CC BY
15UDC : 616.36-002-036-07-08
Melenko Svitlana Romanivna,
PhD. Associate Professor of the Department of Infectious Diseases and Epidemiology
Bukovinian State Medical University Kulyk Aleksandra Oleksandrivna,
Student
Bukovinian State Medical University
Korduban Kateryna Vitaliivna.
Student
Bukovinian State Medical University.
DOI: 10.24412/2520-6990-2023-9168-61-63 HEPATITIS C: STATE OF THE ART, PROGRESS AND PROBLEMS DIAGNOSTICS AND
TREATMENT.
Abstract
Hepatitis C virus (HCV) continues to pose a serious threat to public health, causing a significant burden both epidemiological and clinically. New HCV infections are still occurring, especially in some of the poorest regions of the world where HCV is endemic and the long-term consequences carry a growing economic and health burden. Transmission by known parenteral routes is frequent; other routes of spread are less common and may represent latent, percutaneous dissemination.[2] After infection, most people apparently remain carriers of the virus, with varying degrees of hepatocyte damage and fibrosis. Chronic hepatitis can lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely: from less than 2 years to cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. There is still no vaccine against HCV despite years of research and discovery, but the variability of the virus and its ability to adapt are major challenges in vaccine development. In this review we discuss modern concepts of epidemiology, clinic, diagnosis, therapy and prevention of hepatitis C.[1]
Keywords:Hepatitis C virus diagnostics; hepatitis C virus epidemiology; hepatitis C virus vaccine; direct-acting antivirals; predictors of response to hepatitis C virus therapy.
HCV EPIDEMIOLOGY. HCV has a single-stranded RNA and belongs to the family Flaviviridae. Its genome encodes the synthesis of structural (protein C, or soge protein), envelope (elelope; E1- and E2/NS1-glycoproteins) and non-structural (NS2, NS3, NS4, NS5) proteins. Today there are 11 genotypes of the virus, more than 100 subtypes and a large number of so-called quasi-species. The latter play a major role in the formation of treatment-resistant strains of the virus. Genotypes Ia, 1b, 2a, 26, 2c and 3a account for more than 90% of all virus isolates obtained in North and South America, Europe, Russia, China, Japan, Australia and New Zealand. Genotypes 4, 5a and 6, respectively, are found in Central and Southern Africa, Southeast Asia. In Ukraine and other CIS countries, genotypes 16 (about 70%) and 3a predominate.[6]
HCV PREVENTION. Primary prevention of new infections and treatment of existing infections (secondary prevention) are fundamental approaches to controlling the HCV epidemic. As already noted, HCV is characterized by high genetic diversity and variability due to the lack of corrective activity of its polymerase. In addition, HCV is able to disrupt the CD4+ T cell response early in the infection and causes rapid immune depletion of CD8+ T cells as the infection progresses. Strategies for the development of a preventive HCV vaccine should take these aspects into account: in particular, an effective HCV vaccine should induce both a strong humoral immune response by inducing neutralizing antibodies targeting numerous conserved epitopes of B- and T-cells, and a cellular immune response by stimulating rapid activation of T helper 1 lymphocytes as well as CTL.
Several approaches have been adopted to develop an effective preventive HCV vaccine: they can be classified based on the targeted immunity (humoral immunity, cellular immunity, or both) or the strategy used (recombinant protein or viral peptide vaccines, virus-like particle-based vaccines, DNA/recombinant vaccines, DNA/viral vector-based vaccines). DNA vaccines have the advantage of inducing cytotoxic lymphocyte responses; however, the induced immunity is often short-lived, weak and unlikely to be effective in preventing infections. Adenoviral vectors have shown the most promising results in inducing strong and broad CD4+ and CD8+ T cell responses. Vaccine strategies based on these vectors reduce peak viremia and induce protection against chronic infection in primates, but do not prevent primary HCV infection.[1] DIAGNOSTIC TOOLS IN HCV INFECTION Serological tests. Detection of anti-HCV antibodies: Several enzyme-linked immunosorbent assays (ELISAs), microparticle ELISAs, and chemiluminescent immunosorbent assays have been developed for the detection of anti-HCV antibodies. Currently, assays that include core antigens and recombinant antigens from NS3, NS4 and NS5 regions in the solid phase are widely used.
Avidity assays used to distinguish between primary and chronic or relapsing viral infection in many other diseases have also been tested in HCV infection. Although these assays can sometimes be useful for estimating the time of HCV infection after the onset of symptoms, they are nevertheless of low utility in clinical practice. [2]
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The CDC currently recommends the use of an approved screening test, either ELISA or rapid test, and the use of another assay to confirm a positive result as a true positive.
Detection of HCV antigen: In addition to the previously described tests that allow simultaneous detection of antigens and antibodies, assays have also been developed to detect HCV core antigen alone. Automated quantitative chemiluminescent immunoassays are now available with sensitivities and specificities of 80% to 99% and 96% to 99%, respectively. Several studies have demonstrated that the test can equally detect and quantify all genotypes and that HCV core antigen quantification shows good correlation with HCV RNA levels.
