Научная статья на тему 'Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C'

Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C Текст научной статьи по специальности «Клиническая медицина»

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European science review
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CHRONIC HEPATITIS C / ANTIVIRAL THERAPY FOR HEPATITIS C / VIRUS GENOTYPE / INTERLEUKIN-28 / GENETIC PREDICTORS

Аннотация научной статьи по клинической медицине, автор научной работы — Nabieva Umida Pulatdjanovna, Ismailova Adolat Abdurahimovna, Adilov Djamshid Gayratovich

Complete the pathological infectious process in chronic viral hepatitis C, leading to cirrhosis and HCC is possible using antiviral therapy. The effectiveness of an antiviral therapy is influenced by various factors and the virus and the body. In this study, we obtained evidence that the genotype of hepatitis C virus genotype and IL-28B gene are independent and reliable factors predictive of SVR

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Текст научной работы на тему «Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C»

Table 1. - Dynamics of echocardiography and 6-MWT indexes in patients with unstable angina after surgical revascularization subject to background DM (DM+ group is in numerator n = 18; DM- group is in denominator; n = 16)

LV EDV, ml LV EF, % LA, mm 6-MWT, m

initialy 144.78 ± 7.89 53.33 ± 1.56 39.06 ± 1.37 259.00 ± 25.66

131.50 ± 8.39 56.13 ± 1.74 34.75 ± 1.61* 308.63 ± 21.35

After CABG 169.89 ± 9.25A 50.33 ± 1.11A 42.28 ± 1.43 223.33 ± 13.34

143.00 ± 5.68* 53.25 ± 2.10 37.88 ± 1.70* 357.50 ± 24.76***

6 months 140.06 ± 8.78### 57.94 ± 1.39AA### 36.28 ± 1.04## 433.33 ± 32.69AAA###

119.88 ± 5.77# 62.19 ± 1.32*AA### 32.56 ± 1.15*## 491.25 ± 16.89AAA###

Relative dynamics of indexes

% after CABG 22.50 -5.00 11.46 -3.29

11.90 -3.31 10.72 26.52

% 6 months -2.636 9.448 -5.684 93.240

with initial -2.521 11.899 -4.778 67.988

% 6 moths with -14.19 15.40 -12.93 112.76

CABG -13.65 19.02 -12.17 47.39

Note: * — significance of difference between groups DM+ and DM-; A — significance of difference with initial data; # — significance of difference with post-operative data (1 week after surgical revascularization); one sign — p < 0.05, two signs — p < 0.01, three signs — p < 0.001

References:

1. Maier B., Thimme W., Kallischnigg G., Graf-Bothe C., Rohnisch J. U., Hegenbarth C., Theres H. Berlin Myocardial Infarction Registry. Does Diabetes Mellitus Explain the Higher Hospital Mortality of Women with Acute Myocardial Infarction? Results from the Berlin Myocardial Infarction Registry//J Investig Med. - 2006 Apr. - 54(3): 143-151.

2. Kakorin S. V., Shashkova L. S., Mkrtumyan A. M. Acute coronary syndrome in patients with carbohydrate metabolism disorders// Heart. - 2012. - 11(1): 8-12.

3. Task Force Members, Lars Ryden et al. Guidelines on diabetes, pre-diabetes, and cardiovawscular diseases: executive summary//Eur Heart J. - 2007. - 28: 88-136.

4. DeFronzo R. A. International Textbook of Diabetes Mellitus. 3 ed. - Chichester, West Sussex; Hoboken, NJ; John Wiley. - 2004.

5. American Diabetes Association. Standards of medical care in diabetes//Diabetes Care. - 2005. - 28 (Supp. 1): S. 4-36.

Nabieva Umida Pulatdjanovna, Immunology Institute of Science Academy of the Republic of Uzbekistan, Scientific Secretary, Laboratory of Immunopathology and immunopharmacology

E-mail: Inf-ledi@mail.ru

Ismailova Adolat Abdurahimovna,

Adilov Djamshid Gayratovich

Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C

Abstract: Complete the pathological infectious process in chronic viral hepatitis C, leading to cirrhosis and HCC is possible using antiviral therapy. The effectiveness of an antiviral therapy is influenced by various factors and the virus and the body. In this study, we obtained evidence that the genotype of hepatitis C virus genotype and IL-28B gene are independent and reliable factors predictive of SVR.

