genomed - analyzes and prices. Basic research Genetic typing of interleukin il 28b

As studies of recent years have shown, genetic factors, especially polymorphisms of the interleukin 28B gene, have a special effect on the result of treatment, as well as the possibility of self-recovery in case of infection.

Interleukin 28B is a representative of lambda interferons, or type 3 interferons, which have a strong antiviral effect and suppress the replication of the hepatitis C virus. Polymorphisms of the interleukin 28B gene associated with a sustained virological response were studied. With certain genotypes, a sustained virological response is achieved 2 times more often. The main role in hepatitis C infection is played by two single nucleotide substitutions:

Cytosine to thymine substitution (C>T) designated rs12979860 in the dbSNP database of the National Center for Biotechnological Information (NCBI).

Substitution of thymine for guanine (T>G), having the designation rs8099917

Depending on the nucleotides in these loci, alleles C (cytosine), T (thymine), G(guanine) and the corresponding genotypes were identified: for the rs12979860 allele - CC, CT, TT, as well as TT, TG, GG for the rs8099917 alleles. that the interleukin 28B genotype is an independent and most significant factor influencing the frequency of early and sustained virological response to AVT (antiviral therapy) among other prognostic factors. At the same time, rs12979860 polymorphisms are responsible for obtaining a response, and rs8099917 apolymorphisms are closely associated with a lack of response to AVT. Based on this, the following algorithm is recommended examinations in preparation for treatment.

Determination of the patient's genotype by IL28B can change the treatment decision algorithm by changing the duration of both the standard course of PEG IFN/RIB therapy and the duration of triple therapy for CHC. Optimization of therapy will avoid many additional problems in the treatment of patients with a high probability of a positive response to therapy (to avoid additional side effects and additional costs for triple therapy, including protease inhibitors - telaprevir and boceprevir)

Determination of the patient's genotype by IL28B can change the treatment decision algorithm by changing the duration of both the standard course of PEG IFN/RIB therapy and the duration of triple therapy for CHC. Optimization of therapy will avoid many additional problems in the treatment of patients with a high probability of a positive response to therapy (avoid additional side effects and additional costs for triple therapy, including protease inhibitors - telaprevir and boceprevir)

2

1 FBSI "Federal Scientific Center for Preventive Health Risk Management Technologies of Rospotrebnadzor"

2 SBEE HPE "Perm State Medical Academy. ak. E.A. Wagner" of the Ministry of Health of Russia

3 State Health Institution "Regional Clinical Infectious Diseases Hospital"

Purpose of the study. To study the relationship between laboratory markers of cytolysis, cholestasis, fibrosis, liver regeneration and polymorphism of the interleukin 28B (IL28B) gene in the rs12979860 region in patients with chronic hepatitis C (CHC). Material and methods. 100 CHC patients and 90 healthy donors were examined. In the blood serum, liver function tests, the concentration of hyaluronic acid, alpha-fetoprotein by enzyme immunoassay, the level of viral load and polymorphism of the IL28B gene (rs12979860) were evaluated by polymerase chain reaction. Results. Cytolysis and cholestasis syndromes were revealed in patients with CHC, and the median concentration of hyaluronic acid and alpha-fetoprotein was more than 2 times higher than the levels of these indicators in the control group (p = 0.004 and p = 0.0001). In general, there was no statistically significant difference in the frequencies of genotypes and alleles of IL28B (rs12979860) between groups of healthy individuals and patients with CHC. Nevertheless, 71.4% of patients with hepatitis had an unfavorable combination of CT and TT genotypes and, accordingly, a potential risk of developing a negative response to antiviral therapy with its maximum manifestation in TT homozygotes. In a correlation analysis, the minor allele T of the IL-28B gene showed significant relationships with alanine (r = 0.25, p = 0.02) and aspartic (r = 0.22, p = 0.019) transaminases, direct bilirubin (r = 0.019, 25, p = 0.02), hyaluronic acid (r = 0.17, p = 0.03), alpha-fetoprotein (r = 0.25, p = 0.02), viral load (r = 0, 25, p = 0.021). Conclusion. Polymorphism of the IL-28B gene is associated with the severity of liver damage in CHC patients.

chronic hepatitis C

interleukin 28B gene polymorphism

cytolysis syndrome

cholestasis

hyaluronic acid

alpha-fetoprotein

1. Abdurakhmanov D.T. Prospects in the treatment of chronic hepatitis C // Clinical hepatology. - 2010. - No. 3. - P. 3–9.

