Cryoglobulinemia and hepatitis C virus

The review presents recent data on cryoglobulinemiaassociated with a hepatitis C virus: prevalence, pathogenesis, clinical manifestations, laboratory diagnostics, approaches to therapy

PHARMACOECONOMIC ASSESSMENT OF USING INTERFERON-FREE REGIMENS FOR CHRONIC HEPATITIS C AFTER LIVER TRANSPLANTATION

This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3

КРИОГЛОБУЛИНЕМИЯ И ВИРУС ГЕПАТИТА С

The review presents recent data on cryoglobulinemiaassociated with a hepatitis C virus: prevalence, pathogenesis, clinical manifestations, laboratory diagnostics, approaches to therapy.В обзоре представлены последние данные о криоглобулинемии, ассоциированной с вирусом гепатита С: частота встречаемости, патогенез, клинические проявления, лабораторная диагностика, подходы к терапии

ФАРМАКОЭКОНОМИЧЕСКОЕ ОБОСНОВАНИЕ ИСПОЛЬЗОВАНИЯ БЕЗИНТЕРФЕРОНОВЫХ ТЕРАПЕВТИЧЕСКИХ СХЕМ ПРИ ХРОНИЧЕСКОМ ГЕПАТИТЕ С ПОСЛЕ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ

This article contains analysis of current combination treatment regimens for chronic hepatitis C after liver transplantation. Antiviral therapy with long-acting interferons and ribavirin is of low efficiency and high costs. The clinical and economic benefits of interferon-free treatment regimen for patients infected with genotype 1 HCV using dasabuvir, paritaprevir boosted with ritonavir, ombitasvir (Viekira Pak) and ribavirin have been shown. Registration and introduction into clinical practice of new direct-acting antiviral drugs will significantly expand the arsenal of tools for the treatment of recurrent HCV infections, in particular in patients infected with hepatitis C virus genotypes 2 and 3. В статье проведен анализ существующих схем комбинированной противовирусной терапии хронического гепатита С после трансплантации печени. Проведение противовирусной терапии с использованием пролонгированных интерферонов и рибавирина низкоэффективно и высокозатратно. Доказано клиническое и экономическое преимущество безинтерферонового режима лечения пациентов, инфицированных вирусом гепатита С 1-го генотипа, с использованием дасабувира, паритапревира, бустированного ритонавиром, омбитасвира (Викейра Пак) и рибавирина. Регистрация и внедрение в клиническую практику новых препаратов прямого противовирусного действия позволит существенно расширить арсенал средств для лечения возвратной HCV-инфекции, в том числе у пациентов, инфицированным вирусом гепатита С 2-го и 3-го генотипа

Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%

Clinical and immunological characteristics of patients with chronic hepatitis C during antiviral therapy in interferon-free regimen

Aim. To study the biomarkers of liver inflammation that occur during antiviral therapy in the interferon-free regimen. Methods. 14 patients were examined during antiviral therapy of chronic viral hepatitis C genotype 1. Treatment with dasabuvir, ombitasvir, paritaprevir and ritonavir for 12 weeks was received by 8 patients. Daklatasvir and asunaprevir was administered to 6 patients for 24 weeks. 11 patients had the concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) measured in the blood plasma by multiplex analysis. In six patients, the content of CXCR3+ and CCR6+ receptors in different subpopulations of lymphocytes was determined by flow cytofluorimetry. Patients were divided into 2 groups: without liver fibrosis and with severe fibrosis. Results. 100% demonstrated virologic response. In both groups, significant reduction of CXCL10/IP-10 concentration was found in the patients at the end of treatment compared to pre-therapy (p=0.025 and 0.00015, respectively). In the first group a tendency to increase of the relative content of T-lymphocytes (p=0.065) was observed, and in the second group, a significant increase of the relative content of TNKCCR6+ (p=0.02) was observed. Conclusion. Chemokine CXCL10/IP-10 is a biomarker characterizing the decrease of liver inflammation during therapy and not depending on the degree of liver fibrosis. The tendency to increase of the relative content of T lymphocytes in the first group and a significant increase in TNKCCR6+ cells during treatment in the second group may play an important role in eliminating hepatitis C virus

ЭПИДЕМИОЛОГИЧЕСКИЕ ОСОБЕННОСТИ И ЭВОЛЮЦИЯ КЛИНИКИ БРЮШНОГО ТИФА В САНКТ-ПЕТЕРБУРГЕ

Purpose: To study an epidemiological features and evolution of clinical presentation of typhoid fever in modern megapolis Materials and methods: A study of 115 patient’s medical records was performed. All patients were hospitalized in Clinical Infectious Diseases Hospital named after S.P. Botkin, Saint-Petersburg, Russia during 2005–2017 with confirmed diag№sis of typhoid fever. We have conducted a comparison of epidemiological and clinical features between 59 patients hospitalized in 2005–2009 and 56 hospitalized in 2010–2017. Results: There was increase proportion of Central Asia’ countries citizens among study group during recent years. Social status of affected patients had also changed recently due to decrease fraction of homeless people along with decreased number of patients with accompanied infectious diseases. Atypical clinical presentation had become more common №wadays with most of a patients presented with moderate severity form of disease. Conclusion: Clinical presentation and epidemiology of typhoid fever are prone to changes over time. New data on epidemiology and predominance of atypical form of disease need to be considered to ensure prompt diag№sis of a disease.Цель: изучить особенности эпидемиологии и клинического течения брюшного тифа в современном мегаполисе.Материалы и методы: В исследование включено 115 пациентов с брюшным тифом, госпитализированных в Клиническую инфекционную больницу им. С.П. Боткина в 2005–2017 гг. Проведено сравнение особенностей эпидемиологии и клинического течения брюшного тифа в крупном мегаполисе у 59 пациентов, госпитализированных с 2005 по 2009 г., и 56 пациентов, госпитализирован-ых с 2010 по 2017 г.Результаты: в последние годы среди пациентов с брюшным тифом выявлено увеличение доли граждан Средней Азии. Нами наблюдалось изменение социального статуса больных за счет уменьшения доли лиц без определенного места жительства, а также уменьшения числа пациентов с сопутствующей инфекционной патологией. В клинической картине заболевания стали преобладать атипичные формы со среднетяжелым течением.Заключение: клиническая картина и эпидемиология брюшного тифа подвержены динамическим изменениям. Новые данные об эпидемиологии брюшного тифа и его преимущественно атипичном течении необходимо учитывать для своевременной диагностики заболевания

ЛЕТАЛЬНЫЕ ИСХОДЫ ПРИ ГРИППЕ: КЛИНИКО-МОРФОЛОГИЧЕСКИЙ ПОДХОД К НЕПОСРЕДСТВЕННЫМ ПРИЧИНАМ СМЕРТИ

Influenza is one of the most outspread infections not seldom leading to lethal outcomes. Immediate death causes are analyzed rarely. Material and methods. We provided clinic-pathological correlations in 23 cases with lethal outcomes in 1999, 15 – in 2009, 31 in 2016 and 10 in 2017. Results. It was shown that in 2009 and 2017 most frequent lethal outcomes were related to bacterial superinfection in elderly people with severe background pathology. In 2009 and 2016 the leading role played respiratory distress syndrome predominantly in people of middle age, frequently with obesity. Conclusions: by circulation of different strains of influenza A virus the disease has substantial peculiarities. Lethal outcomes may be related: 1) severe respiratory insufficiency due to respiratory distress syndrome; 2) generalized viral infection; 3) secondary bacterial pneumonia; 4) aggravation of severe somatic diseases. Many aspects of pathogenesis need complex.study.Грипп является одной из самых распространенных инфекций, приводящих к нередким летальным исходам. Непосредственные причины смерти при гриппе анализируются редко.Материал и методы: проведены клинико-морфологические сопоставления в 23 наблюдениях с летальным исходом взрослых в 1999 г., 15 – в 2009 г., 31 – в 2016 г. и 10 – в 2017 г.Результаты: показано, что в 2009 и 2017 гг. наиболее часто летальные исходы были связаны с бактериальной суперинфекцией, как правило, у пожилых людей с тяжелой фоновой патологией. В 2009 и 2016 гг. ведущую роль играл респираторный дисстресс-синдром преимущественно у лиц среднего возраста, чаще с ожирением.Выводы: при циркуляции разных штаммов вируса гриппа типа А заболевание имеет существенные особенности. Летальные исходы могут быть связаны с: 1) тяжелой дыхательной недостаточностью при респираторном дисстресс-синдроме; 2) генерализованной вирусной инфекцией; 3) вторичной бактериальной пневмонией; 4) обострением тяжелых соматических заболеваний. Многие аспекты патогенеза нуждаются в комплексном изучении.