Molecular tests. Detection of HCV RNA: HCV RNA is detected in plasma and serum 1 -3 weeks after infection, approximately 1 month before the appearance of anti-HCV antibodies, and is a sign of ongoing viral replication. Nucleic acid testing (NAT), used to detect and quantify HCV RNA, is the gold standard for HCV diagnosis and can be performed by polymerase chain reaction (PCR), branched DNA (bDNA) signal amplification and transcription-mediated amplification. Currently, all NTCs for HCV RNA detection and quantification are standardized using the WHO International Standard, and HCV RNA results are expressed in International Units (IU/ml).[1]
Determination of HCV genotype: HCV genotype, together with baseline HCV RNA levels, is considered the main predictor of SVR to antiviral therapy. In clinical practice, HCV genotype can be assessed by commercially available methods based on real-time PCR using genotype-specific probes/primers, semi-automated sequencing, and automated reverse hybridization that analyze the 5' NC region of the HCV genome, which is the most conserved region. However, analysis of the 5' NC region can lead to errors in subtype attribution, as it is not the most suitable for distinguishing subtypes. For this reason, a new version of automated reverse hybridization, the most commonly used method, analyzes both the 5' NC as well as the core region. The gold standard of genotyping is the sequencing of the NS5B region, which is able to accurately determine the genotype, with the advantage that the resulting sequence can be used for phylogenetic analysis for epidemiological purposes.[5]
NEW THERAPEUTIC ERA. To date and for many years, the peg-IFN/RBV combination, capable of eliminating the virus in approximately 50% of treated patients, has characterized the standard of care (SOC) for chronic hepatitis C virus (HCV). The recent development and availability of new molecules called DAAs are expanding the options for HCV therapy. [2]
Currently, only TVR and BOC, the first two NS3 protease inhibitors, are available and approved for use in Europe in combination with SOC in chronically infected patients with HCV genotype 1. Both drugs are linear ketoamide molecules that act on the catalytic site of the NS3/4A protease, blocking the release of HCV NS proteins required for the assembly of the viral replication complex. [4]
The efficacy of TVR and BOC was evaluated in phase III clinical trials. In total, two studies were conducted for each of them: in naïve patients with chronic HCV (advance for TVR and sprint 2 for BOC) and in patients with SOC treatment experience who failed treatment (realize for TVR and respond 2 for BOC). All these studies demonstrated a significant improvement in PFS with DAA compared to SOC. [7]
CONCLUSIONS. Hepatitis C virus (HCV) is an RNA virus that is distantly related to flaviviruses and pestiviruses. The viral genome is a linear positive-sense RNA molecule about 9.4 kilobases long. It has a single large open reading frame that encodes a polypeptide precursor of approximately 3000 amino acids. Viral isolates from different geographic regions show considerable genetic diversity; in addition, different HCV genotypes can coexist in infected individuals. [3]
HCV infection can be detected in serum by measuring HCV antibodies or by direct measurement of HCV RNA in the blood. HCV RNA measurement is the most sensitive of the currently available tests and allows for specific diagnosis in the early acute phase of infection.
Hepatitis C virus (HCV) remains a global public health problem, despite the fact that more than 95% of infections can be cured with direct-acting antiviral treatment. Resolution of viremia after antiviral therapy does not lead to protective immunity, and therefore reinfections can occur. [8]
The rapidly evolving field of DAAs is moving towards the development of interferon-free regimens with higher CER and pangenotypic activity and less susceptibility to side effects. However, the emergence of RAV remains an important problem.
References
1. Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 2014; 20(29): 9633-9652 [PMID: 25110404 DOI: 10.3748]
2. Filippo A., Andrea O., Laura S., Bianca B., and Giancarlo I. Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol. 2014 Aug 7; 20(29): 9633-9652. [PMCID: PMC4123355 PMID: 25110404]
3. Doris B. Strader, Leonard B. Seeff. Hepatitis C : A Brief Clinical Overview. 01 April 2001/ILAR Journal, Volume 42, Issue 2, 2001, Pages 107-116,
4. R D Aach 1, C E Stevens, F B Hollinger, J W Mosley, D A Peterson, P E Taylor, R G Johnson, L H Barbosa, G J Nemo. Hepatitis C virus infection in posttransfusion hepatitis. An analysis with first- and second-generation assays. PMID: 1656258 DOI: 10.1056.
5. Michael Houghton. Discovery of the hepatitis C virus. 2009. PMID: 19207970 DOI: 10.1111
6. Jason Grebely. Gregory J Dore. What is killing people with hepatitis C virus infection? 2011. PMID: 22189973 DOI: 10.1055.