2. Simankova T.V., Garmash I.V., Arisheva O.S., Manukhina N.V. IL-28B gene polymorphism as a predictor of response to antiviral therapy for chronic hepatitis C. Klin. pharmacol. ter. - 2012. - No. 21 (1). – P. 17–22.

3. Shchekotova A.P. Interrelation of markers of endothelial dysfunction and liver fibrosis with viral load in chronic viral hepatitis C // Modern problems of science and education (electronic journal). 2012. No. 1. URL: www.science-education.ru/101-5458.

4. Agúndez J.A., García-Martin E., Maestro M.L., Cuenca F., Martínez C., et al. Relation of IL28B Gene Polymorphism with Biochemical and Histological Features in Hepatitis C Virus-Induced Liver Disease. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037998.

5. Eurich D., Boas-Knoop S., Bahra M., Neuhaus R., Somasundaram R., Neuhaus P., Neumann U., Seehofer D. Role of IL28B polymorphism in the development of hepatitis C virus-induced hepatocellular carcinoma , graft fibrosis, and posttransplant antiviral therapy. Transplantation/ 2012 Mar 27;93(6):644–9.

6. Ge D., Fellay J., Thompson A. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance // Nature. 2009 Vol. 461. pp. 399–401.

7. McCarthy J., Li J., Thompson A. Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin // Gastroenterology. 2010 Vol. 138. pp. 2307–2314.

8. Moliner L., Pontisso P., De Salvo G.L. et al. Serum and liver HCV RNA levels in patients with chronic hepatitis C: correlation with clinical and histological features // Gut. 1998. Vol. 42. pp. 856–860.

9. Perz J., Armstrong G., Farrington L. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide // J. Hepatol. 2006 Vol. 45(4). rr. 529–538.

10. Statermayer A.F., Stauber R., Hofer H., Rutter K. et al. Influence of the IL28B genotype on early and sustained virologic responses in previously untreated patients with chronic hepatitis C. Clinical gastroenterology and hepatology. 2011. V. 4. No. 3. http://health.elsevier.ru / journals.

11. Thomas D.L., Thio C.L., Martin M.P. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus // Nature. 2009 Vol. 461(7265). rr. 798–801.

Viral hepatitis C is one of the socially significant diseases and is one of the main causes of chronic liver disease. The WHO estimates that 170 million people, or 3% of the population, are infected with hepatitis C virus (HCV) worldwide. Currently, the "gold standard" of antiviral therapy for chronic hepatitis C (CHC) is pegylated interferon in combination with ribavirin. Combined antiviral therapy provides a stable virological response in an average of 50-60% of patients with chronic hepatitis C, including 40-50% of patients with HCV genotype 1 and 70-80% with genotypes 2 and 3. Individual approach to treatment, timely prevention and correction of adverse events increase the effectiveness of treatment, but in almost 40% of cases, antiviral therapy is ineffective. A genetic marker has appeared that makes it possible to partly predict its outcome: the polymorphism of the interleukin 28B gene (IL28B) determines to a certain extent the sensitivity of the patient's immune system to stimulation with interferon.

In 2009, D. Ge et al. found a single nucleotide substitution in IL28B on chromosome 19, which, taking into account localization, was designated as rs12979860. Depending on the nitrogenous base located in this locus, 2 alleles were isolated: rs12979860 C (cytosine) and rs12979860 T (thymine). Based on the combination of alleles, 3 genotypic variants of the IL28B gene polymorphism are possible: CC, CT, and TT. Depending on the frequency in the population, the rs12979860 C allele is a major one; occurring more often, and the rs12979860 T allele is minor. It has been proven that the frequency of a positive response to antiviral therapy is higher in patients with rs12979860 CC genotypes (70.5%) and lower in patients with rs12979860 CT and TT genotypes (32.0% and 23.3%, respectively). The carriage of the T allele, which increases the likelihood of a negative response to antiviral therapy, is more important than the "protective effect" of the C allele. Nevertheless, the CC genotype contributes to the elimination of the virus. Determination of the IL28B gene polymorphism made it possible to predict the probability of achieving a sustained virological response with a sensitivity of 65% and a specificity of 78% for the rs12979860 marker of this gene.

