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Editorial Board |
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Review |
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BIOMARKERS FOR SYSTEMIC SCLEROSIS - TOOLS FOR DIAGNOSIS
AND TREATMENT Introduction. Systemic sclerosis (SSc) is
an autoimmune disease characterized by skin and internal organ fibrosis
with prior vascular and immune dysfunction. Depending on the cutaneous
fibrosis degree, SSc is
divided into two main subtypes: limited skin SSc (LT-SSc) and
diffuse skin SSc (DF-SSc).
This classification is characterized by
association with certain autoantibodies that specifically define these
clinical phenotypes. Despite ongoing research, so far only a few
biomarkers of SSc have
been fully validated, approved and implemented into practice. Material and methods. This paper presents a literature
review of promising SSc prognostic
biomarkers, biomarkers of disease activity, skin fibrosis and internal
organ lesion with the aim of providing comprehensive information on the
applicability of biomarkers for research and clinical use. A literature
search was conducted in the PubMed, MedLine,
Scopus and Embase databases from
2000–2018. Keywords used for search: systemic sclerosis, anti-nuclear
autoantibodies, non-specific autoantibodies, biomarkers. Results
and discussion. The presence of autoantibodies is the central
determining aspect of autoimmune diseases. Autoantibodies are found in the initial diagnosis of more than 95% of SSc patients and associated with different
disease subtypes and the clinical course severity. Antitopoisomerase I (ATA), or anti-Scl-70
antibodies, and anticentromere (ACA)
antibodies are the most widely used SSC diagnostic biomarkers. ATA is observed mainly in patients with DF-SSc, associated with a worse prognosis,
increased mortality, the digital ulcer development, pulmonary fibrosis
and heart damage. ACA is detected in 90% of
patients with LT-SSc. In patients with
Raynaud's phenomenon, ACA predicts the occurrence of LT-SSc. ACA positivity correlates with a more
favorable prognosis and lower mortality compared with positivity for
other autoantibodies associated with SSc.
Antibodies against RNA polymerase III (anti-RNP III) are highly
specific for patients with SSc (98–100%).
Anti-RNP III is associated with DF-SSc,
debut in old age, a renal crisis and a
high risk of a malignant tumor developing. Anti-Th/To
are clinically associated with LT-SSc and
are the marker for the worst survival. Anti-U3RNP is often associated
with DF-SSc, the visceral organ
involvement, especially kidneys and heart. The presence of UI RNP
antibodies is associated not only with SSc, but also with systemic lupus erythematosus
(SLE), rheumatoid arthritis (RA), myositis, many patients have criteria
for mixed connective tissue disease. More recently, autoantibodies to
type 1 angiotensin II receptor (AT1R) and type A
endothelin-1 receptor (ETAR) have been found to be elevated in the
serum of most patients with SSc and are
associated with vascular and fibrous complications. Relatively rare and
less specific antibodies are anti-U11/U12 RNP, PM/Scl
antibodies, antibodies against estrogen receptors α, anti-endothelial cell antibodies, anti-fibroblast
antibodies, anti-platelet-derived growth factor receptor antibodies. It has been shown that the
elevated expression of pro-fibrotic miRNAs and reduced expression of antifibrotic miRNAs are important factors in the
developments of fibrosis in SSc. Unlike other autoimmune diseases, such as SLE or RA, for
many patients with SSc it is difficult to
assess the presence of current inflammation,
it is not easy to determine the blood vessel and tissue fibrosis,
especially at an early stage of the disease. Biochemical markers
candidates for assessing the activity and severity of the disease in SSc were obtained
based on the presence of an association with target organ damage. Serum
von Willebrand factor, glycoprotein Krebs
von den Lungen 6, procollagen-III aminoterminal-propeptide, tissue inhibitor of matrix metalloproteinase-1, IL-6,
growth factor differentiation 15, the serum level of cartilage oligomeric matrix protein, angiopoietin/Tie2 and hyaluronic acid showed a significant correlation
with both the activity and the severity of the disease. Conclusion.
