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The aim of the study was to identify the most effective serum tumor markers for early diagnosis of hepatocellular carcinoma based on the combination of diagnostic characteristics and correlations., Materials and Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Conflict of interest. The authors have no conflicts of interest to declare.

Liver cirrhosis in the outcome of hepatitis C is the leading cause of hepatocellular carcinoma (HCC) in the world. Early diagnosis and timely treatment of HCC are important for reducing mortality and increasing life expectancy of patients with hepatocellular carcinoma. To assess the risk of HCC, the definition of alpha-fetoprotein (AFP) in the blood is most widely used, but low sensitivity limits its diagnostic value. In 2012, a new HCC biomarker - osteopontin (OPN), which is a secreted phosphoprotein that has a high affinity for integrins was proposed. The level of acute renal failure begins to rise in the early stages of malignancy, before the period of HCC detection by imaging methods, and has significantly better sensitivity than AFP. The purpose of this study is to evaluate the diagnostic efficacy of the combined determination of alpha-fetoprotein and osteopontin in prospective monitoring of patients with chronic hepatitis C in the advanced phase of liver fibrosis. Monitoring of 588 patients with hepatitis C was carried out from February 2013 to February 2019. HCC was detected in 55 of them (2.6% per year). The combination of 2 biomarkers showed better diagnostic efficacy than alpha-fetoprotein and osteopontin separately: AUC 0.85 (95% CI 0.80-0.90) versus AUC 0.63 (95% CI 0.57-0, 70) and AUC 0.82 (95% CI 0.77-0.88), respectively. This combination showed a sensitivity of 85.5% and made it possible to diagnose HCC with a prognostic level of a positive result of 72.3% at 19,4±0,8 weeks before the diagnosis was confirmed by instrumental imaging methods (ultrasound, MRI, CT). In the combined variant, ARF made the greatest contribution to the increase in diagnostic efficacy (AUC). At an early and very early stage of HCC development, isolated HCC elevations were found in only 5.4% of patients. Conclusion: the combined use of alphafetoprotein and osteopontin as a diagnostic panel can be recommended for monitoring patients with liver cirrhosis in the outcome of hepatitis C and predicting HCC at an early stage of development., Competing Interests: The authors declare no conflict of interest.

The study was aimed at identifying prognostic factors of antiretroviral therapy (ARVT) in patients with HIV infection at different stages of the disease and developing an algorithm for the three-component assessment of compliance with therapy. A total of 280 patients given ARVT for at least 6 months were available for comprehensive examination, questionnaire study for the detection of non-compliance risk factors, and psychological testing with the evaluation of non-compliance from the anxiety level (Sheehan scale) with the use of cluster analysis. The study revealed the most significant criteria for the assessment of compliance with therapy and non-compliance risk factors associated with ARVT conditions.

Aim: To determine the correlation between interleukin 28B (IL28B) gene polymorphism in patients with chronic hepatitis C (CHC), the presence or absence a rapid virologic response to antiviral therapy, and a number of immunological characteristics as a basis for a personalized approach to treating the patients., Subjects and Methods: Seventeen CHC patients infected with hepatitis C virus genotype 1b were examined and underwent genetic testing for IL28B gene polymorphism for rs12979860 (CC, CT or TT genotypes) and rs8099917 (TT, TG or GG genotypes) using the modified method of adjacent samples, which revealed single nucleotide substitutions in the genes. Their immunological parameters were identified by a flow cytometry technique by taking into account whether a rapid virologic response had been achieved., Results: The key phenomena of a rapid virologic response in the representatives of different IL28B genotypes are the nonspecific proliferative activity of blood natural killer cells before treatment, as well as the count of regulatory T cells before and 4 weeks after therapy start., Conclusion: To predict the efficiency of antiviral therapy for CHC, it is desirable to supplement genetic studies with immunological data.

Aim: To evaluate the clinical and morphological variants of kidney abnormalities in HIV-infected patients., Subjects and Methods: Thirty HIV-infected patients (60% men and 40% women) aged 26 to 54 years (mean age 31.6 +/- 4.7 years) who had undergone diagnostic needle renal biopsy were examined. The indication for the biopsy was nephrotic syndrome (NS) (isolated or concurrent acute nephritic syndrome) and/or decreased renal function. The morphological study of biopsy specimens included light microscopy and immunofluorescence assay., Results: In the examined HIV-infected patients, the histological variants of kidney abnormalities presented with immune complex glomerulonephritis (ICGN) in 26 cases and with focal segmental glomerulosclerosis (FSGS) in 4 cases. The clinical manifestations of ICGN were as follows: NS (61.5%), acute nephritic syndrome (in more than one third of the patients) concurrent with hematuria, as well as mainly grades 2-3 arterial hypertension (AH) (12/14) and renal dysfunction. Immune complex glomerulopathies were marked by polymorphism in the renal morphological pattern with fluorescence during immunofluorescence microscopy in most cases of virtually all classes of immunoglobulins (IgA, IgM, IgG) and complement system fragments (C3, C1q). FSGS was clinically characterized by NS concurrent with AH, hematuria. The morphological subtypes of FSGS were exhibited by apical, perihilar, and nonspecific variants in 1, 1, and 2 cases, respectively. By the time the signs of renal dysfunction appeared, the HIV-infected patients with glomerulopathy were found to have a high viral load (HIV RNA >100 000 copies/ml) and low CD4 lymphocyte levels (< or = 200 in 1 microl)., Conclusion: In our study, the morphological pattern of chronic glomerulonephritis showed a preponderance of immune complex nephropathies with the clinical manifestations of acute nephritic syndrome and/or NS concurrent with hematuria. High viremia and depressed immune system may be risk factors for nephropathy.