7. J A Cuthbert. Hepatitis C: progress and prob-lems.// 1994 // PMID: 7834603 PMCID: PMC358339 DOI: 10.1128.
8. Maria Victoria Preciado 1, Pamela Valva 1, Alejandro Escobar-Gutierrez 1, Paula Rahal 1, Karina Ruiz-Tovar 1, Lilian Yamasaki 1, Carlos Vazquez-Chacon 1, Armando Martinez-Guarneros 1, Juan Carlos Carpio-Pedroza 1, Salvador Fonseca-Coronado 1,
Mayra Cruz-Rivera. Hepatitis C virus molecular evolution: transmission, disease progression and antiviral therapy.// 2014// PMID: 25473152 PMCID: PMC4239486 DOI: 10.3748.
UDC 616.248-036.1-053.2:575.21]-07
Shakhova O.O., Tarnavska S.I., Bukovinian State Medical University, Chernivtsi, Ukraine Pyzhyk M.A., Sukholytkyi Y.R., Kerebko D.V., Students of Bukovinian State Medical University, Chernivtsi, Ukraine DOI: 10.24412/2520-6990-2023-9168-63-64 CLINICAL, LABORATORY AND RADIOLOGICAL FEATURES OF BACTERIAL PNEUMONIA OF VARIOUS ETIOLOGIES IN PRESCHOOL CHILDREN
Abstract.
Despite the undeniable success of modern medicine in terms of instrumental and laboratory methods in the diagnosis ofpneumonia, the issue of clinical diagnosis remains relevant. This study presents data on the clinical, laboratory and radiological features ofpneumonia caused by various pathogens in children aged 1 to 6 years of age.
Keywords: bacterial pneumonia, etiology, children
Introduction. Today, community-acquired pneumonia (CAP) in children is one of the leading health problems in the world.
Community-acquired pneumonia is an acute nonspecific inflammation of the lung tissue, namely the respiratory system, based on infectious toxicosis, respiratory failure, water and electrolyte and other metabolic disorders with pathological changes in all organs and systems. The prerequisite is the immunological and functional, as well as anatomical immaturity of the child's body, and, in turn, a wide range of pathogens. [1-3]
The World Health Organization (WHO) estimates that lower respiratory tract infections (including 90% of pneumonia) cause about 20% of deaths among children under five worldwide, which according to the United Nations Children's Fund, is about 3 million. According to statistics, pneumonia most often affects children living in countries with limited resources. In Central and Northern Europe, approximately 300 out of 100,000 children and adolescents aged 0-16 years suffer from pneumonia every year. [4-7] The most common causes of infectious genesis of CAP in children are Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae. [8] CAP can be prevented by immunization, adequate nutrition and elimination of environmental factors, and the basis for successful treatment of pneumonia is the appointment of rational etiotropic therapy, namely such groups of antibiotics as: semi-synthetic penicillins, semi-synthetic penicillins with clavulanic acid, cephalosporins, macrolides, aminoglycosides of II-III generations; expectorants, antihistamines and antipyretics.[9-11]
Objective. To determine the clinical, laboratory and radiological features of pneumonia caused by pneumococcus, chlamydia and mycoplasma in children aged 1 to 6 years.
Materials and methods. We analyzed 57 clinical cases of community-acquired pneumonia caused by
such pathogens as Streptococcus pneumoniae, Myco-plasma pneumoniae and Chlamydia pneumoniae in children from 10 months to 6 years old who were treated in the Chernivtsi Regional Children's Clinical Hospital in 2013-2018. Group I included patients with chlamydial pneumonia (n=22), group II - with mycoplasma pneumonia (n=19), and group III - pneumococcal etiology (n=16). For the etiologic interpretation of pneumonia, enzyme-linked immunosorbent assay and culture method were used.
Results and discussion. In the vast majority of cases, the disease began acutely with the development of fever (in 79% of children in group I, 70.3% in group II and 75.8% in group III), cough (in all subjects in group I, 84.8% in group II, and 86.2% in group III). At the onset of the disease, cough was mostly nonproductive (in 73.7% of cases in group I, 70.7% in group II, and 56.7% in group III). Some children had complaints of breathing difficulties due to bronchial obstruction (22.7% of patients in group I, 18% in group II and 33.5% in group III). A quarter of all patients on admission to inpatient treatment had a severe condition due to respiratory failure and intoxication syndrome (14.5% in group I, 24.7% in group II, and 42.3% in group III). At the time of admission, wheezing was absent in children of group III (35%) compared to groups I (19%) and II (26.8%). The majority of patients had leukocyto-sis, a left shift in the leukocyte count, lymphopenia, and an accelerated ESR in the complete blood count. According to the X-ray examination, focal forms of pneumonia prevailed in groups I and II (62% and 58%, respectively), and focal and draining forms in group II (59.8%).
Conclusions. At present, it is difficult to differentiate the clinical picture of CAP caused by pneumococ-cus, mycoplasma and chlamydia in children under 6 years of age. Pneumococcal pneumonia is more often more severe than mycoplasma and chlamydia pneumo-
