Drug acetylation plays an important role in the medical practice. Modern methods of acetylation phenotype prediction are based on genotyping of polymorphisms in the second exon of the gene
NAT2
. ...Some disadvantages of these methods limit their application in the clinical practice. We developed a method of human genotyping based on identification of
NAT2
gene polymorphism
rs1495741
by real-time PCR. This method of genotype determination has a number of advantages: high sensitivity, simplicity, possibility of automated interpretation of the results, and feasibility in clinical laboratories.
The measurement of the level of mitochondrial DNA (mtDNA) in the blood is a difficult problem due to high variability of mitochondrial genes, deletions in the mitochondrial genome in some ...pathological conditions, different sources of mtDNA into the bloodstream (mtDNA from tissues, from blood cells,
etc
.). We designed primers and TaqMan probes for highly conserved regions of the
ND1
and
ND2
genes outside the mitochondrial deletions “hot zones”. For standardizing the technique, the true concentration of low-molecular-weight mtDNA was determined by real-time PCR for two targets: a fragment of the
ND2
gene (122 bp) and the
ND1
and
ND2
genes (1198 bp). The sensitivity and specificity of the developed approach were verified on a DNA pool isolated from the blood plasma of healthy donors of various nationalities. The concentration of low-molecular-weight mtDNA in the blood plasma of two patients with COVID-19 was monitored over two weeks of inpatient treatment. A significant increase in the content of low-molecular-weight mtDNA was observed during the first 5 days after hospitalization, followed by a drop to the level of healthy donors. The developed technique makes it possible to assess the blood level of low-molecular-weight mtDNA regardless of the quality of sampling and makes it possible to standardize this biological marker in a wide range of infectious and non-infectious pathologies.
We evaluated the possibility of using an experimental model of hepatocellular carcinoma to study oncomarkers of primary liver cancer and compared the diagnostic efficacy of alpha-fetoprotein and ...osteopontin in the experiment and in clinical practice. Experimental studies were performed on a model of hepatocellular carcinoma induced by administration of diethyl nitrosamine to Fisher-344 rats. In addition, the levels of α-fetoprotein and osteopontin were determined in 35 patients with hepatocellular carcinoma detected at stages I-II according to TNM classification. The proposed model of liver cancer in rats reflects the sequence of stages characteristic of hepatocellular carcinoma in humans: liver fibrosis—cirrhosis—cancer. This model is applicable for the study of tumor markers at the early stage of tumor development. Osteopontin was found to have a more powerful diagnostic potential then alpha-fetoprotein.
was to identify the most effective serum tumor markers for early diagnosis of hepatocellular carcinoma based on the combination of diagnostic characteristics and correlations.
There were observed 55 ...patients with chronic hepatitis C in the stage of liver cirrhosis with a verified diagnosis of hepatocellular carcinoma. The control group consisted of 55 patients with chronic hepatitis C at the stage of liver cirrhosis without hepatocellular carcinoma, comparable to the experimental group in terms of basic clinical profile. The following tumor markers were estimated in both groups: alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), annexin A2 (ANXA2), heparin-binding growth factor Midkine (MDK), glypican-3 (GPC3), des-gamma-carboxyprothrombin (DCP, PIVKA-II), dickkopf-related protein 1 (DKK-1), osteopontin (OPN), and Golgi protein 73 (GP73). There were also evaluated such indices as diagnostic sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio of a positive test, the possible correlation between alpha-fetoprotein and other tumor markers. The area under the ROC curve (AUC) was calculated at the 95% confidence interval.
The greatest sensitivity was revealed when using heparin-binding growth factor, annexin A2, osteopontin. Alpha-fetoprotein, alpha-fetoprotein-L3, glypican-3, des-gamma-carboxyprothrombin, dickkopf-related protein 1 had the best specificity. AUC>0.75 was found in annexin A2, heparin-binding growth factor, glypican-3, des-gamma-carboxyprothrombin, osteopontin, Golgi protein 73. The likelihood ratio of a positive test result was the highest for glypican-3. A significant correlation was found between alpha-fetoprotein and alpha-fetoprotein-L3, annexin A2, des-gamma-carboxyprothrombin.
