Volume 03 Issue 02-2023
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International Journal of Medical Sciences And Clinical Research
(ISSN
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ABSTRACT
This scientific article discusses the causes of viral hepatitis, classification of hepatitis, symptoms, diagnosis of the
disease, treatment and prevention of viral hepatitis.
Research Article
MODERN METHODS OF TREATMENT OF VIRAL HEPATITIS
Submission Date:
February 18, 2023,
Accepted Date:
February 23, 2023,
Published Date:
February 28, 2023
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume03Issue02-14
Jamolbek A. Djuraev
Tashkent Medical Academy, Uzbekistan
Shokhimardon Kh. Khodjanov
Tashkent Medical Academy, Uzbekistan
Azizkhon Z. Shaumarov
Tashkent Medical Academy, Uzbekistan
Ulugbek P. Abdullaev
Tashkent Medical Academy, Uzbekistan
Abdurasul J. Botirov
Tashkent Medical Academy, Uzbekistan
Safura M. Mingboboeva
Kimyo International University In Tashkent, Uzbekistan
Solikha O. Dadakhanov
Kimyo International University In Tashkent, Uzbekistan
Lola T. Kuzieva
Kimyo International University In Tashkent, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 02-2023
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International Journal of Medical Sciences And Clinical Research
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KEYWORDS
Chronic viral hepatitis, cytolysis syndrome, alpha-interferon syndrome.
INTRODUCTION
Viral hepatitis B (HBV) is a viral anthroponotic
infectious disease with a blood-borne transmission
mechanism. The disease is characterized by cyclic
hepatitis, accompanied in some cases by jaundice and
possible chronicity.
Viral hepatitis causes more than one million deaths per
year. The European Association for the Study of the
Liver (EASL) is calling on various UN agencies to take
action to combat viral hepatitis, a potentially fatal
infection that infects 500 million people worldwide.
Even more worrisome is the fact that most people do
not know they are infected until the first signs of
infection appear, which could be liver cancer or liver
failure. The response to the appearance of virus
antigens in the div is the development of specific
total antibodies to HCV. The dynamics of the
appearance of antibodies to HCV in the blood of
infected individuals is variable, the average interval
from the onset of the disease to the appearance of
antibodies is about 15 weeks. (4-32 weeks), antibodies
against HCV in patients with chronic hepatitis are
detected for a long time, more than 7 years.
Morphology and physico-chemical properties. The
causative agent of HS is a small (30-38 nm in diameter)
RNA-containing, enveloped virus. The floating density
of HCV virions in the CsCl density gradient is 1.24 g/cm3,
in the sucrose gradient it is 1.08-1.11 g/cm3; the
sedimentation coefficient is 200 S. A lighter fraction is
also found, equal to 1.04
–
1.06 g/cm3, which is probably
due to the association of HCV with serum beta-
lipoprotein. The heavier fraction (1.17 g/cm3) in the
sucrose density gradient is most likely associated with
non-infectious immune complexes of the virus and
antibodies. The HCV nucleocapsid has a buoyant
density in the sucrose gradient of 1.25 g/cm3 [20, 23].
for 2 min in an aqueous solution. In addition, the so-
called “local” homologies (no more than 16 nt) with
classical swine fever and bovine diarrhea viruses
(Flaviviridae, Pestivirus) have been registered [31]. The
homology of HCV RNA with the genomes of plant
viruses suggested that in evolutionary terms, HCV
occupies an intermediate position between animal and
plant viruses. It was shown that HCV RNA contains a
highly conserved 5'-untranslated region up to 340 bp,
translation of the HCV genome. This RNA element
binds the 40S ribosomal subunit in the absence of
other translation initiation factors. The untranslated
region at the 3' end is terminated by polyuridine
ribonucleotides. They are followed by another highly
conserved 98
–
100 bp sequence called the X-tail, which
plays an important role in viral replication. The open
reading frame encodes a polyprotein consisting of
3,010
–
3,033 aa. When this polyprotein is translated, at
least 10 mature proteins are formed in the endoplasmic
reticulum of an infected cell.
The function of the NS4b protein is unclear, and the
NS5a protein modulates the effect of IFN on the virus.
In the NS5a protein, a region has been identified that
determines sensitivity to IFN. Mutations in this region
significantly reduce the effectiveness of IFN treatment.
