, jaundice develops, intoxication appears, the functional work of the liver decreases, and the content of bilirubin in the blood increases. With timely detection and effective treatment of acute hepatitis, the patient most often recovers. With a duration of the disease for more than six months, hepatitis becomes chronic. The chronic form of the disease leads to serious disorders in the body - the spleen and liver increase, metabolism is disturbed, complications arise in the form of cirrhosis of the liver and oncological formations. If the patient has reduced immunity, the treatment regimen is chosen incorrectly, or there is alcohol dependence, then the transition of hepatitis to a chronic form threatens the patient's life.

Varieties of hepatitis

Hepatitis has several types: A, B, C, D, E, F, G, they are also called viral hepatitis, since the cause of their occurrence is a virus.

Hepatitis A

This type of hepatitis is also called Botkin's disease. It has an incubation period ranging from 7 days to 2 months. Its causative agent - an RNA virus - can be transmitted from a sick person to a healthy person with the help of poor-quality products and water, contact with household items used by the patient. Hepatitis A is possible in three forms, they are divided according to the strength of the manifestation of the disease:

• in the acute form with jaundice, the liver is seriously damaged;
• with subacute without jaundice, we can talk about a milder version of the disease;
• in the subclinical form, you may not even notice symptoms, although the infected person is a source of the virus and is able to infect others.

Hepatitis B

This disease is also called serum hepatitis. Accompanied by an increase in the liver and spleen, the appearance of pain in the joints, vomiting, temperature, liver damage. It proceeds either in acute or in chronic forms, which is determined by the state of the patient's immunity. Ways of infection: during injections with violation of sanitary rules, sexual contacts, during blood transfusion, use of poorly disinfected medical instruments. The duration of the incubation period is 50 ÷ 180 days. The incidence of hepatitis B is reduced by the use of vaccination.

Hepatitis C

This type of disease is one of the most serious diseases, as it is often accompanied by cirrhosis or liver cancer, which subsequently leads to death. The disease is difficult to treat, and moreover, having had hepatitis C once, a person can be re-infected with the same disease. It is not easy to cure HCV: after contracting hepatitis C in an acute form, 20% of the sick people recover, and in 70% of patients the body is not able to recover from the virus on its own, and the disease becomes chronic. It has not yet been possible to establish the reason why some heal themselves, while others do not. The chronic form of hepatitis C will not disappear on its own, and therefore needs therapy. Diagnosis and treatment of the acute form of HCV is carried out by an infectious disease specialist, the chronic form of the disease - by a hepatologist or gastroenterologist. You can become infected during a transfusion of plasma or blood from an infected donor, using poorly processed medical instruments, sexually, and a sick mother transmits the infection to her child. The hepatitis C virus (HCV) is rapidly spreading around the world, the number of patients has long ago exceeded one and a half hundred million people. Previously, HCV was difficult to treat, but now the disease can be cured using modern direct-acting antivirals. Only this therapy is quite expensive, and therefore not everyone can afford it.

Hepatitis D

This type of hepatitis D is possible only with co-infection with the hepatitis B virus (co-infection is a case of infection of one cell with viruses of different types). It is accompanied by massive liver damage and an acute course of the disease. Ways of infection - the entry of a disease virus into the blood of a healthy person from a virus carrier or a sick person. The incubation period lasts 20 ÷ 50 days. Outwardly, the course of the disease resembles hepatitis B, but its form is more severe. May become chronic, then progressing to cirrhosis. It is possible to carry out a vaccination similar to that used for hepatitis B.

Hepatitis E

Slightly resembles hepatitis A in its course and transmission mechanism, since it is also transmitted through the blood in the same way. Its feature is the occurrence of fulminant forms that cause death in a period not exceeding 10 days. In other cases, it can be effectively cured, and the prognosis for recovery is most often favorable. An exception may be pregnancy, as the risk of losing a child approaches 100%.

Hepatitis F

This type of hepatitis has not yet been studied enough. It is only known that the disease is caused by two different viruses: one was isolated from the blood of donors, the second was found in the feces of a patient who received hepatitis after a blood transfusion. Signs: the appearance of jaundice, fever, ascites (accumulation of fluid in the abdominal cavity), an increase in the size of the liver and spleen, an increase in the levels of bilirubin and liver enzymes, the occurrence of changes in the urine and feces, as well as general intoxication of the body. Effective methods of therapy for hepatitis F have not yet been developed.