Determination of the genetic polymorphism of this marker is of greatest importance for patients with HCV genotype 1, given the lower response rate to standard antiviral therapy. Some studies have not found a clear relationship between IL28B polymorphism and sustained virologic response rates in these patients. Determining the IL28B genotype is of great importance in assessing the potential response to antiviral therapy and in selecting patients who can benefit from shorter courses of treatment. In general, IL28B polymorphism is one of the factors that make it possible to individualize the treatment of chronic hepatitis C. There is evidence in the literature that the IL28B gene polymorphism is associated with the development of HCV-induced hepatocellular carcinoma. Thus, it seems interesting to study the relationship of this gene polymorphism with the severity of liver damage, in particular, with abnormal liver function tests, laboratory tests of fibrosis and liver regeneration, which will help clarify the role of IL28B polymorphism in the pathogenesis and progression of CHC.

The aim of the study was to study the relationship between laboratory markers of cytolysis, cholestasis, hyaluronic acid (HA), alpha-fetoprotein (AFP), viral load (VL) and IL28B genetic polymorphism in the rs12979860 region in CHC patients.

Materials and methods of research

We examined 100 patients with CHC in the reactivation phase, hospitalized in the Perm Regional Infectious Diseases Clinical Hospital to start combined antiviral therapy. The mean age of the patients was 38.3 ± 10.4 years, of which 48 were men and 52 were women. Etiological verification of the diagnosis was carried out by qualitative and quantitative determination of HCV RNA in the blood of patients using polymerase chain reaction (PCR), as well as HCV serological markers. According to the HCV genotype, patients with CHC were divided as follows: genotype 1 was determined in 56% of patients, genotype 2 and 3 - in 44%. A sex-matched control group included 90 apparently healthy (donors) individuals with an average age of 36.3 ± 7.9 years without liver disease.

Biochemical parameters in blood serum were determined on an automatic analyzer "Architect-4000" (USA). The level of HA - a direct marker of liver fibrosis - in the blood serum was assessed using the BCM Diagnostics kit by enzyme immunoassay on the Stat-Fax analyzer (USA) in 76 patients. The concentration of AFP in blood serum was studied by immunochemiluminescent analysis using the AFP kit (Siemens) on the Immulite-1000 analyzer (Germany) in 44 patients. In the control group, the concentration of HA and AFP was studied in 20 practically healthy individuals.

Allele-specific PCR with real-time product detection was used to identify polymorphic variants of the rs12979860 marker of the IL28B gene. The design of primers and probes was carried out by employees of CJSC Syntol (Moscow). (USA). To determine the genotypes of this gene in all patients with CHC and 90 healthy donors, DNA was isolated from whole venous blood, previously stabilized with EDTA.

Statistical processing of the obtained results was carried out using the Statistica 7.0 program (StatSoft). The distribution of results was checked according to the Kolmogorov–Smirnov criterion. To describe the obtained quantitative characteristics, the data were presented as a median (Me) and 25th and 75th percentiles, minimum (min) and maximum (max). Since the distribution of GA and AFP values ​​deviated from normal, the nonparametric Mann–Whitney test was used to assess the significance of differences between independent groups. To describe the ratio of frequencies of genotypes and alleles of genes, the Hardy–Weinberg equilibrium was used. The studied groups were in an equilibrium (stable) state in terms of the genotype frequencies of the studied gene (p > 0.05). Differences in two populations were calculated by odds ratio (OR) using a case-control approach for various inheritance patterns: additive, common, multiplicative, dominant, and recessive, and were considered significant at p< 0,05. Количественная оценка линейной связи между двумя независимыми величинами определялась с использованием коэффициента ранговой корреляции по Спирмену (r). Значимость взаимосвязей и различия между выборками считались достоверными при значении для р < 0,05.

Research results and discussion

Taking into account the biochemical parameters of blood in patients with CHC, a syndrome of cytolysis was detected, which was characterized by an increase in the activity of alanine (ALT) and aspartic transaminases (AST) in the blood serum, mesenchymal inflammatory syndrome (an increase in thymol test) and cholestasis syndrome (an increase in the activity of alkaline phosphatase, direct bilirubin).