Keywords: Chronic hepatitis C, antiviral therapy for hepatitis C, virus genotype, interleukin-28, genetic predictors.

Introduction

The actuality of the problem of chronic virus Hepatitis C (HCV) is explained by the high prevalence, the defeat of the most socially active groups in population, high costs and limited effectiveness of treatment, as well as projected in the nearest 20 years with significant increase of patients with cirrhosis and liver cancer [1, 27-36].

To prevent the development of liver cirrhosis and hepatocellular carcinoma also to suspend the progression of the disease allows the eradication of the infectious agent with using antiviral therapy (AVT). It is well known that the low effectiveness of an antiviral

therapy is primarily associated with virus factors as genotype 1, high viral load, the absence ofviremia reduction after 4 weeks after the AVT and liver fibrosis [3, 237-244; 5, 1219-1225].

The polymorphism of interferon-^ (IFN-X3) is the most significant genetic factors that influence the effectiveness of the therapy at the patients. In 2009, three independent groups of researchers conducting genome-wide comparison on numerous groups of patients who achieved and not achieved a sustained virologic response (SVR) during AVT have shown that a single nucleotide polymorphism with the IL-28B gene is associated with a high probability of

Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C

success in the treatment of [4, 399-401; 6, 63-68]. IL-28B gene encodes recently opened IFN-X.3, allelic variants of polymorphic loci influence the probability of spontaneous elimination of HCV in the acute phase of infection [3, 237-244].

There was identified four single -nucleotide polymorphisms with gene IL-28B, but only three of them shows the effect on SVR in ATV. Nowadays the most studied is the role of the two polymorphic loci: rs12979860 and rs8099917 gene IL-28B in different ethnic groups of patients with Hepatitis C [4, 399-401; 7, 1100-1104]. The molecular mechanism of the association of these polymorphisms with the probability of ATV by the patients during therapy is not installed.

Therefore, the aim of our research is the comparative characteristics of the group patients with chronic hepatitis C with different response to antiviral therapy taking into account the virus factors.

Tools and methods

There was examined 128 patients with chronic hepatitis at the age from 16 to 58 years (average age 35.6 ± 2.8), 37.6 % from them were males and 62.3 % were women. Approximate disease duration, defined on the basis of collection of the epidemiological history ranged from 1 year to 10 years (avarage 3.8 ± 1.1 years). 25.6 % cases of patients were unable to specify the epidemiological factors that led to the infection of hepatitis C.

Complex initial evaluation included the traditional set of clinical and biochemical laboratory parameters, USD, study of serological markers (anti-HCV-IgG). The PCR method for determination of RNA-HCV in blood was used at the patients. HCV genotypes (1a, 1b, 2a, 2b, 3a, 4) and the nucleotide polymorphism of IL-28B ware determined by PCR technique using specific primers in a human genomic Laboratory Immunology Institute of academy of science of the Rep. of Uzbekistan. The diagnosis was verified on the results of clinical and laboratory data (Health Ministry of the Rep. of Uzb. order number 560 from 30.10.2000).

Results and discussion

In the process of study of genotypic features of hepatitis C virus among patients there was revealed at 73.5 % cases the genotype 1a or 1b, at 20.6 % — 3a genotype and at 5.9 % — 2a or 2b genotypes ofhepatitis C. High viral load was observed in 88.5 % of the patients and moderate viral load was obtained in 11.5 % of patients. Severe biochemical activity was observed at 29.6 % patients, while 70.4 % has showed moderate and the minimum degree of biochemical activity of the pathological process.

According to the of genotyping results gene nucleotide polymorphism IL-28B was exhibited by the follow combinations: locus rs12979860: C/C — 29.4 %, C/T — 64.7 %, T/T — 5.9 %, and the locus rs8099917: T/T — 68.5 %, T/G — 31.5 %, G/G was not detected. Thus, rs12979860 locus genotype C/T — observed in 64.7 % cases, locus rs8099917 genotype T/T was determined at 68.5 % cases and considered as the most common genotypes among IL28B investigated patients with HCV.

The next stage of our study was to examine the nucleotide polymorphism of IL-28B in groups of patients with different response to the OEM. Patients with HCV who have completed the course OEMs and observed in the dynamics of the OEM and 6 months after completion of treatment, were conditionally divided into 2 groups: patients with SVR and patients without SVR, i. e. Patients who within 6 months after the completion of the HTP relapsed.

In the study of the distribution of the occurrence of variants of nucleotide polymorphism of IL-28B in compered groups there was determined that in group of patients with SVR rs12979860 locus genotype the most common genotype was C/C, which is found in

71.4 % of cases, genotype C/T met in 33.3 % of cases, and genotype T/T — 14.3 %; rs8099917 locus was the most frequent genotype T/T (in 90.0 % of cases), genotype T/G met in 10.0 % of cases.

In patients without SVR most frequent genotypes for the two loci were genotype C/T (87.5 %) and T/G (62.5 % cases) respectively. The difference between these data between compared groups were statistically significant (P < 0.05).

In monitoring of haplotypic combinations of loci rs12979860 and rs8099917 in investigated groups, there was noted the predominance of haplotype CC/TT in the group with SVR and the predominance of haplotype CT/TG in the group without SVR.

We have also examined the clinical and virological parameters in comparable groups of the patients. The clinical picture in patients compared groups were observed asthenovegetative (in 84.7 % of cases in patients with SVR and in 76.2 % of cases in the group ofpatients without SVR), dyspeptic (3.5 % and 6.8 %, respectively) and mixed (12.8 % and 15.4 %, respectively) syndromes. Artralgic syndrome was observed only in patients without SVR in 3.2cases. In comparable groups of patients had verified the several degrees of biochemical activity of the organism, moderate and severe biochemical activity was noted in 31.5 % of patients with SVR and in 22.6 % of patients without SVR. Minimum and low degree of biochemical activity was observed in 68.5 % and 77.4 %, respectively. As can be seen from the data presented significant difference for the presentation is not marked.

In the study of the genetic characteristics of the hepatitis C virus in two groups there was noted that one genotype were significantly more frequent in the group of patients without SVR (in

76.5 % of cases) in comparing with the group of patients with SVR (57.9 % of cases) (P < 0.05). The genotype 3 was observed significantly more frequently in patients with SVR (32.1 % versus 12.6 %, respectively) (P < 0.05). The genotype 2 in the two groups met in the same rate (9.1 % and 11.0 %, respectively).

Conclusions

The findings indicates to genetic factors including genotype ofvi-ral hepatitis C and genotype IL-28B gene which are independent and reliable factors predictive of SVR and conduct a comprehensive survey to determine the patient's genotype. Using of IL28B will take personalized treatment algorithm accordance to standard PVT course which will allow to achieve higher effectiveness of therapy.

References:

1. Sapronov G. V., Nikolaeva L. I. New prospects for personalized therapy for chronic hepatitis C//Epidemiology and Infectious Diseases. - Moscow, 2013. - № 3. - S. 27-36.

2. Ank N. et al. An impotant role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity//J. Immunol. - 2008. -180: 2474-2485.

3. Fried M. W. Side effects of therapy of hepatitis C and their management//Hepatology. - 2002. - 36: 237-244.

4. Ge D., Fellay J., Thompson A. J. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance//Nature. -2009, Sep. - 17; 461(7262): 399-401.

5. Kim Ray W. Global epidemiology and burden of hepatitis C//Microbes. Infect. - 2002. - 4: 1219-1225.

6. Sheppard P. et al. IL-28, IL-29 and their class II cytokine receptor IL-28R//Nat. Immunol. - 2003. - 4: 63-68.

7. Suppiah V., Moldovan M., Ahlensiel M. et.al. IL-28B is association with response to chronic hepatitis C Interferon-alfa and ribavirin therapy//Nature Genet. - 2009. - № 41. - P. 1100-1104.

Nasimova Nigina, Samarkand State Medical Institute E-mail: ms.rigina83@mail.ru

Evaluation of women's life quality with genital prolapse before and after surgery

Abstract: Abstract cites the results of evaluation of life quality of reproductive age women with genital prolapse before and after surgical treatment with simultaneous voluntary surgical contraception (VSC). Keywords: genital prolapse, life quality.

Introduction

Under current conditions, considering the tendency to "rejuvenation" of the disease, genital prolapse appears not only medical, but also personal, family, social problem, affecting the sexual, professional, and many other spheres of patients' life, i. e. this pathology affects the quality of patients' life.

In the diagnosis of genital prolapse the main symptom is a detected neoplasm by the patient, which protrudes beyond the vulvar cleft [13; 16; 67; 79; 80]. The most common complaints ofpatients with genital prolapse are aching and/or feeling of heaviness in the abdomen, whites, foreign body sensation in the vagina, urinary incontinence and gases during exercise, coughing, sneezing, sexual dysfunction. On genital prolapse (GP) sexual life is possible only after reduction of fallen body [149; 157].

It was found that on urinary incontinence life quality loss consists up to 50 %, with urgency and mixed — up to 80 % [48; 54]. About 37 % of US women experience incontinence symptoms, 86 % of them noted a significant deterioration in life quality [13]. With the development of new surgical techniques in urogynecology, appears a need of rigorous evaluation of the results of the intervention, so as the development of modern methods of treatment are not always aimed at improving the life quality and reducing the probability of disease recurrence [10]. In this study, the question life quality (LQ) acts as forecast criteria, planned treatment, evaluation of the effectiveness of the treatment, the analysis of early and late rehabilitation.

Assessment of LQin the surgery is usually performed before and after surgery, which is an important criterion for the effectiveness of surgical intervention [81]. Practically, there are not works dedicated to women life quality section after correction of genital prolapse in conjunction with simultaneous VSC. Due to the development of new surgical techniques is appears a necessary to a strict evaluation of intervention results. Development of new methods of treatment in surgical practice do not always aims to increase survival or decrease the probability of disease recurrence [81, 92, 102]. The level of patients' LQ, established prior to surgery has prognostic value, and helps to provide useful additional information about the patient, allowing a different position to estimate the potential results of the upcoming surgery. As a result, on the basis of risk analysis and the use of a surgical correction the overall treatment strategy for a patient is determined. In the available literature data on the LQ in patients with O and VVPO are fragmentary, due to a small number of studies of this problem, and rather narrow implementation of the proposed questionnaire for the study of LQin daily practice. A certain negative role in the assessment of the quality of life plays a specificity of some of the issues affecting the intimate side of life

(sexual function). These questions are not acceptable for some patients, especially the older age group [39; 47; 154; 166; 201; 224].

Objective

To evaluate women life quality with genital prolapse before and after surgical intervention.

Materials and methods

The study of quality of life of patients with genital prolapse and simultaneously VSC produced in accordance with the information collected as a result of a questionnaire before and after surgery at 1 year. For comparison was recruited control group of 50 women without prolapsed, similar age composed 35.2 ± 3.2 years (control group).

It was used qualimetric method with application of questionnaire "Short Form 36 Health Quality Survey" (hereinafter — SF- 36), which allows to specify eight main indicators of LQ, presented in the form of points, taking into account the fact that a higher score indicates a better quality of life, except pain index. The method recommended by the WHO (1996) to quantify the basic parameters of quality of life (emotional sphere, the sphere of physical, general well-being):

1) general health (GH) — assessment of patients health status at the moment of treatment and prospects;

2) physical functioning (PF) — reflects the degree to which health limits in the implementation of physical activity (self-care, walking, climbing stairs, carrying heavy loads, etc.);

3) role-physical functioning (RFF) — impact on the physical condition of role functioning (work, perform everyday activities);

4) role-emotional functioning (REF) — the impact on the emotional state of role functioning, involves assessment of the degree to which emotional state obstructs the work or other daily activities (including an increase in the cost of time, reducing the amount of work done, impairment of quality of its performance and the like);

5) social functioning (SF) — social functioning, is defined by the degree to which physical or emotional state limiting social activity (communication);

6) pain intensity (PI) — the severity of pain and impact of pain on the ability to engage in daily activities, including work at home and outside the home;

7) the viability (V) — means feeling full of strength and energy, or, on the contrary, exhausted;

8) mental health (MH) — self-assessment of mental health, which characterizes the mood (the presence of depression, anxiety, an overall positive emotions).

To assess sexual function on genital prolapse was used a PISQ questionnaire (Pelvic organ prolapse/urinary incontinence sexual function questionnaire).

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