Etiology and nataphysiology
The hepatitis C virus (hereinafter referred to as HCV) refers to the RNA-containing viruses of the family Flaviviridae. By itself, it does not have a cytopathic effect. The destruction of hepatocytes is primarily due to the hypertrophic response of the immune system.
Many different genotypes of HCV have been described, in our country genotype 1b is the most common. Genotypes 3, 1a and 2 are much less common, the rest are only casually detected:
Clinical picture
Chronic hepatitis C is noted in 80% of cases of HCV infection. In most cases, the symptoms are either absent or characterized by nonspecificity (fatigue, fatigue, poor health, subfebrile fever).Brighter develops symptoms in decompensated liver cirrhosis and portal hypertension (edema, ascites, esophageal varices and the associated bleeding, thrombocytopenia, and so on).
In the literature mentioned large number of chronic hepatitis C. The pathogenesis of most of them is extrahepatic immune-mediated complications (cryoglobulinaemia, membranoproliferative glomerulonephritis, lichen planus, Sjögren's syndrome, and others.). HCV significantly increases the risk of a number of extrahepatic malignancies, primarily non-Hodgkin's lymphomas.
A variety of skin complications of chronic hepatitis C:
Diagnostics
- The primary screening laboratory examination is serology (definition antibodies to HCV). The test has high specificity, but it does not allow to distinguish acute process from chronic. In addition, there is an increased risk of false-negative results in immunocompromised patients.
- When detecting antibodies, it is necessary to conduct a verification test - qualitative determination of HCV RNA (viremia).
- With a positive result, it is necessary to determine the viral load (quantitative test) and genotyping, since the genotype of the virus has a significant effect on the prognosis of the disease and the probability of successful treatment.
- The analysis of polymorphisms associated with the IL28B gene has been very often performed in the past, as it allowed one to assess the likelihood of a stable virologic response to treatment with pegylated interferon and ribavirin. Today, this test loses its relevance, since the classical scheme is replaced by drugs of direct action (see below).
- Other necessary laboratory tests: general and biochemical blood tests, rheumatoid factor, cryoglobulins, antinuclear antibodies, HBs-antigen / anti-HBs, antibodies to HIV.
- Necessary instrumental examinations: ultrasound of the abdominal cavity, elastometry of the liver (noninvasive method for determining the severity of fibrosis), esophagogastroduodenoscopy (to assess the state of the esophagus). If an ultrasound reveals focal formation, it is necessary to conduct a computed tomography with intravenous contrast.
Treatment
In recent years, antiviral therapy for hepatitis C has gone far ahead: the introduction of direct-acting drugs has made it possible to achieve a stable virologic response in> 90% of cases in a short time (8-12 weeks) and without significant side effects.
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The key groups of direct-acting antivirals are:
Often, these drugs are available in the form of combinations, for example:
sophosbuvier + ladypasvir, grazoprevir + elbasvir and others. Some schemes involve the combination of direct action drugs with ribavirin and / or pegylated interferon. The effectiveness of a particular combination depends on the genotype of the virus, the presence of liver cirrhosis, compensation of the pathological process and a number of other factors.
In the conditions of our country, the most urgent issue is the treatment of HCV genotype 1. In this regard, attention is drawn to the drug Viqueira Pak, which is a combination of several antiviral drugs (dasabuwir, ombitasvir, paritrapevir).In order to slow the CYP3A-mediated degradation of pariteprevir, a small dose of ritonavir that is an inhibitor of CYP3A is specifically added to this combination.
During the large clinical trials of PEARL-II and PEARL-III, the drug demonstrated the highest efficacy against HCV genotype 1b (the most common in Russia) - the frequency of achieving a stable virologic response was 100% (!). The established efficacy of the drug against genotype 1a was only slightly less: 96% in patients without cirrhosis and 95% in patients with compensated cirrhosis.