In the group of patients with CHC, an increased content of HA was noted, which reflects the activation of fibrosis against the background of chronic inflammation of the liver, while the median concentration of HA in the blood was 2 times higher than the level in the control group (p = 0.01) (Table 1). The concentration of AFP as a marker of hepatocyte regeneration in CHC patients was also significantly higher than in the control group.

Viremia in patients with CHC showed large variations in VL. The level of VL in patients in 70% was high - above 2∙106 copies/ml, in 30% of cases low - below 2∙106 copies/ml. At the same time, the minimum viremia was 0.022∙106, the maximum - 8800∙106 copies/ml. The variability of viremia in the group of those examined during CHC reactivation is consistent with the literature data.

Table 1

Hyaluronic acid and alpha-fetoprotein in CHC patients and in the control group

Note. p - the significance of the differences in the indicator in the studied groups was calculated using the Mann-Whitney test.

In the present study, we analyzed a single nucleotide substitution (SNP) in the IL-28B gene (rs12979860) in 190 individuals (90 donors without chronic liver disease and 100 patients with CHC).

The prevalence of homozygotes for the C allele (CC) in the group of healthy and CHC patients did not differ significantly (χ2 = 0.61; p = 0.44) and amounted to 42 and 36%, respectively (figure). The incidence of pathological TT homozygotes in the group of healthy and CHC patients was 6% and 8%, respectively (χ2 = 0.35; p = 0.55). In both groups, ST heterozygotes predominated (χ2 = 0.79; p = 0.67). The ratio of allele frequencies of the studied marker in the studied groups was also not characterized by a difference. The incidence of the pathological minor allele T in the CHC group was 36%, in the control group 32% (χ2 = 0.64; p = 0.42). The results obtained on the occurrence of genotypes and alleles of IL-28B (rs12979860) both for healthy individuals and in the CHC group among the population of the Perm Territory practically do not differ from the data of other authors. In particular, in Russia, the prevalence of the protective allele C in the population is 61-64%, in our studies - 64% in patients with CHC and 61% in the control group. Thus, during the study, no statistically significant difference was found in the frequencies of genotypes and alleles of the IL-28B marker (rs12979860) between groups of healthy individuals and individuals with CHC. In the group of patients with CHC, the frequency of the risk allele T was 0.359, which did not significantly differ from its frequency of 0.319 among healthy people. Of the 56 patients infected with HCV-1, 40 people had an unfavorable combination of rs12979860 CT and TT genotypes (35 and 5, respectively), which significantly differed from the control group (χ2 = 4.55; p = 0.03). Thus, the potential risk of developing an unstable virological response with HCV genotype 1 was 71.4%.

The prevalence of genotypes and alleles of the polymorphism of the IL-28B gene (rs12979860) in CHC patients and in the control group

In the correlation analysis, the minor allele T of the IL-28B gene (rs12979860) showed significant correlations with functional liver tests: ALT, AST, total and direct bilirubin, which indicates the relationship between the gene polymorphism and the severity of liver damage. These data also indicate an unfavorable effect of the severity of cytolysis and cholestasis on the prognosis of antiviral therapy (Table 2). The results obtained are consistent with the data of the Agundez J.A. study. et al. (2009), who revealed the relationship of gene polymorphism with ALT, gamma-glutamyl transpeptidase, AST/ALT ratio.

table 2

Relationships of the minor allele T of the IL-28B gene (rs12979860) with functional liver tests, hyaluronic acid and alpha-fetoprotein in CHC

Notes: r - the relationship of indicators; p is the significance of the correlation.

A positive significant correlation between the T allele and HA indicates that the studied gene can be assessed as a factor in the progression of liver fibrosis. The correlation with AFP also suggests an association of the gene polymorphism with more pronounced liver damage and the risk of hepatocarcinoma. Eurich D. et al. (2012) found an association between IL-28B and AFP in hepatocarcinoma associated with CHC and with the progression of fibrosis in patients with HCV infection after liver transplantation. The relationship of the T allele with the level of VL may indicate a more severe damage to hepatocytes in patients with CHC, which is consistent with the identified relationship between HA and the degree of viremia. In general, the identified relationships of the minor allele of the T gene with the studied tests indicate that the genetic polymorphism of IL-28B can be realized indirectly through a number of parameters involved in the pathogenesis of CHC and influencing the effectiveness of antiviral therapy. These factors include the presence of cytolysis and cholestasis syndromes, the severity of liver fibrosis, activation of hepatocyte regeneration, and the level of VL.