Hepatitis G

This type of hepatitis is similar to hepatitis C, but is not as dangerous as it does not contribute to cirrhosis and liver cancer. Cirrhosis can occur only in case of co-infection of hepatitis G and C.

Diagnostics

Viral hepatitis in their symptoms are similar to one another, just like some other viral infections. For this reason, it is difficult to accurately diagnose the patient. Accordingly, to clarify the type of hepatitis and the correct prescription of therapy, laboratory blood tests are required to identify markers - indicators that are individual for each type of virus. By identifying the presence of such markers and their ratio, it is possible to determine the stage of the disease, its activity and possible outcome. In order to track the dynamics of the process, after a period of time, the surveys are repeated.

How is hepatitis C treated?

Modern regimens for the treatment of chronic forms of HCV are reduced to combined antiviral therapy, including direct-acting antivirals such as sofosbuvir, velpatasvir, daclatasvir, ledipasvir in various combinations. Ribavirin and interferons are sometimes added to enhance effectiveness. This combination of active ingredients stops the replication of viruses, saving the liver from their destructive effects. This therapy has a number of disadvantages:

1. The cost of medicines to fight the hepatitis virus is high, and not everyone can buy them.
2. Taking certain drugs is accompanied by unpleasant side effects, including fever, nausea, and diarrhea.

The duration of treatment for chronic forms of hepatitis takes from several months to a year, depending on the genotype of the virus, the degree of damage to the body and the drugs used. Because hepatitis C primarily affects the liver, patients are required to follow a strict diet.

Features of HCV genotypes

Hepatitis C is one of the most dangerous viral hepatitis. The disease is caused by an RNA virus called Flaviviridae. The hepatitis C virus is also called the "gentle killer". He received such an unflattering epithet due to the fact that at the initial stage the disease is not accompanied by any symptoms at all. There are no signs of classical jaundice, and there is no pain in the area of ​​the right hypochondrium. It is possible to detect the presence of the virus no earlier than a couple of months after infection. And before that, the reaction of the immune system is completely absent and it is impossible to detect markers in the blood, and therefore it is not possible to carry out genotyping. The peculiarity of HCV also includes the fact that after entering the blood during the process of reproduction, the virus begins to rapidly mutate. Such mutations prevent the infected person's immune system from adapting and fighting the disease. As a result, the disease can proceed without any symptoms for several years, after which cirrhosis or a malignant tumor appears almost immediately. Moreover, in 85% of cases, the disease from an acute form becomes chronic. The hepatitis C virus has an important feature - the diversity of the genetic structure. In fact, hepatitis C is a collection of viruses classified according to their structural variants and subdivided into genotypes and subtypes. The genotype is the sum of the genes encoding hereditary traits. So far, medicine knows 11 genotypes of the hepatitis C virus, which have their own subtypes. The genotype is indicated by numbers from 1 to 11 (although genotypes 1 ÷ 6 are mainly used in clinical studies), and subtypes, using the letters of the Latin alphabet:

• 1a, 1b and 1c;
• 2a, 2b, 2c and 2d;
• 3a, 3b, 3c, 3d, 3e and 3f;
• 4a, 4b, 4c, 4d, 4e, 4f, 4h, 4i and 4j;

In different countries, HCV genotypes are distributed differently, for example, in Russia it is most often found from the first to the third. The severity of the course of the disease depends on the variety of the genotype, they determine the treatment regimen, its duration and the result of treatment.

How are HCV strains spread around the world?

On the territory of the globe, hepatitis C genotypes are distributed heterogeneously, and most often you can find genotypes 1, 2, 3, and in some areas it looks like this:

• in Western Europe and its eastern regions, genotypes 1 and 2 are most common;
• in the USA, subtypes 1a and 1b;
• in northern Africa, genotype 4 is the most common.

At risk of possible HCV infection are people with blood diseases (tumors of the hematopoietic system, hemophilia, etc.), as well as patients who are being treated in dialysis units. Genotype 1 is considered the most common in the countries of the world - it accounts for ~ 50% of the total number of cases. In second place in terms of prevalence is genotype 3 with an indicator of slightly more than 30%. The distribution of HCV across the territory of Russia has significant differences from the world or European variants:

• genotype 1b accounts for ~50% of cases;
• for genotype 3a ~20%,
• ~10% of patients are infected with hepatitis 1a;
• genotype 2 hepatitis was found in ~5% of those infected.

