К ВОПРОСУ О ТРАНСПЛАНТАЦИИ ПЕЧЕНИ У БОЛЬНЫХ ГЕПАТОЦЕЛЛЮЛЯРНОЙ КАРЦИНОМОЙ (КРАТКИЙ ОБЗОР ЛИТЕРАТУРЫ)

Гепатоцеллюлярная карцинома (ГЦК) – одна из наиболее распространенных опухолей, занимающая лидирующие позиции в структуре летальности от онкологического заболевания. Первичный рак печени устойчиво ассоциируется с наличием хронического диффузного заболевания печени – вирусного гепатита и цирроза. Ортотопическая трансплантация печени – альтернативный и, возможно – оптимальный метод лечения ГЦК, так как в результате операции полностью удаляется пораженный орган и предраковое заболевание. Отдаленные результаты ОТП зависят от стадии опухолевого поражения, инвазии опухоли в сосуды печени. Золотым стандартом в определении показаний к ОТП при ГЦК принято считать «Миланские критерии» и «Барселонскую» классификацию, обеспечивающие прекрасные отдаленные результаты. Вместе с тем, многими авторами данные критерии признаются излишне строгими, необоснованно лишающими значительную часть больных перспективы трансплантации печени

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

Screening and Early Diagnosis of Hepatocellular Cancer and Optimization of Diagnostic Imaging Techniques: A Review and Conclusion of the Expert Panel

Аim: to describe modern approaches for screening and early diagnosis of hepatocellular carcinoma (HCC).Key points. Screening for HCC in high-risk groups (cirrhosis of any etiology, patients with chronic viral hepatitis B and patients with F3 liver fibrosis) should be organized as regular (every 6 months) liver ultrasound in combination with determination of the serum alpha-fetoprotein (AFP) level. At an AFP level of ≥ 20 ng/ml, even in the absence of changes according to ultrasound data, it is advisable to perform MRI with a hepatospecific contrast agent (gadoxetic acid) which makes it possible to detect very small focal liver lesions. If focal liver lesions of 1–2 cm are detected on ultrasound, additional imaging of the liver using MRI with a hepatospecific contrast agent gadoxetic acid helps to identify HCC at an earlier stage or high degree dysplastic nodes. When planning surgical treatment and liver transplantation, it is preferable to use MRI with a hepatospecific contrast agent, since the presence of the hepatobiliary phase may allow the detection of additional smaller focal liver lesions and assess the nature of the focal liver lesion. When a patient is included in the waiting list for liver transplantation, the optimal frequency of liver MRI is 1 time in 3 months.Conclusion. MRI with hepatospecific contrast agent gadoxetic acid is effective in screening, early diagnosis and treatment planning for HCC

IMMUNOLOGICAL TOLERANCE IN ORGAN TRANSPLANTATION

Modeling of  immune tolerance will  eliminate the  need  for  taking medications to prevent rejection. This  review of available literature covers the immune mechanisms of allograft rejection and the ways of tolerance induction. The role of mesenchymal stem  cells and using them for tolerance development have been discussed. The authors also draw attention to the fact  that  blood transfusion from an organ donor  leads to a decreased  intensity of the immune response to donor cells in transplantation

Clinical Recommendations of the Northwest Society for Enteral and Parenteral Nutrition, Interregional Association for Emergency Surgery, Russian Gastroenterological Association, Union of Rehabilitation Therapists of Russia and Russian Transplantation Society on Diagnosis and Treatment of Short Bowel Syndrome-Associated Intestinal Failure in Adults

Aim. Current clinical recommendations address the epidemiology, causes, clinical manifestations and pathogenesis of possible immediate and long-term complications, as well as the problematic issues related to treatment and rehabilitation of adult short bowel syndrome patients.Key points. Short bowel syndrome (SBS) is a symptom complex of impaired digestion caused by the reduction of small intestine absorptive surface and manifested by intestinal failure (IF) of various severity (maldigestion and malabsorption) developing into malnutrition and systemic somatogenic disorders. The vital strategic aspects of its treatment are the personalisation of liquid, macro- and micronutrients consumption as well as avoidance of intestinal failure- and parenteral nutrition-associated complications. Various nutritional support regimes and the indications for infusion therapy and maintenance parenteral nutrition are considered in this patient category, also in outpatient settings. To mitigate the dependence on intravenous fluid- and nutrient administration and attain enteral autonomy in SBS-IF patients, the use of recombinant glucagon-like peptide-2 (GLP-2) is justified as exerting a pronounced trophic effect on the epithelial regenerative potential as well as structural and functional adaptation of intestinal mucosa. The SBS-IF patients prescribed with home parenteral nutrition and/or their caregivers should be trained in a special programme that covers the catheter care, preparation of infusion solutions and nutrient mixture container, infusion pump operation as well as the prevention, recognition and management of complications. The main referral indications for small bowel transplantation (SBT) are: fast-progressing cholestatic liver disease-complicated irreversible intestinal failure; thrombosis of two or more central venous conduits used for parenteral nutrition; recurrent catheter-associated bloodstream infection.Conclusion. Current recommendations on diagnosis and treatment as well as the developed criteria of medical aid quality assessment are applicable at different levels of healthcare

Vascular complications after orthotopic liver transplantation

Vascular complications (VCs) comprise one of the most serious problems in liver transplantation. This is the next reason of graft loss after primary graft non-function, with the majority of complications being arterial by etiology. VCs significantly decrease the graft and patient survival, contribute to the incidence of retransplantation. This review focuses on the epidemiology, etiology, diagnostics, and treatment of VCs

Biomarkers of tolerance and immunological monitoring in liver transplantation

Introduction. We reviewed the literature data on clinical and laboratory parameters that allow predicting the development of operational tolerance in liver transplant recipients after their complete weaning from immunosuppressive therapy. The aim was to identify possible biomarkers of tolerance in liver transplant recipients with the successful complete weaning from immunosuppression for subsequent implementation in routine clinical practice. The cellular, humoral, and molecular markers of the liver transplant recipients who were completely withdrawn from immunosuppressive therapy without the development of graft dysfunction were estimated. The authors underlined the necessity of clinical trials for identifying biomarkers of the operational tolerance development

CMV-infection in patients after liver transplantation

The article presents an analysis of the current state of the problem antiviral therapy CMV-infection in patients undergoing liver transplantation. We retrospectively reviewed the experience of the Moscow Center for liver transplantation in the prevention of cytomegalovirus disease in liver recipients. We describe the clinical examples of different flow CMV-infection in patients after liver transplantation and therapy approaches