Thus, serum autoantibodies are considered
important biomarkers for early and accurate diagnosis of SSc and are associated with distinctive clinical
subgroups and various prognostic signs of this disease. It has been demonstrated that some autoantibodies
directed against autoantigen specific targets induce inflammation,
activate fibroblasts, promote the synthesis and deposition of collagen,
and activate endothelial cells, participating in the pathogenesis of SSc. Understanding the pathogenic role of
autoantibodies in SSc can help identify
new therapeutic targets for this complex disease.
Keywords: systemic sclerosis, biomarkers, antinuclear antibodies,
non-specific autoantibodies, fibrosis, pulmonary hypertension,
prognosis. |
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Experimental works |
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THE EXPLANATON OF THE SELECTION OF BASIC DETERGENTS AND
SECONDARY DETERGENTS FOR THE DEVELOPMENT OF FOAM MEANS WITH MINIMUM
IRRITANT ACTION: A REVIEW Petrovska, L.S. , Baranova I. І., Bezpala, Yu.O., Introduction. Modern detergents are different from those products
which satisfied the needs of consumers of the last century (for
example, they had a stable foam, a bright color due to synthetic dyes,
sometimes rich liquorice smells, etc.). At the present time, the consumer has became more selective when choosing foaming
agents of different orientation. Analyzing the entire information
space, we noticed that manufacturers develop foam materials on the basis of classical technology, that is,
they combine anionic, amphoteric, nonionic detergents, and also add
auxiliary substances such as viscosity regulators, corients,
pH values, and others. We also noted that the modern manufacturer began
to prefer detergents or even their combinations, which in turn would
have less irritant activity on the skin and mucous membranes. Materials
and methods. As materials we used
informational and literary sources that highlighted the main
characteristics of modern basic and additional detergents. Also, we used conventional methods of research,
namely historical, logical, comparative and structural. Results.
Usually, in formulations of foaming agents, which are
represented in the Ukrainian market, mostly detergents of
anionic nature, such as sodium laureth
sulfate, sodium lauryl sulfate, are presented. The washing properties
in them provide a surface-active anion: a negatively charged particle
of a molecule. It is the anions that give a
massive foam. But since the surface of our
skin has a polymozaic charge, the efficacy
of cleaning with such a detergent is not the best one. Therefore,
lately, modern manufacturers combine either
nonionic and amphoteric detergents or combine them with mild
anionic substances such as sodium mentresulfate,
sodium laurylsarkosinate, magnesium laureth sulfate, and etc. After analyzing
literary sources and taking into account the manufacturer's advice, we
identified the main "soft" surfactants that are currently used:
Magnesium Laureth Sulfate, Sodium Lauroyl Sarcosinate, Sodium Myethyrsulphate,
Disodium Lauryl Sulfosuccinate, Disodium Laureth
Sulfosuccinate, Disodium Ricinoleamido MEA-Sulfosuccinate, Sodium
Laureth-11 Carboxylate, Laureth-7 Citrate. As additional
detergents in foaming agents, various amphoteric, nonionic, some
anionic and crypt-anionic detergents are commonly used. Conclusions. The analysis of the nomenclature and
characteristics of modern detergents of different nature of origin,
namely anionic, amphoteric and nonionogenic, is carried out. It has been established that a
wide range of detergents is currently used, which can be used in
various applications, for example, from children's foam to shower gels.
It is noted that due to the use of
detergents with minimal irritant action, it is possible to create a
group of sputum funds not only with satisfactory consumer and
physicochemical indicators, but also with a limited interval of pH. Key words: foaming agent, detergents, additional detergents,
anionic, amphoteric, nonionic |
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17-20 |
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DEVELOPMENT OF THE COMPOSITION AND TECHNOLOGY OF
EXTEMPORANEOUS SUPPOSITORIES WITH СLINDAMYCIN AND SEA BUCKTHORN OIL Chushenko V.M., Yarnykh T.G., Osolodchenko T.P., Yuryeva
G.B., Herasymova I.V. Introduction. Antibacterial therapy certainly plays an important role
in the treatment of these pathologies, although in most cases it causes
allergic states, antibiotic resistance of various types of
microorganism strains, and also a disfunction of normal vaginal biocoenosis.