But the difficulties of HCV therapy depend not only on the genotype. The following factors also influence the effectiveness of treatment:

• age of patients. The chance of a cure in young people is much higher;
• it is easier for women to recover than for men;
• the degree of liver damage is important - the favorable outcome is higher with less damage to it;
• the magnitude of the viral load - the less viruses in the body at the time of the start of treatment, the more effective the therapy;
• patient's weight: the higher it is, the more complicated the treatment.

Therefore, the treatment regimen is chosen by the attending physician, based on the above factors, genotyping and EASL recommendations (European Association for Liver Diseases). EASL constantly keeps its recommendations up to date and, as new effective drugs for the treatment of hepatitis C appear, adjusts the recommended treatment regimens.

Who is at risk for HCV infection?

As you know, the hepatitis C virus is transmitted through the blood, and therefore the most likely to become infected can:

• patients receiving blood transfusions;
• patients and clients in dental offices and medical facilities where medical instruments are improperly sterilized;
• due to non-sterile instruments, it can be dangerous to visit a nail and beauty salon;
• lovers of piercings and tattoos can also suffer from poorly processed tools,
• high risk of infection in those who use drugs due to repeated use of non-sterile needles;
• the fetus can become infected from a mother infected with hepatitis C;
• during sexual intercourse, the infection can also enter the body of a healthy person.

How is hepatitis C treated?

The hepatitis C virus was not in vain considered a “gentle” killer virus. It is able to not manifest itself for years, after which it suddenly shows up in the form of complications accompanied by cirrhosis or liver cancer. But more than 177 million people in the world have been diagnosed with HCV. The treatment, which was used until 2013, combining injections of interferon and ribavirin, gave patients a chance of healing that did not exceed 40-50%. And besides, it was accompanied by serious and painful side effects. The situation changed in the summer of 2013 after the US pharmaceutical giant Gilead Sciences patented the substance sofosbuvir, produced as a drug under the Sovaldi brand, which included 400 mg of the drug. It became the first direct-acting antiviral drug (DAA) designed to combat HCV. The results of clinical trials of sofosbuvir pleased physicians with the effectiveness, which, depending on the genotype, reached 85 ÷ 95%, while the duration of the course of therapy was more than halved compared to treatment with interferons and ribavirin. And, although the pharmaceutical company Gilead patented sofosbuvir, it was synthesized in 2007 by Michael Sophia, an employee of Pharmasett, subsequently acquired by Gilead Sciences. From the name of Michael, the substance he synthesized was named sofosbuvir. Michael Sophia himself, together with a group of scientists who made a number of discoveries that revealed the nature of HCV, which made it possible to create an effective drug for its treatment, received the Lasker-DeBakey Award for Clinical Medical Research. Well, almost all the profit from the sale of a new effective tool went to Gilead, which set monopoly high prices for Sovaldi. Moreover, the company protected its development with a special patent, according to which Gilead and some of its partner companies became the owners of the exclusive right to manufacture the original DAA. As a result, Gilead's profits in the first two years of marketing the drug many times overcame all the costs that the company incurred to acquire Pharmasett, obtain a patent and subsequent clinical trials.

What is Sofosbuvir?

The effectiveness of this drug in the fight against HCV was so high that now almost no therapy regimen can do without its use. Sofosbuvir is not recommended for use as monotherapy, but with complex use it shows exceptionally good results. Initially, the drug was used in combination with ribavirin and interferon, which allowed in uncomplicated cases to achieve a cure in just 12 weeks. And this despite the fact that therapy with only interferon and ribavirin was half as effective, and its duration sometimes exceeded 40 weeks. After 2013, each subsequent year brought news of the emergence of more and more new drugs that successfully fight the hepatitis C virus:

• daclatasvir appeared in 2014;
• 2015 was the birth year of ledipasvir;
• 2016 pleased with the creation of velpatasvir.

Daclatasvir was released by Bristol-Myers Squibb as Daklinza, containing 60 mg of the active ingredient. The next two substances were created by Gilead scientists, and since neither of them was suitable for monotherapy, drugs were used only in combination with sofosbuvir. To facilitate therapy, Gilead prudently released the newly created drugs immediately in combination with sofosbuvir. So there were drugs:

• Harvoni, a combination of sofosbuvir 400 mg and ledipasvir 90 mg;
• Epclusa, which included sofosbuvir 400 mg and velpatasvir 100 mg.

In therapy with daclatasvir, Sovaldi and Daklinz had to take two different drugs. Each of the paired combinations of active substances was used to treat certain HCV genotypes according to the treatment regimens recommended by EASL. And only the combination of sofosbuvir with velpatasvir turned out to be a pangenotypic (universal) remedy. Epclusa cured all hepatitis C genotypes with almost the same high efficiency of approximately 97 ÷ 100%.

