Aim.To determine the role of the relationship of immunological disorders with interleukin-6 gene polymorphism in the formation of HCV-associated mixed cryoglobulinemia.Materials and methods. The study included 149 patients with chronic hepatitis C. The polymorphism of the IL-6 gene (rs1800795) was determined by the method of polymerase chain reaction, the quantitative content of IL-6, RF IgM and IgG by enzyme immunoassay, cryoglobulins by spectrophotometric method. The patients were divided into groups depending on the polymorphism of the IL-6 gene and the presence of mixed cryoglobulinemia.Results. The frequency of formation of HCV-associated mixed cryoglobulinemia depended on the polymorphism of the IL-6 gene. In patients with chronic hepatitis C with mixed cryoglobulinemia, the frequency of registration of the CC genotype of the IL-6 gene was lower than in patients without mixed cryoglobulinemia, namely, in 9.7 % versus 28.6 % of patients. The presence of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, was more often detected in patients with mixed cryoglobulinemia, namely, in 90.3 % of patients against 71.4 % of patients without signs of mixed cryoglobulinemia (χ 2 = 8.94, P = 0.003).In the presence of G-allele, the quantitative content of IL-6 in the serum of the general group of patients with CHC was higher than in healthy people (P < 0.01), and in the presence of the genotype, the CC did not differ from the control group (P > 0.05). The highest levels of IL-6 were recorded in patients with HCV-associated mixed cryoglobulinemia who had the G-allele. The content of IL-6 in the blood serum of these patients exceeded the indicators of both healthy people (P < 0.001) and the results of patients without mixed cryoglobulinemia (P < 0.01). In patients with chronic hepatitis C with mixed cryoglobulinemia, even in the presence of the CC genotype, the content of IL-6 in serum was higher both in comparison with healthy (P < 0.01) and in comparison with patients without signs of this extrahepatic manifestation (P < 0.01).In patients with chronic hepatitis C with mixed cryoglobulinemia, the presence of CG/GG genotypes was associated not only with the highest serum IL-6 content, but also with the presence of more pronounced autoimmune disorders due to a higher content of RF IgM (P = 0.04) and mixed cryoglobulins (P = 0.03) in serum, in comparison with patients who had the CC genotype. Moreover, the presence of more pronounced immune disorders in patients with HCV-associated mixed cryoglobulinemia in the presence of CG/GG genotypes was accompanied by more frequent manifestation of severe general weakness (P = 0.003), arthralgia (P = 0.02) and the formation of Meltzer's triad. Conclusion.The frequency of detection of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, is the highest in patients with HCV-associated mixed cryoglobulinemia (90.3 %). The presence of CG/GG genotypes in patients with chronic hepatitis C with mixed cryoglobulinemia contributes to more pronounced immunol...
The aim of the work – to present a case of positive use of tocilizumab in the treatment of pregnant woman with severe COVID-19. Materials and methods. A self-observation clinical case of severe coronavirus disease (COVID-19) in pregnant K., 40 years old, who was treated at Municipal Non-Profit Enterprise “Regional Infectious Diseases Clinical Hospital” of Zaporizhzhia Regional Council. The patient was treated in accordance with the “Protocol for the provision of medical care for the treatment of coronavirus disease (COVID-19)”. Results. Our own clinical observation demonstrates the formation of severe COVID-19 in a 40-year-old pregnant woman in the second trimester of pregnancy. Combination treatment with glucocorticoids in the presence of oxygen dependence on the 11th day of the disease was ineffective for two days of clinical and laboratory parameters monitoring, which required a decision on the additional appointment of tocilizumab. The development of “cytokine storm” clinical and laboratory signs on the 12th day of the disease was evidenced by the preservation of fever in the range of 37.5–37.8 °C, no regression of oxygen dependence. According to laboratory data, an increase in the severity of lymphopenia as a relative quantity – up to 5 % and absolute quantity – up to 0.5 × 109/l, an increase in fibrinogen – up to 5.8 g/l and D-dimer – up to 1.9 ng/ml, high level of C-reactive protein – up to 190 mg/l. These data justify the additional use of tocilizumab, which was administered at a dose of 8 mg/kg in the absence of contraindications. Tocilizumab administration was effective, contributing to oxygen dependence regression and recovery of laboratory parameters within a week. Conclusions. Our own clinical observation demonstrates the formation of severe COVID-19 in pregnant woman in the second trimester of pregnancy. Due to the ineffectiveness of glucocorticosteroid therapy and the presence of clear clinical and laboratory signs of “cytokine storm” on the 12th day of the disease, the use of tocilizumab was effective, which contributed to the oxygen dependence regression and recovery of laboratory parameters within a week. Treatment of pregnant woman with severe COVID-19 requires adherence to existing protocols.
Наведені сучасні дані про мікст-інфекцію, спричинену SARS-CoV-2 та вірусом грипу на різних етапах пандемії COVID-19. Початок пандемії COVID-19 збігся із сезонним ростом захворюваності на грип, що призводило до мікст-інфікування та підвищувало ризик летального висліду. Незважаючи на обмеженість ресурсів до тестування на інші респіраторні інфекції під час пандемії COVID-19, представлені в літературі дані свідчать про суттєві зміни перебігу мікст-інфікування, залежно від циркуляції домінуючого штаму SARS-CoV-2. Так, під час домінування штаму Омікрон SARS-CoV-2 збільшується кількість випадків грипу та, відповідно, мікст-інфікування. Частота мікст-інфекції COVID-19 та грип не висока, проте в цих випадках характерні яскравіша клінічна симптоматика та вищий ризик тяжчого ступеня хвороби, що потребує своєчасного тестування на обидві ці інфекції для вибору оптимального противірусного лікування. Вивчення особливостей формування «цитокінового шторму» є перспективним напрямком дослідження для подальшої розробки диференційних засобів імунотропного лікування. Профілактичні заходи повинні включати вакцинацію як проти COVID-19, так і проти грипу в умовах триваючої пандемії COVID-19 та з урахуванням сезонного грипу.
Aim. The aim of the work was to determine the influence of interleukin-6 gene polymorphism on the effectiveness of antiviral therapy in patients with chronic hepatitis C. Materials and methods. A total of 83 patients with chronic hepatitis C (CHC). were included in the study. The efficacy of therapy with the peg-IFNα + SOF + RBV was analyzed depending on the polymorphism of interleukin-6 gene (rs1800795). Results. All CHC patients with the CC genotype (14-100 %) responded to antiviral therapy with the peg-IFNα + RBV + SOF, but only 85.5 % of the patients with CG/GG genotypes responded (59 of the 69). In CHC patients with CG/GG genotypes, who responded to the therapy by SVR 24 formation, the HCV-RNA negativization was slower, in contrast to patients with the CC genotype, who showed a persistent absence of the virus in the blood from the 4th week of treatment. All patients with the CC genotype of IL-6 gene polymorphism presented complete normalization of ALT activity at this time if SVR 24 had been achieved. In the vast majority of CHC patients with SVR 24 and the CG/GG genotype after the therapy cessation, ALT activity continued to decrease and normalized after 24 weeks of observation in 94.9 % (56 of the 59). However, 20.0 % of patients with the CG/GG genotype who did not respond with the formation of SVR 24, had elevated serum ALT activity at the time of SVR 24 evaluation. Kendall's rank correlation was performed to determine the factors, which statistically significantly affect the results of peg-IFNα + RBV + SOF therapy. IL-6 gene polymorphism had an effect on the efficacy of therapy, both on the HCV-RNA negativization in the blood at the end of treatment (P = 0.04) and on the achievement of SVR 24 (P = 0.03). The lack of response as well as the lack of SVR 12 and SVR 24 formation at the time of therapy completion were associated with the IL-6 gene CG/GG polymorphism presence and a higher index of ALT activity at the beginning of treatment (τ =-0,18, P < 0.01). Conclusions. In CHC patients, the CC genotype of IL-6 gene (rs1800795) is a favorable prognostic factor for the formation of SVR 24 in the treatment of peg-IFNα + RBV + SOF. Patients who did not respond to the treatment by SVR 24 formation had only the IL-6 gene CG/GG polymorphism. Even in HCV patients with CG/GG genotypes who responded to the treatment by SVR 24 formation, the negativization of HCV-RNA in the blood was slower, unlike the patients with CC genotype. The absence of response at the time of therapy completion, as well as the absence of SVR 12 and SVR 24, were associated with the presence of the IL-6 gene CG/GG polymorphism and a higher level of ALT activity at the beginning of therapy (τ =-0,18, P < 0.01).
Kalashnyk K. V., Riabokon Yu. Yu. The role of interleukin-17 gene polymorphism (RS612242 C11139G) in the formation of the cryoglobulinemic syndrome in patients with chronic hepatitis C.
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