Anti-protozoal, antibacterial and antifungal agents are preferred,
namely, ternidazole, metronidazole,
fluconazole, clindamycin, miconazole, clotrimazole,
nystatin, isoconazole etc. among the
synthetic drugs used in gynecological
practice. Prospective plant medicines for solving this problem are essential
oils (tea tree, sea buckthorn, wormwood, chamomile), which provide
inhibition of the development of pathogenic anaerobes. The aim of the
work was to substantiate the composition and development of technology
of combined vaginal suppositories (pessaries) with clindamycin
phosphate and sea buckthorn oil for the treatment of
infectious-inflammatory gynecological
diseases. Materials and
methods. Model samples of suppositories were prepared with 0.100 g
of clindamycin phosphate and 0.500 g of sea buckthorn oil. Disperse system of suppositories with clindamycin and sea
buckthorn oil is an emulsion of 1st type,
therefore it is possible to use as emulsifiers the following
substances: polysorbate-80, emulsion wax or alkaline soaps. Model samples of suppositories with clindamycin phosphate
and sea buckthorn oil were checked by pharmaco-technological parameters (description,
homogeneity, disintegration time, pH). The study of antibacterial properties of suppository
model samples with clindamycin and sea buckthorn oil was carried out. Results and discussion. Samples of suppositories with polysorbate-80 become
homogeneous and meet the requirements of the SPhU
2.0. The results of the conducted researches of pharmaco-technological parameters shown that
model samples of suppositories with clindamycin phosphate and sea
buckthorn oil meet the requirements of the SPhU
2.0 for the following parameters: description, homogeneity,
disintegration time, pH. Conclusions. The composition and technology of suppositories with
clindamycin phosphate and sea buckthorn oil for pharmacy preparation
was developed. A technological instruction for the pharmacy preparation
of suppositories has been developed and tested in the conditions of
pharmacy. Keywords: suppositories, technology, suppository base, clindamycin
phosphate, sea buckthorn oil. |
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21-24 |
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DETERMINATION OF MICROBIOLOGICAL PURITY OF TABLETS FOR
THETREATMENT AND PREVENTION OF TYPE II DIABETES MELLITUS Kovalevska IV, Ruban O.A., T. P. Osolodchenko Introduction. Diabetes mellitus refers to a group of metabolic
diseases characterized by hyperglycaemia,
which occurs as a result of a defect in
secretion or action of insulin. Chronic hyperglycaemia
in diabetes mellitus (DM) leads to a damage, dysfunction and
insufficiency of various organs, especially the eyes, kidneys, nerves,
heart and blood vessels. Consistent hyperglycaemia
activates the formation of free radicals, reduces the activity of
antioxidant protection agents: superoxide dismutase, catalase,
glutathione peroxidase, vitamins C and E. Therefore, special attention
deserve anti-diabetic drugs which, along
with the hypoglycaemic effect, have
antioxidant properties, the ability to maintain or improve the
secretory function of β-cells. The optimal compositions have been
established and the technologies of medicinal products under the
conventional names "Glycverin" with Voglibose and quercetin and "Thioquerin " on
the basis of solid dispersion of thioctic
acid were developed by previous studies. As a
result of the study of specific pharmacological activity, it has
been experimentally proved that the above drugs have a pronounced hypoglycaemic effect and increase the
bioavailability of their components, which suggests its relevance in
the treatment of type II diabetes. In order to increase biological
availability, the method of solid dispersion has
been utilized, which has significant advantages, among which:
the use of drugs in solution or finely dispersed state provides a high
dissolution rate, reduced irritating action on the gastric mucosa, a
high therapeutic effect. However, during the technological process of
obtaining non-sterile dosage forms, the preparation may
be contaminated with microorganisms, which may reduce its
stability during storage, which negatively affects its safety profile.