Thus, the polymorphism of the IL-28B gene (rs12979860) is associated with the severity of liver damage in CHC patients, which must be taken into account in order to decide on the optimization of treatment in case of an unfavorable combination of these factors, especially in patients with the minor T allele.

1. In patients with CHC in the reactivation phase, an increase in HA and AFP was detected, which indicates the activation of fibrosis and regeneration in the liver.

2. During the study, no statistically significant difference was found in the frequency of occurrence of genotypes and alleles of the IL-28B gene (rs12979860) between groups of healthy individuals and patients with CHC with different virus genotypes.

3. In 71.4% of patients infected with HCV-1, there was an unfavorable combination of rs12979860 CT and TT genotypes and, accordingly, a potential risk of developing a negative response to antiviral therapy with its maximum manifestation in TT homozygotes.

4. In patients with chronic hepatitis C, a correlation was found between the minor allele T of the IL-28B gene (rs12979860) and the severity of cytolysis and cholestasis syndromes, markers of liver fibrosis and regeneration, as well as the level of viremia.

5. In patients with CHC with HCV genotype 1, in order to determine the prognosis of antiviral therapy and address the issue of optimizing treatment, it is necessary to evaluate a combination of factors: the severity of cytolysis and cholestasis, the concentration of HA, AFP and the initial level of viremia, especially in patients with the minor allele T of the IL-28B gene .

Reviewers:

Ustinova O.Yu., Doctor of Medical Sciences, Professor, Deputy Director for Medical Work, FBSI "Federal Scientific Center for Medical and Preventive Technologies for Population Health Risk Management", Perm;

Gein SV, Doctor of Medical Sciences, Leading Researcher, Laboratory of Biochemistry of Microbial Development, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm.

The work was received by the editors on December 16, 2013.

Bibliographic link

Bulatova I.A., Krivtsov A.V., Shchekotova A.P., Larionova G.G., Shchekotov V.V. RELATIONSHIP OF THE SEVERITY OF LIVER DAMAGE WITH POLYMORPHISM OF THE INTERLEUKIN 28B GENE IN PATIENTS WITH CHRONIC HEPATITIS C // Fundamental Research. - 2013. - No. 12-2. - S. 186-190;
URL: http://fundamental-research.ru/ru/article/view?id=33301 (date of access: 02/01/2020). We bring to your attention the journals published by the publishing house "Academy of Natural History"

Method of determination Method of sequence-specific primers, PCR.

Material under study Whole blood (with EDTA)

Home visit available

HEPATITIS C is an infectious disease that, in chronically infected patients, is associated with a risk of developing liver cirrhosis and hepatocellular carcinoma. Hepatitis C virus (HCV) has several genotypes, of which the most common in our country is hepatitis C virus genotype 1.

Modern antiviral therapy for chronic hepatitis C is a combination therapy with pegylated interferon (interferon with an added polyethylene glycol molecule and a prolonged effect) and ribavirin (PEG-IFN / RBV, PEG IFN / RIB) and allows to achieve success (sustained virological response) in 40-60% patients.

Obviously, the identification of factors affecting the success of treatment, including genetic ones, is of great importance, both for a doctor who needs objective criteria for predicting the effectiveness of treatment, and for a patient who, before starting standard therapy, must be informed about the likelihood of its success. and side effects of the antiviral drugs used.

Genetic variants associated with the functions of certain cytokines affect the individual characteristics of the immune response to a given infection. IL28B is an interferon-λ-3 and is a class II cytokine receptor ligand. These ligands trigger the JAK/STAT signaling cascade, activating the synthesis of 2',5'-oligoadenylate synthetase, which activates the endonuclease. Endonuclease, in turn, is involved in the processes of stimulating the formation of the protein kinase enzyme, which blocks the synthesis of viral proteins.

It has been shown that polymorphisms associated with the IL28B gene are associated with the probability of spontaneous elimination of HCV and response to antiviral therapy. Two substitutions play the main role: cytosine to thymine substitution (C>T) in single nucleotide polymorphism rs12979860 and thymine to guanine substitution (T>G) in single nucleotide polymorphism rs8099917.

