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The review presents the main data on the problem of cryoglobulinemic vasculitis associated with HCV infection. The options for the course are considered, and modern diagnostic criteria, the choice of tactics, and the effectiveness of various treatment regimens are presented. The use of modern antiviral drugs makes it possible to achieve the eradication of the virus in 95 % of patients. However, in some patients, clinical and immunologic markers of vasculitis persist despite viral clearance. The article discusses the concept that the persistence of B-cell clones after achieving a sustained virological response may underlie the pathogenesis of HCV-independent CV reactivation.

Сardiovascular disease (СVD) is the most common complication of chronic kidney disease (СKD). In patients with the earlier stages of CKD, the risk of death from CVD greatly exceeds the risk of progression to end-stage renal disease. In recent years, accumulated data suggest that chronic kidney disease — mineral and bone disorders (CKD-MBD) are strongly associated with cardiovascular events and mortality. Among cardiovascular damage in CKD, both, the progressive cardiac remodeling and vascular calcifi cation, contribute immensely, and lead to an urgently high cardiovascular mortality in patients with CKD. Clarifi cation of CKD progression mechanisms and possible early markers of CVD has led to interest in studying the identifi ed factors such as fi broblast growth factor-23 (FGF-23), Klotho and sclerostin in recent years. Results of studies show that disorders in the system of FGF-23–Klotho–sclerostin correlate with the frequency and severity of hypertension, cardiac remodeling, vascular calcifi cation, anaemia, malnutrition, infl ammation, and strongly aggravate cardiovascular risk in CKD. This review represents an analysis of the available data showing the potential association of СVD with established (phosphate, parathyroid hormone (PTH), Vitamin D) and newer (FGF-23, Klotho, sclerostin) СKD-MBD biomarkers. In addition, it has been shown that renoprotective therapy, including renin-angiotensin blockers, low-protein diet with amino/keto acid supplementation, phosphate binders, erythropoiesis stimulators, vitamin D metabolites used to reach the target levels of blood pressure, serum phosphorus, haemoglobin, PTH and nutritional status disorders, can aff ect CKD-MBD biomarkers and reduce the risk of cardiovascular events in CKD patients.

Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90-95% of cases.Ровно 30 лет назад был идентифицирован вирус гепатита С. За эти годы достигнут огромный успех в лечении гепатита С, который в настоящее время рассматривается как практически полностью излечимое заболевание. В обзоре представлены основные этапы становления противовирусной терапии гепатита С, эффективность различных схем лечения. Наибольший прогресс в лечении отмечен в течение последних 5 лет, когда появились и стали широко применяться, в том числе и в России, препараты с прямым противовирусным действием, которые обеспечивают элиминацию вируса в 90-95% случаев.

It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD).The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)).The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p.Установлено, что повышение уровня фактора роста фибробластов (FGF-23) в сыворотке крови больных хронической болезнью почек (ХБП) вносит существенный вклад в ремоделирование сердца и сосудов. Точные механизмы влияния избыточного уровня FGF-23 на миокард в настоящее время активно изучаются. В то же время полагают, что эффекты FGF-23 на сердце могут быть обусловлены нарастающим дефицитом белка Klotho по мере прогрессирования ХБП. Параллельно этим изменениям ряд работ указывает на персистирование умеренно повышенных уровней тропонинов в сыворотке крови больных ХБП даже при отсутствии у них клинических проявлений кардиоваскулярных заболеваний (КВЗ). Цель исследования. Установить/опровергнуть наличие причинно - следственной связи между повышенным уровнем FGF-23, сниженным уровнем Klotho и повышенным уровнем тропонина-I (Tr-I) как наиболее специфического тропонина при ХБП. Материалы и методы. В исследование включено 130 пациентов с ХБП стадий 1-5D без клинически выраженных симптомов КВЗ (ИБС II-IV ФК, ХСН II-IV класса по NYHA, миокардит, перикардит, аритмии), а также тяжелой артериальной гипертензии (АГ; артериальное давление160/90 мм рт. ст.) по данным лабораторных и инструментальных методов обследования. У отобранной группы больных изучены: сывороточные уровни FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies), Tr-I (high-sensitive assay), а также данные инструментальных методов обследования: электрокардиографии, эхокардиографии [индекс массы миокарда левого желудочка (ИММЛЖ), степень кальцификации структур сердца (СКС) - с помощью полуколичественной балльной шкалы], сфигмографии [индексы аугментации (жесткости) сосудов, скорость пульсовой волны (СПВ), центральное (аортальное) давление (ЦАД), кровоснабжение субэндокарда (КСЭ) - с помощью прибора Shygmacor (Австралия)]. Результаты и обсуждение. Изменение сывороточных уровней FGF-23, Klotho и Tr-I зависит от стадии ХБП. Выявлены следующие корреляции: FGF-23 - с Tr-I (r=0,601; p.