Today, SPU clearly regulates the maximum level of contamination by
microorganisms for each dosage form. Material &
methods. The objects of the study were tablets under the
conventional names "Glycverin" and "Thioquerin". Studies on the microbiological
purity of the tablets were conducted in
accordance with the requirements of the SPU, 2nd ed., p.2.6.12 and
2.6.13, category 3A (5.1.4, N). For the study used: soybean casein
broth (HIMedia Laboratories Pvt.Ltd India » expiration date of the medium
until XI 2019, Manufactured in India). For Candida
albicans used Saburo-Dextrose
Agar (Indian Production, «HIMedia
Laboratories Pvt.Ltd India » expiration
date of the environment until XI 2019). The environments were prepared
according to the manufacturer's requirements (amount of powder per litre, pH, conditions of autoclaving, etc.).
Each series used in the experiment was tested
on growth quality in accordance with the reference documents. For tests
on microbiological purity the following
media were obtained on the basis of soy-casein agar: Chistovich's medium, blood agar. Results & discussion. Before conducting research on microbiological purity it was mandatory to test the compliance of
the growth qualities of the nutrient media used. For this purpose, the
nutrient media were inoculated with a small amount of an appropriate
test strain of the microorganism (10 - 10 2 colony forming
units per ml of medium - CFU / ml). The obtained data indicate that all microorganisms were
consistent with the taxonomic designation of the strain, the morphology
of the colonies when cultured on the media and cell morphology in
microscopy were typical. Nutrient broths (soy-casein and thioglycolic medium) met the requirements for
sterility - there was no growth of microorganisms, the environment was
transparent. When testing on microbiological purity, the direct
sowing method was used for liquid nutrient
media. After 14 days of incubation, at cultivation on a Saburo, soy-casein broth and thioglycolic medium the growth of fungi was
absent. In a deep sowing study, which was to add 0.1 g of preparation
to agar and surface sowing of 0.1 g to agar, the amount of viable cells
of microorganisms and fungi has been determined. The study of surface
and deep sowing of drugs on Saburo dishes
has shown no growth of fungi. The data obtained in Table 3 indicate that the number of
microorganisms does not exceed 10 3 CFU / ml, which meets
the requirements of the State Pharmacopoeia of Ukraine. Conclusion. The study of microbiological purity of tablets "Glycverin" and "Thioquerin"
has been conducted. The results
indicate absence of viable fungal cells. It has been established that
the amount of viable cells of microorganisms does not exceed 10 3 CFU /
ml in 1 g of the preparation, which meets the requirements of the SPU
for internal use preparations. Strains S. aureus, P. aeruginosa and
representatives of Enterobacteriaceae sp.
family have not been detected. Investigated
samples of drugs meet the requirements of the Pharmacopoeia of Ukraine
on the indicators of microbiological purity for oral preparations. The
obtained results allow asserting the safety and expediency of further
development of medicinal products for use in the treatment of type II
diabetes mellitus. Keywords: Diabetes mellitus, solid dispersion, microbiological purity, thioctic acid, quercetin |
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RESEARCH ON THE CHOICE OF RATIONAL CONCENTRATION OF THE
GEL FORMING AGENT IN THE COMPOSITION OF DENTAL GEL Ruban O. A., Maslii Yu. S. Taking into account the wide spreading and etiopathogenetic features of the course of
inflammatory diseases of periodontium and oral mucosa, it is rational
to use semisolid drugs of local action, namely, dental gels. The main
issue when developing this dosage form is the choice of the gel former
and its concentration. Based on previous studies as the gel basis for
the development of a new dental gel with «Phytodent»
tincture, choline salicylate 80%, and lidocaine hydrochloride the Carbomer Polacril®
40P, which is authorized for use in
dentistry and has the ability to form transparent viscous
aqueous-alcohol gels, has been chosen. It is known
that rheological characteristics of gels directly affect the processes
of release and absorption of active pharmaceutical ingredients from a
semisolid dosage form, as well as its consumer properties. The
important issue is the convenience and ease of application of a dental
gel to inflamed tissues of periodontium and mucous membranes. This
process is similar to that occurring during the shift of visco-plastic material in a rotary viscometer.