It has also been shown that the NS5 protein is a potent
inhibitor of IFN-induced protein kinase PKR, which
Volume 03 Issue 02-2023
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International Journal of Medical Sciences And Clinical Research
(ISSN
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VOLUME
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(2023:
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Publisher:
Oscar Publishing Services
Servi
belongs to antiviral factors. The NS5a protein has RNA-
dependent RNA polymerase activity and plays an
essential role in RNA synthesis and replication. The
mechanism of initiation of RNA synthesis by viral RNA-
dependent RNA polymerase has not been completely
studied. persisting in the patient's div, the main
feature was revealed - the high heterogeneity of
certain parts of the genome [7, 10, 23]. Two
hypervariable regions of HCV RNA are distinguished. ,
is located at the 5'-end of the E2 gene. The second
hypervariable region (HVR2) with a length of 21 n.o. The
adjacency of the hypervariable regions of the HCV
genome provided the emergence of various HCV
genovariants. Analysis of the RNA of numerous HCV
variants circulating in different regions of the world
revealed the existence of major groups of the virus,
designated by types or genotypes (with less than 72%
nucleotide sequence homology between them) imum,
six major HCV genotypes.
A comparative analysis of the homology of HCV RNA of
different genotypes made it possible to establish the
presence of more than 100 subtypes (the level of
homology between different subtypes within the
genotype is 72
–
86%). In addition, the presence of
differences in sequences of 1
–
14% determines the
existence of multiple variants of the virus or its quasi-
species that appear as a result of long-term persistence
of the virus in the human div. An HCV-infected
patient may simultaneously harbor many millions of
HCV quasi-species. Phylogenetic analysis of HCV RNA
suggested that the division of HCV into genotypes
could occur from 500 to 2000 years ago, and the
division of genotype 1 into subtypes 1a and 1b more
than 300 years ago [2]. The high variability of HCV RNA
is associated with the appearance of point mutations,
insertions, and deletions that occur during virus
replication. Another mechanism that ensures the
variability of the virus genome is recombination, which
is characteristic of many RNA viruses: influenza virus,
HIV, poliovirus, and dengue virus. The study of
recombination between different HCV genotypes is at
the initial stage [7]. HCV circulation has been found
everywhere. According to WHO, the countries with the
highest percentage of chronically infected patients are
Egypt (2%), Pakistan (4.8%) and China (3.2%). The main
mode of transmission of the virus in these countries is
through the use of unprotected parenteral injection
methods and contaminated equipment. They
dominate Europe, North America, Asia and Oceania. In
European countries, subtype 1b is 50-91% (Germany -
59%, Belgium - 65%, Hungary - 84%, Italy (Sicily) - 91%),
and subtype 1a - no more than 40% (Germany - 32%,
Denmark - 40%, France - 35%). In the USA, subtype 1a
prevails, which even received the designation
"American genotype". The incidence of subtypes 1a
and 1b in the United States averages 37% and 30%,
respectively.
All other genotyped HCV variants are represented in no
more than 10%. In Japan, Taiwan, China (especially in
the southern provinces), Singapore, Indonesia, South
Korea, subtype 1b, the "Japanese genotype" is most
often detected (with the exception of the Philippines,
where the frequency of subtype 1b reaches 54.5%).
Subtypes 2a and 2b have a more limited distribution in
the world than subtypes 1a and 1b and a smaller
proportion among the genotypes represented in a
given area. The most common genotype 2 is
represented in Asian countries. Genotype 3 is most
common in Thailand (up to 50%), northern Europe (up
to 25% in the UK) and Australia. In the countries of
Central Asia, northern and central Africa, genotype 4 is
widely represented. Thus, among donors of HCV
carriers in Egypt, genotype 4 occurs in 30
–
40% of cases
of HCV detection. Genotype 5 is often detected among
patients with chronic hepatitis in South Africa, and
genotype 6 was identified in the countries of Southeast
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Asia, and CHC - 70. It should be noted that in 71
deceased, the etiology of chronic viral hepatitis was
not deciphered [6].
According to D.K. Lvova et al., subtype 1b dominates in
Russia [7, 8, 10, 12]. The share of subtype 1b is 64.7% in
various regions of Northern Eurasia, 80
–
83% in the Far
East, and 50
–
56% in the Central Black Earth and Volga-
Vyatka regions of Russia. Subtype 1a was most often
found in the Central, Northwestern, Volga-Vyatka
regions - 11.2
–
21.9%, while in the territory of Eastern
Siberia, the Central Black Earth region and the Urals it
can be detected extremely rarely (up to 5%). Subtypes
2a and 2b among people with HCV in Russia are also
classified as rarely detected (2a and 2b - 4.7
–
0.5%).