Protein restriction diet (PRD) with ketoanalagues of essential amino acids (KA) combination can improve of chronic kidney disease (CKD) course while, the precise mechanisms of PRD + KAA action in CKD are not known yet. We have conducted a prospective, randomized, controlled study of PRD and KAA patient's group in compare with PRD without KAA group in regarding to serum Klotho and FGF-23 levels in patients with CKD.The study included 79 CKD 3b-4 stages patients, non - diabetic etiology, used PRD (0.6 g/kg/day). The patients were randomized in two groups: 42 patients, received PRD + KAA (Group 1) and 37 patients continued the PRD without KAA (Group 2). Serum FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule, Merk Millipore MILLENZFGF-23-32K), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies, IBL-Takara 27998-96Well) levels, as well as instrumental examination: bioimpedance analysis [assess of muscle body mass (MBM), fat body mass (FBM), body mass index (BMI) and others]; sphygmography [assess of augmentation (stiffness) indices (AI), central (aortal) blood pressure (CBP) by «Sphygmacor» device]; as well as echocardiography [assess of cardiac (valvular) calcification score (CCS) and left ventricular myocardium mass index (LVMMI)], were studded in addition to conventional examination.To the end of 14th month of the study the PRD group reached a body mass index (BMI) decrease (p=0.046), including MBM in men (p=0.027) and woman (p=0.044). In addition, higher FGF-23 (p=0.029), and lower Klotho (p=0.037) serum levels were revealed in the PRD group compared to the PRD+KAA group as well as the increase in AI (p=0.034), CCS (p=0.048), and LVMMI (p=0.023).Use of PRD + KAA provides adequate nutrition status and more efficient correction of FGF-23 and Klotho imbalance in CKD progression that may contribute to alleviation of both cardiovascular calcification and cardiac remodeling in CKD. Importantly, a prolonged PRD use without supplementation of KAA may lead to malnutrition signs.Малобелковая диета (МБД), дополненная кетоаналогами незаменимых аминокислот (КА), вносит вклад в улучшение течения хронической болезни почек (ХБП), однако точные механизмы действия МБД + КА пока не установлены. Мы провели проспективное рандомизированное контролируемое сравнительное исследование влияния МБД + КА и изолированной МБД (МБД без КА) на сывороточные уровни фактора роста фибробластов-23 (FGF-23) и белка Кlotho у больных ХБП. Материалы и методы. В исследование включены 79 больных ХБП 3b-4 стадии недиабетической этиологии, соблюдавшие МБД (0,6 г/кг массы тела в сутки). Пациенты рандомизированы в две группы: 42 пациента, получавшие МБД + КА (1-я группа), и 37 пациентов, продолживших МБД без добавления КА (2-я группа). В дополнение к стандартным методам обследования определяли сывороточный уровень FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule) и Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies), а также проводили биоимпедансометрию [оценка мышечной массы тела (ММТ), жировой массы тела (ЖМТ), индекса массы тела (ИМТ) и др.]; сфигмографию [определение центрального (аортального) артериального давления (ЦАД) - систолического и диастолического, индекса аугментации (жесткости) сосудов (ИА) - с помощью аппарата SphygmаCor]; эхокардиографию [оценка степени кальцификации структур сердца (СКС) и индекса массы миокарда левого желудочка (ИММЛЖ)]. Результаты и обсуждение. К концу 14-го месяца наблюдения группа МБД достигла статистически значимого снижения ИМТ (p=0,046), включая ММТ у мужчин (p=0,027) и женщин (p=0,044). Кроме того, в группе МБД в этот момент выявлены более высокий средний уровень FGF-23 (p=0,029) и более низкий уровень Klotho (p=0,037), чем в группе МБД + КА. Повышение ИА (p=0,034), СКС (p=0,048) и ИММЛЖ (p=0,023) также отмечалось более часто в группе МБД без КА на момент окончания исследования (14-й месяц наблюдения принят за момент окончания исследования). Заключение. Применение МБД в сочетании с КА обеспечивает поддержание адекватного нутритивного статуса и вносит вклад в более эффективную коррекцию нарушения соотношения FGF-23 и Klotho, что может способствовать снижению кардиоваскулярной кальцификации и замедлению ремоделирования миокарда при ХБП. В то же время длительное применение МБД без добавления КА может приводить к белково - энергетической недостаточности.

Hepatitis C virus (HCV) is a global population problem due to its high prevalence, usually late diagnosis, the difficulties of treatment. In the prognosis of patients with HCV not only hepatic, but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (CG), are important. Mixed CG is currently considered as a B-cell benign lymphoproliferative disorders. The role of HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin’s lymphoma (NHL). The purpose of the review was to provide an overview of recent literature data and the meta-analysis of epidemiological data explaining the role of HCV in the development of NHL. The review also discusses the treatment for HCV-associated NHL by antiviral therapy or other therapeutic options, such as chemotherapy.

Aim. To evaluate the results of immunosuppressive and/or antiviral treatment of patients with hepatitis C virus (HCV)-induced mixed cryoglobulinemic (MC) vasculitis. Material and methods. This prospective study included 60 patients (m/f - 23/49, age - 45,9±11,1) with HCV-MC vasculitis. The Birmingham vasculitis activity score (BVAS) was used before the treatment and during follow-up (3,5±4,1 years). The rate of clinical and immunological responses to the treatment, the frequency of relapses and the influence of different treatment approaches on the prognosis of the disease were evaluated. Logistic regression analysis was used to assess factors influencing the effectiveness of treatment. Results. 23 (38%) patients had liver cirrhosis. BVAS scores before treatment ranged from 2 to 36. 25 (41,6%) patients had BVAS≥15. 6 (10%) patients presented with B-cell non-Hodgkin lymphomas. The antiviral treatment resulted in the elimination of the virus in 48.0% of the cases, complete clinical and immunological responses were achieved in 68,0% and 32,0% respectively. It had an advantage over immunosuppressive therapy in terms of long-term results of the treatment. We established the superiority of anti-CD monoclonal antibodies (rituximab) over conventional immunosuppressive drugs: complete clinical response 73% vs 13% (p=0,001). Combined therapy (rituximab and antiviral treatment) was more effective in patients with severe vasculitis (BVAS≥15). A case of successful treatment using direct-acting antivirals (DAAs) is reported. Causes of MC-vasculitis relapses after achieving sustained viral response are discussed. Conclusion. Antiviral therapy is the treatment of choice in all patients with HCV- HCV-MC vasculitis. Preference should be given to highly effective and safe modern therapy regimens with the use of DAAs. The antiviral treatment of severe forms of vasculitis must be combined with rituximab therapy.

Aim of the study was to explore the role of the FGF-23/sKlotho/sclerostin ratio disturbance in the determining of cardiovascular risk in end stage renal disease (ESRD) patients, receiving treatment with regular hemodialysis (НD) or hemodiafiltration (НDF) online in Russia.42 patients with ESRD, at the age of 18-55 years, treated with HD or HDF on line for at least 6 months, were examined. 22 (52.3%) patients received traditional HD, the remaining 20 (47.7%) - HDF online. In all the patients, in addition to a general examination, the serum levels of FGF-23, sKlotho, sclerostine (by ELISA), their associations with cardiovascular risk factors (left ventricular hypertrophy (LVH), acute coronary syndrome (ACS), serum troponin I levels) with the numbers of techniques (ECG; Eho-CGF (with calculation of left ventricular myocardium mass index (LVMMI), as well as the relative thickness of the walls of the left ventricle (RWT); sphygmography (central (aortal) blood pressure (CBP), subendocardial blood flow (SBF) - by «Sphygmocor»), and the effect of regular HD and HDF on serum levels of the studied markers, were assessed.An independent effect of FGF-23 on the risk of LVH, as well as on the increase of serum troponin I in the studied ESRD patients [β=3.576 plt;0.01, and β=1.115, plt;0.05, respectively] was found. Serum Klotho was the factor most associated with the CBP [β=-0.023; plt;0.001]. The increased serum sclerostin was correlated with a lower incidence of both reduced SBF [r=0.492; plt;0.05], symptoms of coronary heart disease [r=-0.449; plt;0.05] and rhythm disturbances [r=-0.446; plt;0.05]. In addition, in HD patients higher FGF-23 and lower Klotho and sclerostine serum levels were associated with: inadequate dialysis syndrome (Kt/Vlt;1.1; r=0.463; plt;0.05), chronic inflammation (C-reactive proteingt;10 mg/L; r=0.612; plt;0.01), and with a decrease in serum albumin level (lt;35 g/l; r=0.459; plt;0.05). The FGF-23/sKlotho/sclerostin ratio disturbance was more pronounced in patients treated with traditional HD then HDF online. A direct correlation (r=0.445; plt;0.05) was established between FGF-23 serum levels and serum phosphorus, which was more pronounced in HD patients (r=0.545; plt;0.01).In HD and HDF ESRD patients, higher serum FGF-23 and lower sKlotho and sclerostin levels were associated with a chronic inflammation, malnutrition, secondary hyperparathyroidism, and may considered as predictors of cardiovascular complications such as LVH, ACS, rhythm disturbances, persisting of subincreased serum troponin I.

The study demonstrated the results of the comparative analysis of various types of renal replacement therapy effects on the quality of life patients with terminal stage of chronic kidney disease on the basis of standardized questionnaires. It has been shown that the quality of life is significantly improved after a kidney transplantation. At the same time, it has also been found that the introduction of home dialysis, epoetins, active metabolites of vitamin D, calcimimetics in the clinic care expanded the opportunities for the labor rehabilitation of the dialysis patients and made their quality of life comparable with the same of the kidney transplant recipients.

To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV).Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out.24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91).HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.Цель исследования. Обобщить опыт многопрофильного терапевтического стационара в лечении больных криоглобулинемическим васкулитом (КВ), ассоциированным с вирусом гепатита С (HСV). Материалы и методы. Обследовали и наблюдали в среднем 2,8±3,6 года 72 больных хроническим гепатитом С (ХГС) с ассоциированным с HСV КВ (средний возраст 49,4±10,3 года). Эффективность традиционной (глюкокортикостероиды ± циклофосфамид) и селективной (ритуксимаб) иммуносупрессивной терапии (ИСТ) оценена в 31 и 15 наблюдениях соответственно, противовирусной терапии (ПВТ) - в 25. Активность васкулита оценивали с помощью BVAS (Birmingham vasculitis activity score). Изучали выживаемость больных, проводили многофакторный логистический регрессионный анализ. Результаты. У 24 (33,4%) из 72 больных имелась стадия цирроза печени (ЦП). Средняя оценка по BVAS до лечения составила 11,9±7,2 балла (от 2 до 36 баллов). Тяжелая форма КВ (BVAS ≥15 баллов) имелась у 30,6% больных. ПВТ сопровождалась достижением устойчивого вирусологического ответа у 48%, клинической ремиссии - у 68% больных и имела преимущество перед ИСТ в отношении отдаленных результатов лечения. Ритуксимаб оказался статистически значимо эффективнее традиционных иммуносупрессоров (ремиссия 73 и 13% соответственно). У больных с тяжелыми формами васкулита наиболее эффективна сочетанная терапия (ритуксимаб и ПВТ). Умерли 16 больных: от осложнений васкулита 37,5%, инфекции 37,5%, осложнений ЦП 25%. Факторами, негативно влияющими на прогноз, явились возраст55 лет (отношение шансов - ОШ 4,49), наличие ЦП (ОШ 3,68), почечной недостаточности (ОШ 4,66) и применение глюкокортикостероидов (ОШ 3,91). Заключение. КВ, ассоциированный с HСV, может определять прогноз хронической инфекции HСV. ПВТ является терапией выбора у всех больных HСV КВ. У больных с тяжелыми формами васкулита ПВТ должна сочетаться с терапией ритуксимабом.