The aim of the work is to study the structural and mechanical
characteristics of the developed dental gel in order to select the
rational concentration of the carbomer Polacril® 40P. Materials and methods. The study objects are gel samples
with different concentrations of Carbomer Polacril® 40P – 1.0, 1.25, 1.5, 1.75 and 2.0 %.
Measurement of the rheological parameters of the model gel samples was carried out at a temperature (25 ± 0.1) оС on a rotary viscometer with coaxial cylinders
"Rheolab QC" ("Anton Paar")
before and after contact with a solution of artificial saliva. As
standards for comparison dental gels "Dentinox-gel N" (Germany) and gel "Metrogyl Denta®"
(India) were selected. Results and discussion. It has been found that all gel samples have a
non-Newtonian pseudoplastic flow type and
are thixotropic systems with pronounced limits of fluidity. The
rheological parameters of the dental gel samples increase as the
concentration of Carbomer Polacril® 40P increases. In the nature of rheograms and structural viscosity
the closest indicators to the drug "Dentinox-gel
N" have gels with carbomer concentration
of 1.25 % and 1.5 %, and to the drug "Metrogyl
Denta®" – 1.75 % and 2.0 %. Conclusions. Taking into account the results of
structural and mechanical studies of gels with and without an
artificial saliva solution, as well as in terms of profitability, the
optimal concentration of Carbomer Polacril® 40P in the composition of the
developed gel was chosen to be 1.5 %. Keywords: dental gels, gel former, rheological studies. |
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DEVELOPMENT OF THE POWDER COMPOSITION WITH THE SORBING,
ANALGESIC AND ANTIMICROBIAL ACTIVITY BASED ON NATURAL ZEOLITE Rybachuk V. D., Ruban O. A. Introduction. An active lifestyle, playing sports, participating in
hiking trips and various competitions, as well as performing certain
types of physical labor may be accompanied
by injury. Damage of the skin requires its immediate treatment. Powders
are an alternative to soft dosage forms, which are
usually used for this purpose. Powders are
used in acute inflammatory skin diseases, with a hygienic
purpose in increased sweating and sebum secretion, to protect the skin
from external irritations, as well as for better fixation of ointments
and pastes on the skin. Aim. To select the composition
of active substances and excipients for creating a powder with the sorbing, analgesic and antimicrobial activity
based on natural zeolite. Materials & methods. The
study objects were model powder compositions containing a filler
(natural zeolite), anesthetic (pyromecain),
antifriction substances (talc, magnesium oxide, silicon dioxide) and
antimicrobial substances (neomycin sulfate and polymyxin B sulfate).
The quality of the samples was assessed by
indicators of bulk and tapped densities, flowability,
the Hausner ratio (H) and the Carr index (C). The osmotic activity was assessed by dialysis through a semipermeable
membrane. For performing the tests the
methods of the State Pharmacopoeia of Ukraine (SPhU)
were used. Results & discussion. Powders with 5 % pyromecain showed the most optimal properties by
the time of the start and duration of anesthesia; however, a further
increase in its concentration did not give a significant effect. The
technological properties of powders depend on both the type and
concentration of antifriction substances. The addition of talc and
magnesium oxide increased the density of powders by 2-18 %, and silicon
dioxide reduced the density by 31-47 %. The
flowability (100 g/s) of samples with
talc was 48.4-69.4, with magnesium oxide – 65.7-72.2, and with silicon
dioxide – 19.8-40.6. The most significant improvement in flowability occurred after adding silicon
dioxide; therefore, this substance in the amount of
5 % was chosen for further research. The adsorption properties of the
powder were characterized as moderate. The
osmotic activity was 73 %. Conclusions. The studies on
selection of active substances and excipients for creating a powder
with the sorbing, analgesic and
antimicrobial action based on natural zeolite have
been conducted. The following composition of the medicinal
product has been proposed: natural zeolite (clinoptilolite) – up to 25.0 g, neomycin sulfate
– 5000 IU/g, polymyxin B sulfate – 10.000 IU/g, pyromecain
– 1.25 g (5 %) and silicon dioxide – 1.25 g (5 %). Keywords: natural zeolite; powder; excipients; pyromecain; osmotic activity |
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RESEARCHES ON PHARMACEUTICAL DEVELOPMENT OF SOLID GELATINE
CAPSULES WITH DRIED MULTIPLE COMPONENT EXTRACT OF ANTIPHLOGOGENIC,