The emergence of generics

Clinical trials confirmed the effectiveness of the treatment, but all these highly effective drugs had one significant drawback - too high prices that did not allow them to be purchased by the bulk of the sick. The monopoly high prices for products set by Gilead caused outrage and scandals, which forced patent holders to make certain concessions by granting licenses to some companies from India, Egypt and Pakistan to produce analogues (generics) of such effective and popular drugs. Moreover, the fight against patent holders offering medicines for treatment at biased prices was led by India, as a country in which millions of chronic hepatitis C patients live. As a result of this struggle, Gilead issued licenses and patent developments to 11 Indian companies for the independent production of first sofosbuvir, and then its other new drugs. Having received licenses, Indian manufacturers quickly set up the production of generics, assigning their own trade names to the manufactured drugs. This is how Sovaldi generics first appeared, then Daklinza, Harvoni, Epclusa, and India became the world leader in their production. Indian manufacturers, under a license agreement, pay 7% of their earnings to the patent holders. But even with these payments, the cost of generics produced in India turned out to be ten times less than that of the originals.

Mechanisms of action

As previously reported, new HCV therapies that have emerged are classified as DAAs and act directly on the virus. Whereas previously used for treatment, interferon with ribavirin strengthened the human immune system, helping the body to resist the disease. Each of the substances acts on the virus in its own way:

1. Sofosbuvir blocks RNA polymerase, thereby inhibiting the replication of the virus.

1. Daclatasvir, ledipasvir and velpatasvir are NS5A inhibitors that interfere with the spread of viruses and their entry into healthy cells.

Such a targeted effect makes it possible to successfully fight HCV by using sofosbuvir paired with daklatasvir, ledipasvir, velpatasvir for therapy. Sometimes, to enhance the effect on the virus, a third component is added to the pair, which is most often ribavirin.

Generic manufacturers from India

The pharmaceutical companies of the country have taken advantage of the licenses granted to them, and now India produces the following Sovaldi generics:

• Hepcvir is manufactured by Cipla Ltd.;
• Hepcinat - Natco Pharma Ltd.;
• Cimivir - Biocon ltd. & Hetero Drugs Ltd.;
• MyHep is a manufacturer of Mylan Pharmaceuticals Private Ltd.;
• SoviHep - Zydus Heptiza Ltd.;
• Sofovir is the manufacturer of Hetero Drugs Ltd.;
• Resof - manufactured by Dr Reddy's Laboratories;
• Virso - Releases Strides Arcolab.

Analogues of Daklinza are also made in India:

• Natdac from Natco Pharma;
• Dacihep by Zydus Heptiza;
• Daclahep from Hetero Drugs;
• Dactovin by Strides Arcolab;
• Daclawin by Biocon ltd. & Hetero Drugs Ltd.;
• Mydacla by Mylan Pharmaceuticals.

Following Gilead, Indian drug manufacturers also mastered the production of Harvoni, resulting in the following generics:

• Ledifos - releases Hetero;
• Hepcinat LP - Natco;
• Myhep LVIR - Mylan;
• Hepcvir L - Cipla Ltd.;
• Cimivir L - Biocon ltd. & Hetero Drugs Ltd.;
• LadyHep - Zydus.

And already in 2017, the production of the following Indian generics of Epclusa was mastered:

• Velpanat was released by Natco Pharma;
• the release of Velasof was mastered by Hetero Drugs;
• SoviHep V was launched by Zydus Heptiza.

As you can see, Indian pharmaceutical companies do not lag behind American manufacturers, quickly mastering their newly developed drugs, while observing all the qualitative, quantitative and medicinal characteristics. Withstanding including pharmacokinetic bioequivalence in relation to the originals.

Requirements for generics

A generic drug is called a drug that, according to its main pharmacological properties, can replace the treatment with expensive original drugs with a patent. They can be released both with and without a license, only its presence makes the produced analogue licensed. In the case of issuing a license to Indian pharmaceutical companies, Gilead also provided them with the production technology, giving license holders the right to an independent pricing policy. In order for an analogue of a medicinal product to be considered a generic, it must meet a number of parameters:

1. It is necessary to observe the ratio of the most important pharmaceutical components in the preparation in terms of qualitative as well as quantitative standards.