For the single nucleotide polymorphism rs12979860, the C/C genotype is associated with twice the likelihood of a positive response to treatment with interferon and ribavirin, while the T/C and T/T genotypes at this position are associated with a lower likelihood of response to treatment. The CC genotype is predominantly detected among people with spontaneous resolution of the infection. The immune system of C/C allele carriers is more capable of defeating the virus on its own. Interestingly, with the C/C genotype, the viral load (the amount of virus in the blood) before treatment is higher than in carriers of the T/T alleles.

According to the single nucleotide polymorphism rs8099917, the T/T genotype is associated with spontaneous resolution of the infection, regardless of treatment, while the G/T and G/G genotypes at this position are associated with a lower likelihood of responding to treatment and achieving a sustained virological response. The G allele in rs8099917 is a risk allele and is associated with poor response to pegylated interferon and ribavirin therapy.

Studies of the role of genetic polymorphism in these regions of the human genome showed that the positive predictive value of IL28B polymorphism is higher than other basic characteristics used to predict the success of therapy (body mass index, age, fibrosis stage, and viral load). However, in studies on large populations of patients with chronic hepatitis with different clinical profiles (stage of liver fibrosis from 0 to 4, the initial level of viremia is low and high), it was shown that the predictive value of the patient's IL28 genotype for achieving a sustained virological response can be significantly modified depending on from clinical characteristics and decrease from 74.4% to 37.3% for patients with the rs12979860 C/C genotype. Therefore, genetic markers must be taken into account in combination with other basic characteristics of a particular patient. It has been shown that the IL28B polymorphism has the greatest value when infected with HCV subtype 1.

Determination of the patient's genotype by IL28B will help in deciding on the use of a standard course of therapy for chronic hepatitis C with PEG IFN/RIB and, if necessary, individual optimization of therapy by including protease inhibitors - telaprevir and boceprevir.

Literature

1. Internal diseases according to Tinsley R. Harrison. Practice 2005. 3388 p.

2. Ghary M.G. et al. Diagnosis, management and treatment of hepatitis C: an update. American Association for the Study of Liver Diseases. hepatology. 2009, Apr; 49(4): 1335-1374

3. Thomas D.L. et al. Genetic variation in IL28 B and spontaneous clearance of hepatitis C virus. Nature. 2009 Vol. 461, No. 7265. P. 798–801.

4. Thompson A.J. et al. Interleukin-28 B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. gastroenterology. 2010 Jul; 139(1): 120–129

5. Reagent manufacturer's materials.

Interleukin-28B (genotyping) (HCV treatment prognosis)


Analysis description:

Interleukin-28B (genotyping) - test for determining genetic polymorphisms associated with the functions of interleukin 28B by PCR (polymerase chain reaction).

Determination of a patient's genotype by IL28B can change the treatment decision algorithm by changing the duration of both the standard course of PEG IFN/RIB therapy and the duration of triple therapy for CHC. Optimization of therapy will avoid many additional problems in the treatment of patients with a high probability of a positive response to therapy (to avoid additional side effects and additional costs for triple therapy with the inclusion of protease inhibitors - telaprevir and boceprevir).

Indications

  • Viral hepatitis C.
  • Prognosis of treatment of viral hepatitis C.
  • Insufficient immunological response to the prescribed treatment.

Material for research: whole blood.

Preparation for the study: blood sampling is carried out strictly on an empty stomach (at least 8 hours after the last meal).

Result interpretation:

Polymorphism:

Possible manifestations of polymorphism

Interleukin-28B (RS8099917)

GG genotype discovered

Poor response to interferon and ribavirin therapy

TG genotype discovered

Decreased response to interferon and ribavirin therapy

TT genotype discovered

Spontaneous resolution of infection possible

Interleukin-28B (RS12979860)