DIURETIC AND CHOLERETIC ACTION Shmalko O. O., Vyshnevska L. I. Introduction. Pharmaceutical drug development is based on the selection
and study of the drug-comparison, safety and efficacy, taking into
account the route of administration, the dosage form, the
substantiation of the composition and concentration of the active
pharmaceutical ingredient (API) and the excipients, bioavailability,
strength and stability; identifying potential critical quality
indicators; the choice and proposals of optimal technological scheme
for obtaining this drug, the definition of critical operations and
parameters of the technological process; definition of strategy of
control, development of specifications and methods of control of raw
materials, intermediate, non-prepackaged
and finished products; the choice of packaging; validation or
verification of methods of quality control of a medicinal product;
carrying out studies on the stability of the medicinal product during
the predicted shelf life. One of the components of the delivery of the API to the
site of the pathology is the dosage form of the drug, which
significantly influences the preservation of its effectiveness,
determining the degree of absorption and concentration in biological
fluids. Recently, the attention of developers attracts a dosage form of
capsule, which among the dosage forms of industrial production occupies
the third place after tablets and solutions in ampoules. They have more
advantages (accuracy of dosing, high bioavailability, stability and
productivity of obtaining, corrective ability, minimization of
production errors, aesthetics, the ability to provide medicinal
products with planned properties: the ability to dissolve in certain
parts of the gastrointestinal tract, possess prolonged release of the
API), sparing technological mode, etc.). The aim of our work was to
develop the technology of medicinal product in the form of capsules
with an active pharmaceutical ingredient - a dry extract of urocholum, possessing anti-inflammatory,
diuretic and choleretic properties, as
well as to determine the critical parameters in their production. Material&methods.
Pharmaco-technological research
methods were applied. Results&discussion. The
technological process of production of capsules with a multi-component
dry extract consists of the following stages: sifting of raw materials,
preparation of mass for encapsulation (mixing of components, rubbing);
encapsulation; packing of capsules into blisters; packing blister
packs; packing bundles in boxes. On 3 experimental industrial series (0040319, 0050319, 0060319), it was validated by the technological
process of producing urocholum capsules
and proved its reproduction in industrial conditions. With the help of
the Ishikawa diagram, the most significant aspects that influence the
technological process and which need to be
controlled at the routine production of capsules of urocholum were identified. The design of a
technological regulation for the production of gelatinous capsules with
a multi-component dry extract possessing anti-inflammatory, bile and
diuretic properties was developed and tested in industrial conditions
of the LLC DKP "Pharmaceutical Factory", Zhytomyr. Conclusion.
1. Based on the complex of scientific and experimental
researches, the optimum technological mode of production of hard
gelatinous capsules with a multi-component dry extract with
anti-inflammatory, choleretic and diuretic
activity was established. 2. The critical stages of the process of gelatinous
capsules being developed and the parameters
of their control and the criteria of acceptability according to the
requirements of the SPHU were determined. 3. Technology has been tested
in the conditions of industrial production of LLC DKP "Pharmaceutical Factory", Zhytomyr, in accordance with the project of the technological
regulations for the production of gelatin capsules with a
multi-component dry extract. Keywords: pharmaceutical development, solid gelatine capsules,
multi-component extract. |
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MODERN PHARMACOTHERAPY OF CHRONIC HEPATITIS C DEPENDING
ON THE GENOTYPE OF THE HEPATITIS C VIRUS Kiryev I.V., Zhabotynska N.V. Hepatitis C is an infectious disease of the liver caused
by the hepatitis C virus (HCV), which affects the liver and causes
inflammation. This virus can cause both acute and chronic course of
hepatitis in (70-80% of patients), which can vary according to the
severity of the disease. The World Health Organization (WHO) estimates
that about 71 million people worldwide suffer from chronic hepatitis C.