1. Compliance with the relevant international standards should be adhered to.

1. Mandatory observance of appropriate production conditions is required.

1. The preparations should maintain an appropriate equivalent of the absorption parameters.

It is worth noting that WHO is on guard for ensuring the availability of medicines, seeking to replace expensive branded medicines with the help of budget generics.

Egyptian generics of sofosbuvir

Unlike India, Egyptian pharmaceutical companies have not become world leaders in the production of hepatitis C generics, although they have also mastered the production of sofosbuvir analogues. True, for the most part, the analogues they produce are unlicensed:

• MPI Viropack, manufactures Marcyrl Pharmaceutical Industries, one of the very first Egyptian generics;

• Heterosofir is manufactured by Pharmed Healthcare. Is an the only licensed generic in Egypt. On the packaging, under the hologram, there is a hidden code that allows you to check the originality of the drug on the manufacturer's website, thereby eliminating its fake;

• Grateziano, manufactured by Pharco Pharmaceuticals;

• Sofolanork, produced by Vimeo;

• Sofocivir manufactured by ZetaPhar.

Hepatitis Generics from Bangladesh

Bangladesh is another country with a large production of generic HCV drugs. Moreover, this country does not even require licenses for the production of analogues of branded medicines, since until 2030 its pharmaceutical companies are allowed to produce such medicines without having the appropriate license documents. The most famous and equipped with the latest technology is the pharmaceutical company Beacon Pharmaceuticals Ltd. The design of its production facilities was created by European specialists and meets international standards. Beacon markets the following generics for the treatment of hepatitis C virus:

• Soforal is a generic sofosbuvir containing 400 mg of active ingredient. Unlike traditional packs in bottles of 28 pieces, Soforal is produced in the form of blisters of 8 tablets in one plate;
• Daclavir is a generic of daclatasvir, one tablet of the drug contains 60 mg of the active ingredient. It is also released in the form of blisters, but each plate contains 10 tablets;
• Sofosvel is a generic Epclusa containing sofosbuvir 400mg and velpatasvir 100mg. Pangenotypic (universal) drug, effective in the treatment of HCV genotypes 1 ÷ 6. And in this case, there is no usual packaging in vials, the tablets are packed in blisters of 6 pieces in each plate.
• Darvoni is a complex drug that combines sofosbuvir 400 mg and daclatasvir 60 mg. If it is necessary to combine sofosbuvir therapy with daklatasvir, using drugs from other manufacturers, it is necessary to take a tablet of each type. And Beacon combined them into one pill. Packed Darvoni in blisters of 6 tablets in one plate, sent only for export.

When buying drugs from Beacon based on a course of therapy, you should take into account the originality of their packaging in order to purchase the amount necessary for treatment. The most famous Indian pharmaceutical companies As mentioned above, after obtaining licenses for the production of generic drugs for HCV therapy by the country's pharmaceutical companies, India has become a world leader in their production. But among the many companies, it is worth noting a few whose products are most famous in Russia.

Natco Pharma Ltd.

The most popular pharmaceutical company is Natco Pharma Ltd., whose drugs have saved the lives of several tens of thousands of patients with chronic hepatitis C. It has mastered the production of almost the entire line of direct-acting antiviral drugs, including sofosbuvir with daclatasvir and ledipasvir with velpatasvir. Natco Pharma appeared in 1981 in the city of Hyderabad with an initial capital of 3.3 million rupees, then the number of employees was 20 people. Natco currently employs 3,500 people in India at five Natco enterprises, and there are still branches in other countries. In addition to production units, the company has well-equipped laboratories that allow developing modern medicines. Among her own developments, it is worth noting drugs to combat cancer. One of the most famous drugs in this area is Veenat, produced since 2003 and used for leukemia. Yes, and the release of generics for the treatment of hepatitis C virus is a priority for Natco.

Hetero Drugs Ltd.

This company has set as its goal the production of generics, subordinating its own production network to this desire, including factories with affiliates and offices with laboratories. The production network of Hetero is focused on the production of medicines under licenses received by the company. One of its areas of activity is medicines that allow you to fight serious viral diseases, the treatment of which for many patients has become impossible due to the high cost of original drugs. The acquired license allows Hetero to quickly start producing generics, which are then sold at an affordable price for patients. The creation of Hetero Drugs dates back to 1993. Over the past 24 years, a dozen factories and several dozen production units have appeared in India. The presence of its own laboratories allows the company to carry out experimental work on the synthesis of substances, which contributed to the expansion of the production base and the active export of drugs to foreign countries.