Recently, the proportion of subtype 3a in the
circulation of HCV in some regions of the Russian
Federation has increased significantly and reaches 40%
(long-term data from the D.I. Ivanovsky Research
Institute of Virology in Moscow and the Moscow
Region). HCV replication. Information on HCV
replication is still extremely limited and in most cases
contradictory. This situation can be explained by the
absence, until recently, of an available experimental
model of HCV. However, studies conducted in Russia
[3, 4, 5, 6] and in other countries [9] have made it
possible to develop experimental models of HCV in
vitro and in vivo. Reproduction of HCV in primary
cultures of brain cells of newborn white mice led to the
selection of infectious cytopathogenic variants of HCV,
characterized by a wide range of cell cultures sensitive
to virus replication. This allowed the isolation of high-
yielding HCV variants. Another model of HCV infection
in vivo, created in Canada, is based on the implantation
of the human hepatoma cell line Huh-7 in the liver of
nude mice. After infection of Huh-7 cells with HCV, it
was possible to find HCV RNA sequences in liver cells
and blood sera of mice. Features of the clinical course
of HS. The course of the disease varies from mild,
lasting for several weeks, to severe chronic infection,
lasting throughout life, leading to cirrhosis and liver
cancer [6, 9, 13]. The incubation period for HCV is 2
weeks. up to 6 months. After the initial infection, about
80% of people are asymptomatic. The acute phase of
HS is traditionally limited to 6 months. It can proceed
both imperceptibly for a person (doctors call this stage
subclinical or inapparent), and in the form of obvious
external manifestations. In acute infections, patients
have fever, weakness, loss of appetite, runny nose,
nausea, abdominal pain, dark urine, gray face, joint
pain, jaundice (yellowness of the skin and sclera of the
eyes). Approximately 75-80% of newly infected people
develop a chronic infection, and 60-70% of chronically
infected people develop chronic hepatitis, which in 5-
20% ends in cirrhosis of the liver, and 1-5% of chronically
infected people with HCV die from cirrhosis or cancer
liver. It is known that HCV is transmitted parenterally
and, first of all, by syringe in risk groups (drug addicts,
patients with hemophilia, patients in hemodialysis
units and other categories of persons in contact with
human blood or its products). According to WHO, the
most common way is the transmission of HCV by
infection with infected blood [11].
Risk factors for intrauterine transmission of HCV were
the presence of infection caused by HCV in both
parents and the use of psychotropic drugs by the
mother. Diagnosis of HS. Acute HCV infection is often
not diagnosed because most infected people show no
symptoms of the infection. Conventional antidiv
detection methods cannot differentiate between
acute and chronic infection. The presence of
antibodies against HCV indicates that a person is either
infected with the virus or has been previously infected.
Recombinant immunoblot assay (RIBA) and HCV RNA
testing are used to confirm the diagnosis. Diagnosis of
chronic infection is based on the detection of
antibodies to HCV in the serum of people for more than
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6 months. As with acute infection, the diagnosis of
chronic infection is confirmed by additional tests.
Special tests are often used to detect cirrhosis and liver
cancer. Early diagnosis can prevent health problems
that may result from infection and prevent
transmission among family members and other close
contacts. Some countries recommend screening of
populations at risk of HCV infection, including: people
who have received blood or blood product
transfusions who have had organ transplants prior to
screening; current or former drug addicts (including
those who took drugs once, many years ago) persons
on long-term hemodialysis; employees of medical
institutions of persons infected with HIV; people with
liver disease, or with poor results of tests reflecting
liver function; newborns from infected mothers.
Studies conducted in the field of HS diagnostics have
shown that HCV RNA is detected with the highest
frequency (up to 95%) by RT-PCR in human blood cells
(lymphocytes, mononuclear cells) than in human blood
serum (up to 76%). These data allow us to recommend
the use of 99At present, a method has also been
developed for the detection of antigenically active HCV
proteins in mononuclear cells of the peripheral blood
of patients with HS using monoclonal antibodies. The
non-mutant HH genotype of the hemochromatosis
gene (+63 H/D) was significantly more frequently
detected in the group of patients with mild CHC and in
the group of individuals characterized by a stable viral
response to therapy. In the Russian population, such
an association of IL-6 and HFE gene polymorphisms
with the achievement of a stable viral response in the
treatment of patients has been shown for the first
time.