According to the aggregate indicators of diagnostic efficiency, heparin-binding growth factor, glypican-3, and osteopontin are the most promising tumor markers of those studied. When they are used, integral AUC values are above the average, the level of these tumor markers in the blood of patients with hepatocellular cancer does not correlate with alpha-fetoprotein. They are applicable for diagnosing liver cancer in AFP-negative patients. The combined use of AFP + GPC3, AFP + OPN has already shown their advantages. However, the efficacy of the combination of AFP + MDK, GPC3 + OPN has not been determined yet; therefore, significance of the combined use of these tumor markers in the diagnosis of liver cancer should be investigated in the near future.
Aim. To establish the main external and genetically determined risk factors for the development of hepatocellular cancer in the ethnic group of male Yakuts living in the Republic of Sakha (Yakutia) ...RS (Y) in the epidemiologically unfavorable conditions of the incidence of viral hepatitis. Materials and methods. A total of 97 male Yakuts were examined, including 44 people diagnosed with hepatocellular cancer and 53 people diagnosed with chronic viral hepatitis. HCC risk factors were identified by analyzing medical records and questioning patients. In the experimental and control groups, genetic studies of single nucleotide polymorphisms of genes mapped on the X-chromosome and involved in the activation of antiviral immunity along the TLR7 signaling pathway were performed. Results and discussion. In 100% of patients with hepatocellular cancer, infection with hepatitis B, C, D viruses or co - infection with these agents was detected. Every fourth patient with HCC in the RS (Y) was infected with hepatitis D. The course of hepatocellular cancer associated with HDV was characterized by rapid progression of liver cirrhosis, development of portal hypertension, bleeding from varicose veins of the stomach and esophagus (36.4%) and edematous ascitic syndrome (63.6%). In addition to viral agents, additional risk factors for liver cancer were identified, such as alcohol abuse, overweight, diabetes mellitus, and smoking. Among the studied variation sites of genes localized on the X-chromosome and encoding the reaction of innate antiviral immunity, no genetic marker was found with a sufficient degree of confidence determining the likelihood of hepatocellular cancer developing. Conclusions. The high incidence of hepatocellular carcinoma of the male population in the RS (Y) is due to the widespread prevalence of parenteral viral hepatitis, especially viral hepatitis D. Due to the introduction of mass vaccination of the population against hepatitis B in the Russian Federation in the foreseeable future in the RS (Y) we should see a decrease in the proportion of hepatocellular cancer associated with hepatitis B and D viruses, and therefore the focus should be on the treatment and prevention of hepatitis C virus and non - infectious risk factors.
The frequency of single nucleotide polymorphisms of IFNL3 gene (rsl12979860 and rs8099917) and dinucleotide polymorphism of IFNL4 gene (ss469415590) were estimated in healthy inhabitants of Mongolia ...and Irkutsk regions taking into account their races. Population and genetic studies were performed in 1520 conventionally healthy volunteers (blood donors), representatives of Caucasian and Mongoloid races. Significant race-related differences in the incidence of IFNL3 and IFNL4 gene polymorphisms associated with spontaneous clearance of hepatitis C virus were found in healthy volunteers.
Aim of the research
.
To study the epidemic manifestations of HCV infection in the Republic of Sakha (Yakutia) in order to develop recommendations for improving the effectiveness and quality of ...treatment and prevention measures.
Materials and methods
.
The paper uses materials from the official statistics of the Territorial Department of Rospotrebnadzor of the Republic of Sakha (Yakutia) for 1994–2018, and data from the electronic register «Chronic viral hepatitis
in the RS (Ya)» (2019). Molecular and biological studies of the genotype of the hepatitis C virus were performed jointly
on the basis of the Federal state budgetary Institution «Central research Institute of epidemiology» of Rospotrebnadzor
(2007–2011, n = 75). To assess the epidemiological situation, the rate of increase in morbidity is calculated on the basis
of data equalized by the method of least squares. Statistical processing was performed using the SPSS 17 program.
The critical significance level is assumed to be 0.05.
Results.
Thus, the study of long-term dynamics of the incidence of viral hepatitis shows that in the Republic of Sakha
(Yakutia) a consistently high level of incidence of HCV with adverse trends in the development of the epidemic process
remains. Analysis of the distribution of different variants of HCV genotypes allowed us to establish the prevalence
of genotype 1b, which can determine the high frequency of cirrhosis and primary liver cancer. The current situation
in the Republic regarding the incidence of viral hepatitis requires detailed monitoring, improvement of epidemiological surveillance and introduction of modern treatment methods. It is also necessary to improve the quality of health
education among the population of the Republic.
Relevance. In 2016, a resolution was adopted at the 69th World Health Assembly, the goal of which is to eliminate parenteral hepatitis in the world by 2030. In the Republic of Sakha (Yakutia), as in ...the Russian Federation as a whole, it is necessary to determine the starting positions for the prevalence and incidence of hepatitis B, C, and D, as the leading factors in the development of hepatocellular carcinoma. Aim: to give a clinical and epidemiological characterization of hepatocellular carcinoma in the Republic of Sakha (Yakutia) at the initial stage of the program for the elimination of viral hepatitis for subsequent analysis of its effectiveness. Materials & Methods. A clinical and epidemiological analysis of morbidity, mortality, cumulative survival in hepatocellular carcinoma in the Republic of Sakha (Yakutia) over a 10-year period (2009-2018) was carried out. Predictors for the development of hepatocellular carcinoma were analyzed based on primary medical records and a survey of 125 patients. Results and discussion. The incidence rate of hepatocellular carcinoma in the Republic of Sakha (Yakutia) over the past 10 years is 2.0 3.9 times higher than the corresponding indicator in the Russian Federation. The highest mortality from the studied pathology is noted in the Central and Polar zones of the republic. According to the materials of the cancer registry, the median cumulative survival of patients with carcinoma was 13.7 months from the date of diagnosis, which is significantly higher than ten years ago. The main risk factors have been identified, among which the leading role is played by infection with hepatitis C, B, and D. viruses. Also, alcohol abuse, diabetes mellitus, overweight, and smoking are important. Conclusion. The Republic of Sakha (Yakutia) is a hyperendemic region of the Russian Federation in terms of the incidence of hepatocellular carcinoma with a predominance of the male population in its structure. The rate of decrease in the incidence of liver cancer in the country will depend on the effectiveness of the regional program for the elimination of viral hepatitis and the decrease in the incidence of cirrhosis of the liver of non-infectious etiology.
Present comparative epidemiologic characteristics of viral hepatitis C in Mongolia and Irkutsk Region taking into account racial origin of the studied populations.
The studies were carried out in ...2009-014 on the territory of Irkutsk Region in Mongolia. Prevalence of viral hepatitis based on serological monitoring, virus RNA detection, risk factors, change in structure of circulating genotypes, hepatocellular carcinoma morbidity were studied.
Epidemiologic manifestations of viral hepatitis C in Mongolia, in contrast to Irkutsk Region, are characterized by, a wider prevalence of the disease, predominance of the fraction of seropositive individuals in age category of above 50 years and predominance of genotype 1 virus in circulation. In recent years an evolution of diversity of circulating' irus genotypes, ook place towards a reduction of the fraction of genotype in Mongolia and Russia due tor ni ncrease of the fraction of genotype-3. Expressed,differences in average-annual values of hepatocellular carcinoma morbidity were detected, that were more than 10 times higher among Mongoloids compared with Caucasians.
Pronounced differences were detected in manifestations of epidemic process of viral hepatitis C in Mongolia and Asian part of Russia, represented by Eastern Siberia, that are associated with ethnic, social and, cultural living conditions of the indigenous population.
Aim. The current study is aimed at determining differences of epidemiological and clinical profiles associated with HCC in patients belonging to ethnic groups of Asians from Mongolia and Caucasians ...from Asian region of Russia. Materials and methods. The studies were carried out in the cross-border regions of Mongolia and Asian part of Russia (Irkutsk region). 300 patients with hepatocellular carcinoma (HCC) of the Caucasian and Mongolian races were enrolled in the study. The level of alpha-fetoprotein (AFP) in the serum was determined by the chemiluminescence technique. Results. The long-term dynamics of the HCC incidence shows more unfavourable trends in the territory of Mongolia compared to Irkutsk region. In both groups, male patients over 60 years of age predominated. Patients from Mongolia often have a history of jaundice and alcohol abuse. Out of the etiological factors, HCC is more often associated with the hepatitis B virus in Mongolia than in the Asian part of Russia. At the same time, in Caucasians, HCC develops primarily on the background of liver cirrhosis. In patients with HCC, AFP level higher than 20 ng / ml were significantly more frequent in the ethnic group of Caucasoids than in Mongoloids. Conclusions. Mongolia in terms of the incidence of HCC belongs to the hyperendemic regions of the world. In this country, among the risk factors for the development of the disease, hepatitis B virus plays a major role, which significantly differs from the Asian part of Russia. For the purpose of early diagnosis of HCC, it is necessary to search for new molecular markers or their combinations due to the insufficient diagnostic efficiency of AFP determination.
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