Zydus Heptiza

Zydus is an Indian company with a vision to create a healthy society, which, according to its owners, will be followed by a change in the quality of life for people. The goal is noble, and therefore, to achieve it, the company conducts active educational activities that affect the poorest segments of the country's population. Including through free vaccination of the population against hepatitis B. Zidus is in fourth place in terms of output in the Indian pharmaceutical market. In addition, 16 of its drugs were included in the list of 300 essential medicines of the Indian pharmaceutical industry. Zydus products are in demand not only in the domestic market, they can be found in pharmacies in 43 countries of our planet. And the assortment of drugs produced at 7 enterprises exceeds 850 drugs. One of its most powerful productions is located in the state of Gujarat and is one of the largest not only in India, but also in Asia.

HCV Therapy 2017

Treatment regimens for hepatitis C for each patient are selected by the doctor individually. For the correct, effective and safe selection of the scheme, the doctor needs to know:

• virus genotype;
• the duration of the illness;
• the degree of liver damage;
• presence / absence of cirrhosis, concomitant infection (for example, HIV or other hepatitis), negative experience of previous treatment.

Having received this data after a cycle of tests, the doctor, based on the recommendations of EASL, chooses the best therapy option. The EASL recommendations are adjusted from year to year, new drugs are added to them. Before recommending new therapy options, they are submitted to Congress or a special meeting for consideration. In 2017, a special EASL meeting in Paris considered updates to the recommended schemes. The decision was made to completely discontinue the use of interferon therapy in the treatment of HCV in Europe. In addition, there is not a single recommended regimen using a single direct-acting drug. Here are some recommended treatment options. All of them are given for informational purposes only and cannot become a guide to action, since only a doctor can prescribe therapy, under whose supervision it will then take place.

1. Possible treatment regimens proposed by EASL in the case of hepatitis C monoinfection or co-infection with HIV + HCV in patients without cirrhosis and not previously treated:

• for treatment genotypes 1a and 1b can be used:

- sofosbuvir + ledipasvir, without ribavirin, duration 12 weeks; - sofosbuvir + daclatasvir, also without ribavirin, treatment period 12 weeks; - or sofosbuvir + velpatasvir without ribavirin, course duration 12 weeks.

• in therapy genotype 2 used without ribavirin for 12 weeks:

- sofosbuvir + dklatasvir; - or sofosbuvir + velpatasvir.

• during treatment genotype 3 without the use of ribavirin for a period of therapy of 12 weeks, use:

- sofosbuvir + daclatasvir; - or sofosbuvir + velpatasvir.

• in therapy genotype 4 you can use without ribavirin for 12 weeks:

sofosbuvir + ledipasvir; - sofosbuvir + daclatasvir; - or sofosbuvir + velpatasvir.

1. EASL recommended treatment regimens for hepatitis C monoinfection or co-infection with HIV/HCV in previously untreated patients with compensated cirrhosis:

• for treatment genotypes 1a and 1b can be used:

— sofosbuvir + ledipasvir with ribavirin, duration 12 weeks; - or 24 weeks without ribavirin; - and another option - 24 weeks with ribavirin with an unfavorable response prognosis; — sofosbuvir + daclatasvir, if without ribavirin, then 24 weeks, and with ribavirin, the treatment period is 12 weeks; - or sofosbuvir + velpatasvir without ribavirin, 12 weeks.

• in therapy genotype 2 apply:

— sofosbuvir + dklatasvir without ribavirin, the duration is 12 weeks, and with ribavirin, with an unfavorable prognosis, 24 weeks; - or sofosbuvir + velpatasvir without combination with ribavirin for 12 weeks.

• during treatment genotype 3 use:

- sofosbuvir + daclatasvir for 24 weeks with ribavirin; - or sofosbuvir + velpatasvir again with ribavirin, the treatment period is 12 weeks; - as an option, sofosbuvir + velpatasvir is possible for 24 weeks, but already without ribavirin.

• in therapy genotype 4 apply the same schemes as for genotypes 1a and 1b.

As you can see, in addition to the condition of the patient and the characteristics of his body, the combination of prescribed medications chosen by the doctor also influences the result of therapy. In addition, the duration of treatment depends on the combination chosen by the physician.