Based on the data obtained, it can be assumed that the
likelihood of achieving a sustained viral response is
minimal in patients infected with the subtype 1b virus
and having allelic variants of the TT IL-6 gene and the
DD variant of the HFE gene with the aim of creating
experimental models of infection caused by HCV in
vitro for screening antiviral compounds [4]. The data
obtained made it possible to stably determine HCV
RNA persisting in cell cultures. Data on a wide range of
cell cultures sensitive to replication of isolated HCV
strains, as well as the collected collection of
cytopathogenic HCV strains, make it possible to use
them for screening antiviral drugs, since the problem
of treating HCV remains highly relevant. . As a result of
preclinical studies on the antiviral activity of the
compounds on the in vitro model of HCV infection, data
were obtained indicating the prospects for further
study of the antiviral activity of many drugs, including
birch bark extract - betulin and its derivatives, as well
as extracts of birch fungus (chaga) Inonotus obliquus -
Stimforte® [5,6]. Data were obtained on the high
antiviral effect of these drugs against HCV infection in
cell cultures. On May 13, 2011, the US Food and Drug
Administration (USFDA) approved the use of a new
protease inhibitor boceprevir (INN - boceprevir). The
drug was developed by Schering-Plough Corp., and
further, after the merger in 2009, research was
continued by Merck & Co., Inc. [35]. On May 23, 2011,
the USFDA approved the use of a new HCV protease
inhibitor (INH, telaprevir). The drug was developed by
Janssen in collaboration with Vertex and Mitsubishi
Tanabe Pharma [4]. According to clinical studies, new
HCV protease inhibitors are promising drugs. During
phase III clinical trials, patients in the study group
received telaprevir and peginterferon alfa2b/ribavirin
for 12 weeks, then telaprevir was canceled and therapy
continued with peginterferon alfa-2b/ribavirin, in some
patients for another 12 weeks, and in another part for
during 36 weeks. (12 + 36 = 48 weeks - standard
duration of HCV therapy with peginterferon alfa-2b and
ribavirin). In the telaprevir group, cure occurred in 60%
within 24 weeks, i.e. twice as fast as conventional
therapy.
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Summary results of the efficacy of telaprevir obtained
in phase III clinical trials: (sustained virological
response, standard therapy (peginterferon alfa-2b /
ribavirin) vs therapy in combination with telaprevir): in
individuals receiving antiviral therapy for the first time
: 46% vs 79% in previously treated patients: o in the
group with relapse 22% vs 86%; o in the group of partial
virologic response 15% vs 59%; o in the group that did
not respond to previous treatment 5% vs 32% .It has
been shown that telaprevir should not be combined
with a number of other drugs, in order to avoid an
increase in the risk of side effects and / or a drop in drug
concentration and the risk of virological failure:
atorvastatin,
lovastatin,
simvastatin,
pimozide,
rifampicin, alfusion, sildenafil, tadalafil, triazolam, St.
John's wort and ergot preparations. The drugs have
been shown to increase the risk of developing a
number of side effects, such as skin lesions, rashes,
neutropenia, anemia, disorders of the gastrointestinal
tract. The prospect of developing a vaccine against HS.
To date, there is no vaccine against HS [8]. At the same
time, according to WHO recommendations, you can
reduce the risk of infection if: try to avoid the use of
unnecessary and unsafe injections; try to avoid the use
of blood products suspected of HCV infection for
medicinal purposes; collect and dispose of unsafe
stabbing waste; prevent illegal drug use and the
sharing of injecting equipment; avoid unprotected
intercourse with infected HCV; prevent sharing of
sharp objects that may be contaminated with infected
blood; tattoos, piercings and acupuncture, etc. Since
the discovery of HCV, intensive research has begun to
develop a vaccine against HS. Due to the fact that
infectious strains of HCV have not been isolated from
materials from patients, research is being carried out
towards the development of genetically engineered,
recombinant, subunit, peptide and DNA vaccines.
Research conducted at the Research Institute of
Virology
CONCLUSION
The problem of viral hepatitis B remains relevant due
to the widespread prevalence of infection, the ease of
implementation of transmission routes, and the
possibility of developing chronic forms. The problem of
viral hepatitis B is of particular relevance for primary
health care physicians. Knowledge of the etiology,
pathogenesis and features of the specific diagnosis of
viral hepatitis B will allow family doctors to identify not
only clinically pronounced, but also latent forms.
Diagnosis of these forms of the disease will help reduce
the prevalence of HBV infection
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