According to estimates by national experts, Ukraine is among the
countries with an average prevalence of hepatitis C. Every year, about
6,000 people are diagnosed with hepatitis
C. There are 24,786 patients on the waiting list for treatment in
Ukraine. Injecting drug users (IDUs) are most at risk of contracting
HCV. The highest rate of HCV transmission is found
in men who have sex with men. HCV can also be
transmitted through tattoos, razors and acupuncture.
Transmission of HCV from mother to fetus can be observed in about 4-5% of cases.
Breastfeeding is safe. HCV is a spherical, enveloped, single-stranded
RNA virus belonging to the Flaviviridae
family. A genomic analysis of HCV led to the division of the hepatitis
C virus into six genotypes. Subtype analysis was also righteous, which
improved the genomic classification of HCV. HCV subtypes pose a serious
problem for immune-mediated control of HCV and can explain the diverse
clinical course of the disease and the difficulties in vaccine
development. The article analyses the recommendations of the American
Society of Infectious Diseases (IDSA) and the American Association for
the Study of Liver Diseases (AASLD), in collaboration with the US
International Antiviral Society (IAS-USA) on the pharmacotherapy of
chronic viral hepatitis C. The
pharmacotherapy of chronic HCV has two goals: 1. Achieving sustained
HCV eradication or sustained virological
response (SVR) – no serum HCV RNA 12 weeks after the completion of
antiviral treatment. 2. Prevent the progression of cirrhosis,
hepatocellular carcinoma, and decompensated liver disease requiring
liver transplantation. To date, pharmacotherapy of chronic viral
hepatitis C uses a combination of pegylated
interferon (PEG-IFN) with ribavirin and direct-acting antiviral drugs
(DAD). At the same time, very recently, priorities have
been removed from the AASLD/ISDA recommendations and today
treatment is strongly recommended for all patients with chronic viral
hepatitis C. The addition of the oral
nucleoside analogue of ribavirin to the PEG-IFN pharmacotherapy regimen
marked a new era in the treatment of chronic HCV. The use of such a
combination led to sustained eradication of HCV in 30-40% of cases.
Pharmacotherapy with PEG-IFN alpha-2a and ribavirin can
be individualized by genotype. Patients with HCV genotype 1
require treatment for 48 weeks and a standard dose of ribavirin.
Patients with a genotype of 2 or 3 HCV genotypes adequately receive a
low dose of ribavirin for 24 weeks. Relatively
recently, a number of DADs were developed for specific effects on
various replication sites of the hepatitis C virus. These include: protease inhibitors NS3 / 4A (boceprevir, voxilaprevir,
telaprevir, simeprevir,
grazoprevir, glecaprevir);
NS5B protease inhibitors (sofosbuvir, dasabuvir); protease inhibitors NS5A (ledipasvir, daclatasvir,
ombitasvir, elbasvir,
velpatasvir, pibrentasvir).
To date, according to the WHO recommendations, for the treatment of
chronic viral hepatitis C, depending on the HCV genotype, in patients
over 18 years old who have not received treatment, fixed combinations
of DAD are used at the daily dosage. DAD
for interrupting HCV replication in various places in different
combinations showed 90-95% registered SVR compared to 50-70% in
patients treated with PEG-IFN combined with ribavirin. However,
clinicians should be aware that amino acid substitutions in the viral
protein, associated with resistance to inhibitors and leading to drug
resistance, can worsen the response to
treatment of DAD, in particular, the base NS5A resistance in patients
with chronic viral hepatitis C. Keywords. Hepatitis C, chronic, treatment, protocols, genotypic
of virus dependence
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