CC genotype discovered

1. Possible spontaneous resolution of the infection

2. About 80% of CHC patients respond to treatment

3. High viral load is characteristic

CT genotype discovered

20-40% of CHC patients respond to treatment

TT genotype discovered

20-25% of CHC patients respond to treatment


CODE: 721
Tube color: F
Cost: 770

Please note that the prices indicated on the site may have slight deviations from the official price list.
Vladivostok and Artem now have the opportunity to take tests at home (blood sampling).
+ Research deadlines
  • Biochemical, Hematological, General clinical studies, Coagulological studies, Immunochemical - 1 business day**
  • ELISA diagnostics, PCR smears - 2 working days**
  • PCR-blood, allergy diagnostics - up to 3 business days**
  • Flow cytometry - up to 2 business days**
  • Immunological studies - up to 5 business days**
  • Bacteriological research - up to 7 business days**
  • Genetic diagnosis of biological relationship - up to 21 business days**
  • Molecular genetic blood tests without a conclusion - up to 5 business days**
  • Molecular genetic blood tests with a conclusion - up to 21 business days**
  • Highly specific immunological studies - blood sampling for immunological studies is performed every day and only in a separate tube. Examinations are carried out once a week, on Tuesdays, the result is issued from Wednesday, after 13.00 .
  • Genetic diagnostics - a complete list of studies with prices can be downloaded on the website. Studies are carried out in a third-party genetic laboratory of INTO-Steel LLC.

* * The terms of the research are calculated from the moment the material arrives at the laboratory, excluding the day the material was taken. When delivering from other hospitals, the terms may increase due to the delivery time.

+ Explanations, according to the designation of the color of the test tube
  • K - test tube with a red cap, to obtain serum;
  • F - a test tube with a purple cap, to obtain plasma and study whole blood;
  • H - test tube with a black cap, to study the level of ESR;
  • G - a test tube with a yellow cap, for the study of urine samples;
  • C - test tube with a gray cap, to determine the level of glucose;
  • Z - a test tube with a green cap, for the study of electrolytes and immunological studies;
  • G - a test tube with a blue cap, for coagulation studies;
  • B - Container for biomaterial (sterile);
  • M - smear (preparation) on a glass slide of various localizations;
  • SL - test tube to collect saliva;
  • TRS - transport liquid medium;
  • T/G – probe-tampon sterile in vitro (with gel);
  • P - film for taking scrapings for enterobiasis.
+ Collection points for biological material
PRIMORSKY KRAI
Vladivostok

Horizontal tabs

Description

It is now well established that changes in the cluster of cytokine genes (IL28A, IL28B and IL29) localized on the 19th chromosome (19q13) of a person are the main factor determining the features of the body's antiviral defense. The polymorphism in the region adjacent to the interleukin 28B (IL28B) gene is of the greatest importance. It has been shown that IL28B polymorphisms determine both the probability of spontaneous elimination of HCV and the response to interferon and ribavirin therapy.
The main role in hepatitis C infection is played by two single nucleotide substitutions:
a cytosine-to-thymine substitution (C>T) designated rs12979860 in the dbSNP database of the National Center for Biotechnological Information (NCBI).
replacement of thymine by guanine (T>G), which has the designation rs8099917
Detection of polymorphisms in the IL28B gene is the only recommended pharmacogenetic test for those infected with the hepatitis C virus. According to the Recommendations for the Diagnosis and Treatment of Adult Patients with Hepatitis C of the Ministry of Health of Russia of 2013, “determination of the patient's genotype by the totality of allelic variants of single nucleotide polymorphisms rs12979860 and rs8099917 in the interleukin 28 B gene (IL28B) in patients with HCV genotype 1 is a reliable predictor of achieving a sustained virologic response during dual and triple antiviral therapy.”
It has been shown that the IL28B polymorphism has the greatest value when infected with HCV subtype 1. Based on this, the following examination algorithm is recommended in preparation for treatment.

Single nucleotide polymorphisms (SNPs) at the rs8099917 and rs12979860 loci of the IL28B gene are associated with the frequency of spontaneous recovery in acute hepatitis C and the likelihood of achieving a sustained response in the treatment of chronic hepatitis C with interferon preparations. The favorable genotype is CC (versus CT and TT) at the rs12979860 locus and TT (versus TG and GG) at the rs8099917 locus.

Indications

Indications for appointment:

  • Predicting the outcome of the disease and response to treatment,
  • the choice between standard and pegylated interferon in combination with ribavirin for the treatment of chronic hepatitis C,
  • the choice of tactics “waiting for the availability of triple therapy with the inclusion of HCV protease inhibitors” or treatment with a standard regimen of dual therapy with interferon in combination with ribavirin for patients with additional factors (except for liver fibrosis) that reduce the likelihood of cure with drugs of the existing standard of antiviral therapy.
Interpretation of results
Loading...Loading...
Top of page