ЭПИДЕМИОЛОГИЧЕСКИЕ И КЛИНИКО-ЛАБОРАТОРНЫЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ЗАВОЗНЫХ СЛУЧАЕВ МАЛЯРИИ НА ТЕРРИТОРИИ СЕВЕРО-ЗАПАДНОГО ФЕДЕРАЛЬНОГО ОКРУГА

Purpose: analysis of epidemiological, clinical and laboratory features of imported malaria in the North-Western Federal district (NWFD) in 2012–2016. Research materials: the study included 84 patients treated for malaria in the hospitals of the NWFD. Results: 84 cases of malaria were registered in the NWFD from 2012 to 2016, which constituted 18,9% of all cases registered inRussian Federation(n=445):St. Petersburg(n=60),Arkhangelsk(n=10),Murmansk(n=5),Leningradregion (n=4),Vologdaregion (n=2) and 1 case in Komi,NovgorodandKaliningradregion. Patients with malaria had a history of a recent visit to: Asian countries (37%, n=31), West Africa (35%, n=30), North Africa (11%, n=7),South Africa(8%, n=7), East and Central Africa (3% correspondingly),Dominican Republic,CubaandSouth America(1% correspondingly). Pl. vivax was most common cause of malaria in patients visited Asia (87%), while recent travel to West Africa predispose patients to malaria caused by Pl. vivax in 37%, Pl. falciparum in 57% and Pl. оvale in 6% of all cases. All patients arrived from the North, South, Central Africa andDominican Republichad malaria caused by Pl. falciparum. Conclusion: in NWFD in 2012-2016 in the process of providing care to patients with malaria the following trends were marked: late referral of patients for medical care, careless collection of epidemiological data and travel history, late diagnosis of the disease, insufficient supply of antimalarial drugs and severe malaria in patients with comorbidity. Lack of adequate therapy with modern drugs has led to the lethal cases in patients with tropical malaria and the occurrence of late relapses of tertian malaria.Цель: анализ эпидемиологических и клинико-лабораторных особенностей течения завозных случаев малярии на территории Северо-Западного федерального округа (СЗФО) в 2012–2016 гг. Материалы и методы: в исследование включено 84 пациента с малярией, наблюдавшихся в стационарах СЗФО. Результаты: с 2012 по 2016 г. в СЗФО зарегистрировано 84 случая малярии – 18,9% от всех случаев по РФ (n=445): в Санкт-Петербурге (n=60), Архангельской (n=10), Мурманской (n=5), Ленинградской (n=4), Вологодской области (n=2) и по 1 – в Коми, Новгородской и Калининградской области. Недавно прибыли из азиатских стран 37% (n=31), из Западной Африки – 35% (n=30), из Северной Африки – 11% (n=7), из Южной Африки – 8% (n=7), по 3% из Восточной и Центральной Африки и по 1% из Доминиканской Республики, Кубы и Южной Америки. У прибывших из Азии в основном выявлялся Pl. vivax (87%), а у посещавших страны Западной Африки Pl. vivax – у 37%, Pl. falciparum – у 57%, Pl. оvale – у 6%. У приехавших из Северной, Южной, Центральной Африки и Доминиканы выделен только Pl. falciparum. Заключение: в СЗФО в 2012–2016 гг. в процессе оказания помощи больным малярией были отмечены следующие тенденции: позднее обращение больных за медицинской помощью, недостаточно тщательный сбор эпидемиологического анамнеза и анамнеза путешествий, несвоевременная диагностика заболевания, недостаточная обеспеченность противомалярийными препаратами и тяжелое течение малярии у пациентов с коморбидностью. Невозможность проведения адекватной терапии современными препаратами привела к развитию летальных исходов от тропической малярии и возникновению поздних рецидивов трехдневной малярии

ЗАВОЗНОЙ СЛУЧАЙ ТРОПИЧЕСКОЙ МАЛЯРИИ С ЛЕТАЛЬНЫМ ИСХОДОМ В САНКТ-ПЕТЕРБУРГЕ

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