Introduction. Liver cirrhosis (LC) is the final stage in the progression of chronic diffuse diseases. As common, late stages of LC do not respond to conservative treatment methods, so liver transplantation is the most effective method at this stage. Widespread use of transplantation in clinical practice is due to serious obstacles: a shortage of donor organs, transplant rejection, complications during the operation and the postoperative period, as well as the high cost of such an intervention. We consider bone marrow stem cell transplantation as a potential treatment for liver cirrhosis and additional clinical trials for efficacy and safety.The aim of the study was to assess the efficacy and safety of intraparenchymal transplantation of autologous MSCs from the bone marrow for the treatment of patients with cirrhosis of the liver caused by the hepatitis C virus (HCV-LC).Materials and methods. A pilot open-label non-randomized prospective study with the inclusion of 6 patients with HCV-LP. Autologous MSCs were transplanted intraparenchymally into the liver tissue at the rate of 1x106/kg body weight — 1 ml at 5 points.Results. By 6 months after transplantation, there has been a decrease in the level of bilirubin (from 36,4 μmol/L to 27 μmol/L, p=0.03), MELD scores (from 11,5 to 8, p=0.035), and an increase in platelet levels by 3 months (from 83x109 / l to 124,6x109/l, p=0,031) and 6 months (up to 119,5x109/l, p=0,031). By 6 months after transplantation, there has been no statistically significant result in changing on points on the Child-Pugh scale (p=0,181), cytolysis indicators (maintaining elevated levels of ALT (p=0,062) and AST (p=0,844)), replicative activity of the virus (рreservation of HCV RNA in the blood) (p=0,219 ). Moreover, introduction of MSCs by 6 months after transplantation did not lead to resolution of liver cirrhosis and inflammatory infiltration according to light microscopy data, as well as to resolution of sinusoidal capillarization (p=0,586) and PCI transdifferentiation into myofibroblasts (p>0,99) according to immunohistochemical studies. None of the procedures after the transplantation had an increase in body temperature, an increase in laboratory parameters, or changes in vital functions. One patient was admitted to hospital after 6 months. after MSC transplantation, deep vein thrombosis of the right leg was diagnosed.Conclusion. The positive effect of MSCs on the improvement of liver function was noted. There was no effect on the replicative activity of the virus. The continuing activity of the inflammatory process was observed. The used MSC transplantation technique is a safe procedure for patients with HCV-LC severity classes A and B and can be applied in clinical practice.
Ключевые слова: острая печеноч ная недостаточность, поражение печени, осложнения, терапия. В статье систематизирована информация об этиологии, эпидемиологии и клинических проявлениях острой печеночной недостаточности. Приведены статистические данные о частоте ее встречаемо сти при разных нозологических формах, описаны наиболее часто развивающиеся осложнения, из ложены основные подходы к терапии. Цель обзора-обобщить имеющиеся данные и улучшить ос ведомленность врачей об острой печеночной недостаточности.
Objective: to analyze the characteristics of hepatitis C virus chronic infection with concurrent cryogobulinemia, to assess the prevalence of extrahepatic diseases in the population of Belarusian patients under study.Material and methods. An open, non-randomized observational study with the inclusion of patients with hepatitis C virus (HCV) chronic infection and cryoglobulinemia (CG) was conducted.Results. The study has determined the core characteristics of HCV infection in CG patients, incidence rates and a wide array of extrahepatic diseases (EHDs), as well as HCV infection distinctive features compared to those without extrahepatic diseases.Conclusion. The revealed variety of common EHDs in HCV infection indicates that many organs and systems are involved in the pathological process and this variety should be taken into account when considering prognosis and treatment tactics.
Цель. Изучение характеристик групп хронической инфекции, вызванной вирусом гепатита С, с криоглобулинемией и васкулитом (ВГС-КГЕ-В) и криоглобулинемией без васкулита (ВГС-КГЕ), а также изучение безопасности и эффективности лечения лекарственными препаратами прямого противовирусного действия (ЛП ППД) у них на 12-й неделе после завершения лечения. Дизайн: открытое нерандомизированное наблюдательное исследование. Материалы и методы. В исследование включен 151 пациент: 41 - с ВГС-КГЕ-В и 110 - с ВГС-КГЕ. Упациентов определяли наличие антител к ВГC, уровень РНК ВГC и генотип вируса; устанавливали наличие в крови криоглобулинов; собирали демографические и эпидемиологические данные, изучали ответы на противовирусное лечение: вирусологический, иммунологический, клинический. Результаты. В группе ВГС-КГЕ-В по сравнению с ВГС-КГЕ без васкулита достоверно чаще встречались пациенты более молодого возраста и пациенты, у которых значения ревмофактора (РФ) превышают пределы нормы (р<0,05), большими значениями медианы РФ и криокрита (КК) (р<0,05). Разницы в достижении УВО12 между группами не обнаружено (р>0,05): УВО12 при ВГС-КГЕ-В - 97%, при ВГС-КГЕ без васкулита - 96%. Установлено, что в группе ВГС-КГЕ статистически значимо чаще достигался ИО12 (91%) по сравнению с группой ВГС-КГЕ-В (71%) (р<0,05). Доля пациентов в группе ВГС-КГЕ-В, достигших КО12, составила 58%. Общий полный ответ на лечение ЛП ППД был достигнут у 88% в группе ВГС-КГЕ и у 53% в группе ВГС-КГЕ-В. Заключение. ВГС-КГЕ-В характеризуется большей долей пациентов более молодого возраста и пациентов, у которых значения РФ превышают пределы верхней границы нормы (р<0,05), большими значениями медианы РФ и КК (р<0,05). Проведенный анализ установил хороший профиль безопасности ЛП ППД. Исходы лечения ЛП ППД характеризовались высокой частотой достижения УВО12 в обеих группах, более низкой частотой достижения ИО12 (71%) (р<0,05) и отсутствием КО12 в 42% в группе ВГС-КГЕ-В. The aim of this study was to investigate the characteristics of hepatitis C virus-mixed cryoglobulinemia vasculitis (HCV-MC-V) and hepatitis C virus-mixed cryoglobulinemia without vasculitis (HCV-MC) groups, the safety and effectiveness of treatment with direct-acting antiviral drugs (DAAD) at 12 weeks after completion of the treatment. Design: open-label non-randomized observational study. Materials and methods. The study included 151 patients: 41 - HCV-MC-V and 110 - HCV-MC. The following was done: the presence of antibodies to HCV, the level of HCV RNA and the genotype of HCV were determined; the presence of cryoglobulins in the blood was observed; demographic and epidemiological data were collected; responses to antiviral therapy were studied, such as: virologic (SVR12), immunological (IR12), clinical (CR12). Results. The HCV-MC-V group (in comparison with the HCV-MC) was characterized by a greater proportion of patients of a younger age; the rheumatoid factor (RF) values exceed the maximum normal limit (p<0,05), large values of the median RF and Criocrit (CC) (p<0,05) were observed. There was no difference in the achievement of SVR12 between the groups (p>0,05): SVR12 reached 97% with HCV-MC-V and 96% of HCV-MC. It was found that in the HCV-MC group, IR12 was achieved more often (91%) compared with the HCV-MC-V group (71%) (p<0,05). The proportion of patients in the HCV-MC-V group who reached CR12 was 58%. The overall complete response to treatment with DAAD was achieved in 88% in the HCV-MC group and in 53% in the HCV-MC-V group. Conclusion. HCV-MC-V with a greater proportion of younger age, in which RF exceeds the normal limits (p<0.05), large values of the median RF and CC (p<0.05). The analysis carried out a good safety profile for the DAAD. Outcomes of DAAD treatment were characterized by high SVR12 achievements, no difference in HCV-MC-V (97%) and HCV-MC groups without vasculitis (96%) (p>0.05), low achievement of IR12 (71%) (p<0,05), and the absence of CR12 in 42% in the HCV-MC-V group.
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