Treatment with modern HCV drugs

Take tablets of drugs of direct antiviral action as prescribed by a doctor orally once a day. They are not divided into parts, they are not chewed, but they are washed down with plain water. It is best to do this at the same time, so that a constant concentration of active substances in the body is maintained. It is not required to be tied to the timing of food intake, the main thing is not to do it on an empty stomach. Starting to take drugs, pay attention to how you feel, since during this period it is easiest to notice possible side effects. The DAAs themselves do not have a lot of them, but the drugs prescribed in the complex have much less. The most common side effects are:

• headaches;
• vomiting and dizziness;
• general weakness;
• loss of appetite;
• pain in the joints;
• a change in the biochemical parameters of the blood, expressed in a low level of hemoglobin, a decrease in platelets and lymphocytes.

Side effects are possible in a small number of patients. But all the same, all noticed ailments should be reported to the attending physician so that he can take the necessary measures. To avoid increased side effects, alcohol and nicotine should be excluded from consumption, as they have a harmful effect on the liver.

Contraindications

In some cases, taking DAAs is excluded, this applies to:

• individual hypersensitivity of patients to certain ingredients of medicines;

• patients under the age of 18, as there is no accurate data on their effects on the body;

• women who are pregnant and breastfeeding babies;

• women should use reliable methods of contraception to avoid conception during the period of therapy. Moreover, this requirement also applies to women whose partners are also undergoing DAA therapy.

Storage

Store antiviral drugs of direct action in places inaccessible to children and direct sunlight. The storage temperature should be in the range of 15 ÷ 30ºС. When you start taking medications, check their manufacturing and shelf life indicated on the package. Expired drugs should not be taken. How to buy DAAs for residents of Russia Unfortunately, it will not be possible to find Indian generics in Russian pharmacies. The pharmaceutical company Gilead, having granted licenses for the production of drugs, prudently banned their export to many countries. Including all European countries. Those who wish to purchase budget Indian generics for the fight against hepatitis C can use several ways:

• order them through Russian online pharmacies and receive the goods in a few hours (or days) depending on the place of delivery. Moreover, in most cases, even an advance payment is not required;
• order them through Indian online stores with home delivery. Here you will need an advance payment in foreign currency, and the waiting time will last from three weeks to a month. Plus, the need to communicate with the seller in English will be added;
• go to India and bring the drug yourself. This will also take time, plus the language barrier, plus the difficulty of verifying the originality of the goods purchased at the pharmacy. To everything else, the problem of self-exportation will be added, requiring a thermal container, a doctor's report and a prescription in English, as well as a copy of the receipt.

People interested in purchasing medicines decide for themselves which of the possible delivery options to choose. Just do not forget that in the case of HCV, a favorable outcome of therapy depends on the speed of its initiation. Here, in the literal sense, the delay of death is similar, and therefore you should not delay the beginning of the procedure.

Viral hepatitis C (HCV, HCV) occurs in all countries of the world. According to preliminary data, about 3% of the world's population (170 million) are infected with HCV. The highest prevalence of the disease is observed in the regions of Africa, East and Central Asia, as well as in the European Region and the Eastern Mediterranean Region. Infection prevalence rates in other regions range from 0.5% to 1%. Approximately 400,000 people die each year from viral hepatitis C.

A little about the hepatitis C virus

The hepatitis C virus is a complex RNA virus. A virus is considered complex, which is covered on the outside with an additional fat-soluble shell (supercapsid). The supercapsid gives the virus additional "strength".

The hepatitis C virus causes both acute and chronic forms of the disease (acute and chronic hepatitis). The acute form of viral hepatitis C is usually asymptomatic. In 85-90% of individuals who have suffered an acute form, the formation of a chronic form occurs. Individuals with chronic HCV have a 15–30% risk of developing liver cirrhosis within 20 years. Therefore, more often a person is diagnosed with a disease already in the later stages, which makes treatment difficult.

A structural feature of the hepatitis C virus genome is its high mutational variability (that is, the ability to constantly change its antigenic structure). This allows the pathogen to avoid the immune response and stay in the human body for a long time. Therefore, a vaccine has not yet been developed and a previous infection does not prevent new infections.

It was also noted that among the symptoms of the underlying disease (from the side of the liver), extrahepatic manifestations can also be observed. The latter occur, according to various sources, in 30-75% of patients. The role of HCV in the development of non-Hodgkin B-cell lymphoma, mixed cryoglobulinemia, idiopathic thrombocytopenia, glomerulonephritis, nephrotic syndrome, skin diseases, etc. has been established.

There are six genotypes (strains) of the virus, which in turn are divided into subtypes (1a and 1b). All genotypes of the HCV pathogen respond differently to treatment, which should be taken into account when starting therapy. The distribution of virus strains varies by region. In the post-Soviet space, 1 (mainly 1b), 2 and 3 HCV genotypes are most common. The prevalence of viral hepatitis C in the world, including its genotypes, is shown in the figure:

HCV treatment

As mentioned above, patients with viral hepatitis C are not so easy to identify. And in patients who managed to confirm the diagnosis, formed liver cirrhosis or hepatocellular carcinoma (primary liver cancer) is found, which significantly reduces the prognosis for a cure for the disease.

The acute form of HCV is very rarely associated as a life-threatening disease for the patient. According to WHO statistics, about 15% of infected individuals are spontaneously cured within six months from the moment of infection without the use of any treatment. In the rest of the people, as mentioned above, a chronic form of HCV is formed. As a result, viral hepatitis C does not always require treatment. This is due to the fact that in some patients, thanks to the immune system, the infectious process stops and in some patients with a chronic variant of the disease, liver damage does not occur.

Access to treatment for hepatitis C virus is improving but remains limited. According to WHO statistics, in 2015 in the world of 71 million people with viral hepatitis C, only one in five (14 million) knew about their diagnosis. In the same year, only 7.4% of diagnosed people (1.1 million) started therapy.

The goal of therapy is destruction(eradication) of the pathogen to prevent the development of:

• cirrhosis of the liver;
• decompensation of formed cirrhosis of the liver;
• hepatocellular carcinoma (HCC);
• severe extrahepatic manifestations;
• death of the patient.

The criterion for the effectiveness of the treatment is the achievement of a certain level of virus RNA (<15 МЕ/мл), определяемой методом ПЦР (то есть достижение устойчивого вирусологического ответа - УВО) через 12 недель (УВО 12) и 24 недели (УВО 24) после завершения терапии. Долгосрочные наблюдения демонстрируют: достижение УВО приводит к полному излечению от заболевания более чем у 99% пациентов.

Eradication of the pathogen in patients with severe fibrosis or cirrhosis of the liver reduces the risk of decompensation of the condition and the development of HCC (but does not eliminate it completely). In patients with decompensated cirrhosis, eradication of the pathogen reduces the need for liver transplantation. After SVR is achieved, patients with cirrhosis or severe liver fibrosis should be registered with the dispensary.

Remember, you should not start self-treatment, moreover, you should not resort to non-traditional methods of therapy. Consultation with an infectious disease specialist is required.

New Therapy Opportunities

Standards of care for patients with HCV are changing rapidly. Daclatasvir, Sofosbuvir and the combination drug Sofosbuvir/Ledipasvir are included in international regimens that achieve a cure rate of 95%.

These drugs are called direct-acting antiviral drugs (DAAs). These drugs got their name because they directly act on the process of replication (multiplication) of the virus, unlike other drugs. These drugs are safer, better tolerated by patients, and much more effective than older therapies. More patients with HCV can be cured with DAA, and the course of therapy can be shortened (usually 12 weeks - about 3 months). The cost of producing these medicines is low, but they remain very expensive in many low- and middle-income countries. In some (mostly low-income) countries, the prices of these medicines have now been significantly reduced due to the introduction of generics (analogues of these medicines).

According to WHO statistics, in 2015 approximately 50% of people who started treatment received DAA. Over the years, the total number of patients worldwide who received treatment reached 5.4 million in the same year. Most of the patients who received treatment before 2015 were prescribed the “old” types of therapy (mainly drugs based on interferon).

The optimal duration of therapy should be based on the determination of the virus strain. The duration of therapy for the disease is determined by the attending physician, in accordance with international recommendations for the treatment of this disease.

Today, the following drugs are used for the treatment of HCV with the best results, presented in the table:

The list of these drugs was selected for the construction of modern treatment regimens in the CIS countries. The selection was based on information obtained from clinical studies and the use of these drugs for several years in Europe and North America.

If it is necessary to use Ribavirin, doctors are advised to conduct a preliminary careful monitoring of side effects. Please note that patients with blood disorders (hemoglobinopathies) may require a blood transfusion .

There are no absolute contraindications to treatment in the case of DAA-based regimens. Treatment is not recommended for patients with limited life expectancy due to concomitant diseases not associated with liver pathology. Possible therapeutic combinations of drugs for different HCV genotypes occurring in the territory of the post-Soviet space are presented in the table:

Recommendations for the treatment of people with chronic HCV without cirrhosis with/without HIV, including patients who have not previously received treatment or who have failed treatment without the use of DAAs are presented in the table: