Is Combined Bulevirtide and Pegylated Interferon Therapy for Chronic Hepatitis D Superior over Bulevirtide Monotherapy?

Bulevirtide is a novel antiviral agent approved for suppression of chronic hepatitis D but requiring further research into optimising the treatment scheme.Aim. Comparative assessment of bulevirtide monotherapy versus combined treatment with bulevirtide and pegylat-ed interferon (PEG-IFN) using published trial data.Key points. MYR201 and MYR203 trials expose a higher frequency of HBsAg and HDV RNA extinction, as well as more effective HDV suppression for combined bulevirtide/PEG-IFN therapy compared to bulevirtide monotherapy.Conclusion. Combined bulevirtide/PEG-IFN therapy has particular advantages over bulevirtide monotherapy in patients with chronic hepatitis D. Further research is required to optimise bulevirtide dosage and duration of therapy

Demyelinating CNS processes in late post-liver transplant period

In solid organ recipients, post-transplant neurotoxicity of calcineurin inhibitors (CIs) can be manifested by brain and spinal cord demyelination with multiple sclerosis (MS)-like symptoms. Here are presented two case reports of neurological MS-like symptoms in the long-term post-liver transplant period with different underlying causes. CI neurotoxicity may resemble various neurological diseases, including MS. At the same time, liver transplant recipients can develop true MS regardless of the immunosuppressant use. In liver transplant recipients, adequate differential diagnosis of neurological complications avoids unnecessary medications and reverses severe neurological deficits by immunosuppressant conversion

ИЗУЧЕНИЕ ВОЗМОЖНОСТЕЙ ПРОТИВОВИРУСНОЙ ТЕРАПИИ ГЕПАТИТА С ТРАНСПЛАНТАТА ПЕЧЕНИ

The results of 21 courses of antiviral therapy (AT) in 18 pts with HCV infection after cadaveric liver transplan- tation have been analyzed. (One recipient received AT twice due to noncompliance and two patients re-started AT PEG-IFN monotherapy). AT included PEG–IFN alpha-2a (180 mcg/w) in 18 cases or PEG-IFN alpha-2b (1,5 mcg/kg/w) in 3 cases combined with RBV (9,9 (3,3) mg/kg/day). Since 2008 epoetin-alfa (30,000 U/w) and filgrastim (300 mcg/w) were added to correct cytopenias for all treatment duration. Sustained virologic response was achieved in 25% cases (ITT) or in 40% cases (completed 80/80/80 rule per protocol). Rapid virologic res- ponse occurred only in 2 patients with non-1 genotype HCV with respectively low viral load, and complete early virologic response (EVR) – in 10 (56%) of 18 patients. Complete EVR occurred in all non-1 genotype pts, but only in 5/13 pts with HCV genotype 1 (p = 0,036). Four pts achieved negative serum HCV RNA post 12 week of AT. The early viral dynamic is slower in AT of recurrent HCV infection in liver transplant recipients than in non-transplanted patients. Growth factors can safely and effectively be used in complex treatment of hepatitis C after liver transplantation. Обобщен собственный опыт противовирусной терапии возвратной инфекции HCV после транспланта- ции печени. С 2002 по 2010 гг. 19 пациентов получили 22 курса лечения пегилированными интерфе- ронами и рибавирином. Стойкий вирусологический ответ составил 25% при анализе в зависимости от назначенного лечения и 40% при анализе per protocol. Применение факторов роста позволило уменьшить частоту снижения доз противовирусных препаратов и перерывов в терапии. Авторы обращают внимание на медленную раннюю вирусную кинетику в изученной группе больных, что обосновывает увеличение продолжительности противовирусной терапии более 48 недель.

Система гемостаза в норме и при трансплантации печени (обзор)

The review dwells on the problem of hemostatic disorders in patients undergoing liver transplantation and their correction in the perioperative period. The physiology of the hemostatic system, disorders of the blood coagulation system in patients at various stages of liver transplantation, correction of hemostatic disorders during and after orthotopic liver transplantation are discussed. Liver transplantation is performed in patients with liver diseases in the terminal stage of liver failure. At the same time, changes in the hemostatic system of these patients pose a significant risk of developing bleeding and/or thrombosis during and after liver transplantation. The hypothesis is suggested that the personalized correction of hemostasis disorder in liver transplantation should be based on considerating the nosological forms of the liver damage, mechanisms of development of recipient’s hemostatic disorders, and the stage of the surgery.Обзор посвящен проблеме нарушений в системе гемостаза и их коррекции в периоперационном периоде у пациентов, подвергающихся трансплантации печени. Обсуждаются: физиология системы гемостаза; нарушения функции свертывающей системы крови у пациентов на различных стадиях операции трансплантации печени; коррекция нарушений гемостаза во время и после ортотопической трансплантации печени. Трансплантация печени выполняется пациентам с заболеваниями печени в терминальной стадии печеночно-клеточной недостаточности. При этом изменения в системе гемостаза этих больных представляют значительный риск развития, как кровотечений, так и тромбозов во время и после трансплантации печени. Коррекция нарушений гемостаза при трансплантации печени должна проходить с учетом нозологической формы повреждения печени, механизмов развития нарушений гемостаза реципиента и этапа операции

Изменение скорости клубочковой фильтрации у реципиентов печени после снижения экспозиции ингибиторов кальциневрина с одновременным назначением эверолимуса на протяжении первого года после конверсии иммуносупрессии

Objective: to compare changes in estimated glomerular filtration rate (eGFR) in liver recipients with initially normal and impaired eGFR within the first year after immunosuppression conversion.Materials and methods. Enrolled in the study were 215 recipients of deceased-donor livers from February 2009 to February 2020, who received everolimus with dose reduction or complete withdrawal of calcineurin inhibitors (immunosuppression conversion, ISxC) for varying periods of time. GFR was measured using the MDRD-4 formula immediately before ISxC, then 3, 6, and 12 months after orthotopic liver transplantation (LTx). One month was considered an acceptable temporary deviation from the corresponding point.Results. At the time of ISxC, 32 (15%) of 215 recipients had normal renal function. Chronic kidney disease (CKD) increased in 60% of the recipients with normal eGFR by the end of the first year following ISxC; the fall in eGFR was particularly pronounced in older recipients. In the group with a baseline eGFR of 60–89 mL/min/1.73 m2, eGFR normalized in 62% of cases within 12 months; 28% of cases had no changes in renal function. In the subgroup with a pronounced decrease in eGFR at the time of ISxC, increased eGFR was observed as early as 1 month after ISxC, and the maximum was recorded after 3–6 months. The mean eGFR relative to baseline by month 3 after eGFR were higher for ISxC that was done in the first 2 months after LTx (19.7 ± 15.7 ml/minute/1.73 m2) than for ISxC done in the long-term period after LTx (10.1 ± 8.7 ml/minute/1.73 m2, p < 0.05).Conclusion. Changes in eGFR in liver recipients receiving EVR plus low-dose calcineurin inhibitor (CNI) depend on baseline eGFR and are multidirectional. The use of ISxC in the early post-LTx period led to a more pronounced improvement in eGFR. Maximal changes in eGFR were observed by 3–6 months after ISxC.Цель. Сравнение изменений расчетной скорости клубочковой фильтрации (рСКФ) у реципиентов печени с исходно нормальной и нарушенной рСКФ на протяжении первого года после конверсии иммуносупрессивной терапии.Материалы и методы. В исследование включены 215 реципиентов после трансплантации печени (ТП) от посмертного донора с февраля 2009 г. по февраль 2020 г., получавших на протяжении различного времени эверолимус со снижением дозы или полной отменой ИК (конверсия иммуносупрессии – КИС). СКФ рассчитывалась по формуле MDRD-4 непосредственно перед КИС, через 3, 6, и 12 месяцев после ТП. Допустимым временным отклонением от соответствующей точки считался 1 месяц.Результаты. На момент КИС у 32 (15%) из 215 реципиентов наблюдалась нормальная функция почек. У 60% реципиентов с нормальной рСКФ к концу первого года после КИС наблюдалось увеличение степени ХБП; снижение рСКФ особенно выражено у реципиентов старшего возраста. В группе с исходной рСКФ 60–89 мл/мин/1,73 м2 в 62% случаев в течение 12 месяцев наблюдалась нормализация рСКФ; в 28% случаев изменения функции почек не наблюдалось. В подгруппе с выраженным снижением рСКФ на момент КИС увеличение рСКФ наблюдалось уже через 1 месяц после КИС, а максимума – через 3–6 месяцев. Средние значения увеличения рСКФ по отношению к исходному уровню к 3-му месяцу после КИС были выше при КИС, проведенной в первые 2 месяца после ТП (19,7 ± 15,7 мл/мин/1,73 м2), чем при КИС, проведенной в отдаленные сроки после ТП (10,1 ± 8,7 мл/мин/1,73 м2, p < 0,05).Заключение. Изменения рСКФ у реципиентов печени, которые получают ЭВР в сочетании со сниженной дозой ИК, зависят от исходного уровня рСКФ и носят разнонаправленный характер. Проведение КИС в ранние сроки после ТП приводило к более выраженному улучшению рСКФ. Максимальные изменения рСКФ наблюдались к 3–6 месяцам после КИС

Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation

Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017)

The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient