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Introduction. One of the serious complications after transplantation of solid organs and bone marrow is the development of post-transplant lymphoproliferative diseases.Clinical case. To evaluate the course of post-transplant lymphoproliferative diseases in the long-term in a liver transplant recipient after conversion of immunosuppressive therapy from tacrolimus to everolimus. We analyze a case of generalized primary plasmacytoma of lymph nodes with bone marrow involvement in a patient after liver transplantation.Results. After conversion of immunosuppression we observed a rapid positive trend: decreasing size of lymph nodes and regression of the level of paraprotein down to its complete disappearance. There were neither adverse events associated with everolimus for four years, nor signs of immunosuppression insufficiency.Conclusion. This Case Report is the first description of a long-term remission of nodal plasmacytoma that developed in a liver transplant recipient after complete withdrawal of calcineurin inhibitors and administration of everolimus. We suggest that the regression of post-transplant lymphoproliferative diseases after replacing calcineurin inhibitors with everolimus is associated not only with the minimization of calcineurin inhibitors exposure, but also with the antitumor effect of the everolimus itself, which prompts us to discuss the possibilities of expanding its clinical application.

Background. The problem of thromboses, including those associated with impaired hemostasis system, is relevant in orthotopic liver transplantation.Aim. To present the experience of intraoperative use of protein C during orthotopic liver transplantation in a patient with a high risk of recurrent portal vein thrombosis.Results. During orthotopic liver transplantation in a patient with a high risk of recurrent portal vein thrombosis, the intraoperative administration of the protein C preparation at a dosage of 500 IU contributed to the increase in plasma level of protein C by 48%. In the post-transplant period, recurrent portal vein thrombosis was not observed. Conclusion. Intraoperative administration of protein C in combination with basic therapy for orthotopic liver transplantation helps to prevent recurrent portal vein thrombosis.

Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.

Liver transplantation is rightly considered the only radical treatment for terminal chronic liver diseases and patients with acute liver failure. However, despite the accumulated experience in the management of patients in this group, the level of complications development remains at a fairly high level. The success of the correction of emerging pathological conditions largely depends on the timing of their diagnosis. Since complications developing after liver transplantation most often do not have specific clinical and biochemical manifestations, the use of imaging research methods plays a key role in assessing the state of the transplanted organ at all stages of the postoperative period. Among all instrumental methods, ultrasound examination using Doppler techniques, carried out hourly directly in the intensive care unit, with an accuracy of 97 % and a specificity of up to 100 %, makes it possible to detect vascular post-transplant complications as soon as possible. Their timely correction avoids the loss of the graft. The use of dynamic observation contributes to differential diagnosis in identifying non-vascular complications at different stages of the postoperative period. The use of modern techniques greatly expands the possibilities of echography. Thus, the use of contrast enhancement not only shortens the study time, but also increases the sensitivity of Dopplerography in assessing the patency of the vascular bed, especially in patients with decreased central hemodynamics. The use of ARFI-elastography techniques in patients in the late postoperative period makes it possible to objectively assess the severity of hepatic graft fibrosis.

Rationale. Hepatorenal syndrome is a threatening complication in patients with liver cirrhosis and portal hypertension. The occurrence of renal dysfunction associated with hepatorenal syndrome manifestations significantly affects the condition severity, the disease duration, and the survival time during the waiting period for liver transplantation.The study purpose was to investigate the potential of a complex ultrasonography examination in the assessment of intrarenal hemodynamic impairments in patients with various diffuse liver diseases.Material and methods. The ultrasound examination results of 167 patients were analyzed. The 1st group included 28 patients with confirmed diffuse liver diseases of viral etiology who did not have signs of cirrhosis formation, the 2nd group included 139 patients with liver cirrhosis due to diffuse liver diseases of various etiologies, and the 3-rd group included 137 patients who had previously been in the 2nd group in whom orthotopic liver transplantation was performed.Results. The study revealed a statistically significant increase in the incidence of secondary hemodynamic impairments in kidney function in patients with liver cirrhosis and no relationship of their severity and incidence to the disease etiology, and also to such markers of the portal hypertension severity as splenomegaly, ascites, and portal vein thrombosis.Conclusions. The resistive index measured on the renal arterial branches by Doppler ultrasound, has a certain predictive value in relation to hepatorenal syndrome in patients with liver cirrhosis of various origins. This also makes it possible to timely identify a group of patients at a high risk of developing severe renal dysfunction and to assess the efficacy of the treatment that has been given.

Situs inversus is a rare mirror transposition of internal organs relative to the median plane. Liver transplantation in situs inversus is a serious medical challenge imposed by an abnormal arrangement of the recipient's organs. Aim . Clinical description of a successful cadaveric liver transplantation in an adult patient with situs inversus and portal vein thrombosis. Key points . A 32 years-old patient with situs inversus , chronic hepatitis B/D-induced liver cirrhosis and portal vein thrombosis had cadaveric liver transplantation, with the transplant reoriented in abdominal cavity 90° clockwise relative to the median plane. End-to-side cavocaval anastomosis was formed between the donor's retrohepatic and the recipient's main inferior vena cava, with successive portal and arterial anastomoses and complete donor liver reperfusion. A biliary reconstruction was performed with an end-to-end biliobiliary anastomosis. The surgery duration comprised 5 h 20 min, intraoperative blood loss — 2000 mL, cold ischemia time — 4 h. The patient was discharged on the 10 th day after surgery in satisfactory condition. Conclusion . Situs inversus is not a contraindication to liver transplantation.

Introduction. The development of invasive candidiasis leads to high mortality after liver transplantation. Choosing an effective prophylaxis is an important task.The study purpose was to compare the results of invasive candidiasis prevention with anidulafungin vs. the lipid formulation of amphotericin B in high-risk patients in the early postoperative period after liver transplantation. Material and methods. The study included 80 patients with risk factors for the development of invasive mycosis who underwent liver transplantation. Patients were divided into 2 groups. In the first group (n = 40), anidulafungin was prescribed for prophylaxis; in the 2nd group (n = 40), the lipid complex of amphotericin B was used.Results. The most common of Candida spp. isolated in the patients of our study, as expected, was Candida albicans accounting for 31.2%, significantly less than a half. Neither fungal infection breakthrough nor invasive mycosis development were reported in any patient. In group 2, renal replacement therapy was significantly more frequently used. In two cases, the amphotericin B lipid complex was canceled and the conversion to echinocandin was undertaken due to the occurrence of adverse events (chills and fever) associated, in our opinion, with the drug used. Conclusions. 1. Patients after liver transplantation with 2 or more risk factors have absolute indications to invasive mycosis prevention. 2. Anidulafungin and the lipid formulation of amphotericin B are effective for prophylaxis and prevention of fungal infection breakthrough. 3. Anidulafungin has an advantage in safety over the lipid formulation of amphotericin B.

Changes in current scientific literature and regulatory documents related to the issues of infectious safety in organ and tissue donation have been analyzed. The suggestions have been given for changing the existing practices to meet new challenges. Data on threats to the safety of organ and tissue donation associated with the COVID-19 pandemic have been presented.

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.

Aim. To identify trends in the structure of patients with liver diseases, in particular hepatocellular cancer (HCC), by analysing the experience of two specialised medical centres.Materials and methods. A retrospective analysis of the medical records of hepatological patients who sought medical treatment at to the V.Kh. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology of the Sechenov University in 2013, 2014 and 2017 (total 2459 patients) was carried out. The number of patients with chronic viral hepatitis (CVH) was 651, with non-alcoholic fatty liver disease (NAFLD) — 590, with alcoholic liver disease (ALD) — 66, with autoimmune liver diseases — 416, with liver cirrhosis (LC) of any etiology 407, other liver diseases — 329. A retrospective analysis of the medical records of patients with HCC who were examined and treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2008 to 2017 (n = 86) was carried out.Results. The ratio of patients with chronic hepatitis C and B in 2013–2017 significantly changed. An almost twofold decrease in the number of patients with chronic hepatitis C (210 patients in 2013 and 141 patients in 2017) and an increase in the number of patients with chronic hepatitis B (20 patients in 2013 and 45 patients in 2017) was observed. An almost twofold increase in the total number of NAFLD patients was detected (163 patients in 2013 and 276 patients in 2017). The number of ALD patients increased from 12 patients in 2013 to 31 patients in 2017. The proportion of patients with autoimmune liver diseases in the overall structure of patients who applied to the department was 20 % in 2013, 13.6 % in 2014 and 10.8 % in 2017. An almost twofold decrease in the number of patients with alcoholic LC and LC associated with HBV was observed (73 patients and 17 patients in 2013 and 38 patients and 6 patients in 2017, respectively) as well as a noticeable increase in the number of patients with alcoholic LC and LC associated with HCV (6 patients and 51 patients in 2013 and 26 patients and 75 patients in 2017, respectively). In the analysis of HCC patients, the ratio of men to women was 3:1 (64 men and 22 women), the median age was 54.5 years (IQR 48–59). The median time from the establishment of chronic liver disease to the detection of HCC was 7.5 years (IQR 3–14.5). In 86 % of cases, the HCC development was preceded by cirrhosis (Child-Pugh A: n = 24; Child-Pugh B: n = 30; Child-Pugh C: n = 20), in 14 % — by chronic hepatitis. Viral liver lesions were the leading cause of HCC in 79 % (n = 68), ALD in 4 % (n = 3), NAFLD in 1 % (n = 1), AIH in 1 % (n = 1). In 10 % (n = 9), a combined liver lesion was observed, in 5 % (n = 4), no previous liver disease was known. The highest five-year survival rate (100 %) was found in the group of patients who received antiviral therapy (AVT) before and after liver transplantation.Conclusions. NAFLD, ALD, and chronic hepatitis B patients began to seek medical help more frequently. An increase in the number of patients with autoimmune LC and LC associated with chronic hepatitis C virus (HCV) infection was observed. The conducted analysis of trends in the structure of HCC patients showed that chronic HCV and HBV infection is the main prerequisite for the development of cancer. Liver transplantation is the most effective treatment for HCC. AVT before and after liver transplantation allows a statistically significant increase in the five-year posttransplant survival of HCC patients with chronic hepatitis C to be achieved.

Introduction. Recent studies have indicated an increased incidence of thrombotic vascular complications after liver transplantation. The reasons may be associated with surgical technique and “unbalanced” hemostasis in patients with diffuse liver diseases. The imbalance is determined by the deficiency of physiological procoagulants and anticoagulants due to a reduced protein-synthesis function of the liver in chronic hepatocyte injury. At the same time, 90% of all spontaneous antithrombin activity is associated with antithrombin III.Aim. The aim of the study was to evaluate the efficacy of using antithrombin III concentrate in liver transplant patients.Material and methods. A retrospective study included 46 patients undergoing liver transplantation who had nonocclusive thrombosis in the portal vein system prior to surgery and postoperative venous or arterial thrombosis.Results. The treatment results were compared between the group with antithrombin III concentrate and the control group in patients with portal vein thrombosis before surgery and postoperative venous or arterial thrombosis; the antithrombin III activity dynamics in the early postoperative period was assessed; the incidence of infectious, and vascular complications and the mortality rates were analyzed.Conclusion. The antithrombin III concentrate administration during liver transplantation and in the postoperative period contributes to a rapid normalization of antithrombin III activity in blood, the decrease in mortality and in the incidence of infectious and thrombotic complication rates.

Objective. The study objective was to assess the scintigraphy potential in the evaluation of portal hypertension and the severity of liver damage in diffuse diseases and after liver transplantation.Material and methods. The study enrolled 325 patients suffering from hepatitis and liver cirrhosis of various etiology and severity, including those after liver transplantation, namely, the patients with hepatitis (n=96), patients with liver cirrhosis of Child–Pugh class A (n=24), class B (n=87), and class C (n=118); 11 more healthy volunteers without clinical and laboratory signs of diffuse liver disease were enrolled as controls. The assessment of liver reticuloendothelial system was performed by scintigraphy with (99m)Tc-phytate colloid in a static planar mode and "whole body" mode by SPECT (Infinia II, GE).Results. In contrast to the control group, significant radionuclide signs of hepatosplenomegaly were revealed with the predominant functional activity of the left lobe; the liver function was found impaired that correlated with the cirrhosis severity evaluated according to the Child–Pugh Сlassification. The analysis of scintigraphy quantitative parameters showed that the most informative of them were the intensity of radiopharmaceutical accumulation in the spleen (S%) and in bone marrow (Вm%), and the radiopharmaceutical uptake by the reticuloendothelial cells of the liver and spleen in percentage from the administered activity (Lwb%, Swb%). Depending on the cirrhosis severity assessed by the Child–Pugh Score, the changes in quantitative parameters were accompanied by a progressive enlargement of the spleen, liver left lobe, the increase of (99m)Tc-phytate uptake by the bone marrow with a decreased radiopharmaceutical uptake by the liver. The study results showed that among the Child–Pugh class C patients, the impairment of liver reticuloendothelial function was more pronounced in the patients with cirrhosis of viral and mixed etiology, when compared to those with alcoholic cirrhosis.Conclusion. The paper has identified the most informative parameters characterizing portal hypertension and the reticuloendothelial function for all Child–Pugh defined classes of cirrhosis. These parameters include the increase of (99m) Tc-phytate accumulation in the spleen (S%) and bone marrow (Bm%); the liver and spleen uptake of the radiopharmaceutical in percentage from the administered activity (Lwb%, Swb%). The calculation of the remaining parameters is necessary for a detailed description of the organ function and for the assessment of the portal hypertension severity in repeated studies.Summary. Criteria for the objective assessment of reticuloendothelial function and portal hypertension in diffuse liver diseases, including after liver transplantation, have been developed. Contrary to the control group, in patients with diffuse liver diseases, the radionuclide signs of hepatosplenomegaly (or a decreased liver size) with a predominant functional activity of the left lobe were identified, as were the changes in the quantitative parameters of the radiopharmaceutical uptake by the liver (Lwb%), including the radiopharmaceutical accumulation in the liver left lobe (Ll%), spleen (Swb%), bone marrow (Bm%), and the liver-to-spleen area ratio (Lar/Sar). The informative and reliable (p

Worldwide, there is a trend towards an increase in the number of patients waiting for liver transplantation, despite an increase in the total number of liver transplantation operations. Solving the problem of donor organ shortage is possible through the use of organs from marginal donors: organs removed after cardiac arrest, organs with a high percentage of steatosis, organs from donors over the age of 60 years. The main reason for refusing to use them is the risk of severe complications and an unfavorable outcome of the operation. Static cold preservation today is the main method of protecting donor organs from thermal damage, which possesses rather effective protective properties. At the same time, the duration of cold preservation has a limited time interval. There is always uncertainty about the viability of the organ. Modern methods for assessing donor organs such as donor history, laboratory data, visual examination and morphology, do not reliably predict liver function after transplantation. In this regard, the development of methods for preserving the organ after removing, which do not degrade the quality of the organ or even are capable of restoring the lost functions, is relevant. The machine perfusion of the liver is one of the new concepts aimed at solving this problem. The article highlights the international experience of using the machine perfusion of the donor liver over the past 15 years. Machine perfusion is a promising trend of transplantation development, which allows reducing the shortage of donor organs and improving their quality.

Aim. The aim of the study is to determine the effectiveness of liver transplantation (LT) in the treatment of unresectable hepatocellular carcinoma (HCC) occurred in normal liver.Material and methods. 6 patients with unresectable HCC underwent orthotopic liver transplantation (OLT). The long-term OLT results were compared with survival results of liver resection in patients with late stage HCC.Results. Hepatocellular carcinoma is one of the most common types of cancer, which occurs mainly in patients with liver cirrhosis and chronic viral hepatitis. Only about 10 % of HCC develops in non-cirrhotic liver among young and somatically healthy patients. 1-, 3-, 5-year recurrence-free and overall survival in LT group was significantly better than in the control group.Conclusion. LT is indicated for patients with unresectable HCC in non-cirrhotic liver and its extrahepatic localization. A large tumor size and macrovascular invasion should not be a contraindication for LT in such patients.

Donor organ shortage stimulated an active use of donors with expanded evaluation criteria. The main evaluation method was a histological examination of liver graft biopsy specimens before (time-zero biopsy) and after reperfusion (time-1 biopsy). Severe ischemic and reperfusion injuries among recipients who received a liver graft made 20.4% and 16.6% respectively. The study showed no impact of small droplet, medium droplet, or even large droplet steatosis (less than 50%) on graft reperfusion injury.

Aim. The aim of the study was to investigate the endoscopic diagnostic and treatment techniques for biliary complications after orthotopic liver transplantation, their efficacy and safety. Material and methods. The study was based on the results of endoscopic treatment of 29 patients with biliary complications occurred after orthotopic liver transplantation in N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from December 2001 to January 2017. Conclusions. The state-of-the-art methods of therapeutic endoscopy enable a successful treatment of most cases of biliary strictures and biliary-biliary anastomosis incompetence, thus achieving good long-term results using a minimally invasive methodology.

The article presents the experience of direct-acting antiviral (DAA) drug treatment for hepatitis C in the patients after liver transplantation. The end-stage liver disease caused by hepatitis C is the main indication for orthotopic liver transplantation (OLT). In 2013, the first agent in the class of antiviral drugs directly acting on hepatitis C virus (HCV) was introduced into clinical practice. That was sofosbuvir, a HCV polymerase inhibitor, that could be used without interferon alfa. Materials and methods . The study enrolled 33 liver transplant recipients with recurrent hepatitis C. Thirty-five courses of antiviral therapy (AT) were conducted with sofosbuvir being one of AT components. Results. By the time of analysis, 21 patients had completed the antiviral therapy. All the patients showed an initial response to the antiviral therapy, HCV aviremia was achieved. In 3 patients, with the evaluable sustained virologic response (SVR), a renewed HCV replication was observed in the first weeks after the AT completion. Conclusion. The new direct-acting antiviral drugs offer an effective antiviral therapy to all liver graft recipients with recurrent HCV.

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.

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.

To perform retrospective analysis of treatment of postoperative ventral hernias (PVH) in kidney and extrarenal organs recipients, to assess its safety and effectiveness.Hernia repair has been performed in 84 PVH patients for the period from May 2006 to November 2017. The main group consisted of 41 patients (24 males, 17 females, mean age 55 (44; 59)) years with PVH due to previous transplantation. The control group included 43 PVH patients (21 males, 22 females, mean age 51 (50, 56)) years without previous transplantation.Incidence of surgical complications was similar in two groups: 63.4% in group 1 vs. 53.5% in group 2 (p0.05). There were no significant differences in the incidence of surgical complications depending on immunosuppressive therapy and synthetic endoprosthesis deployment technique.Treatment of postoperative ventral hernias using synthetic endoprostheses in recipients of solid organs is effective and safe and should be considered as a preferable in treatment of this pathology.Относительно высокая частота послеоперационных вентральных грыж (ПОВГ) после трансплантации абдоминальных органов требует разработки эффективных и безопасных методов. Цель исследования - ретроспективный анализ результатов, оценка безопасности и эффективности лечения ПОВГ у реципиентов почки, поджелудочной железы и печени, получающих иммуносупрессивную терапию. Материал и методы. С мая 2006 г. по ноябрь 2017 г. у 84 пациентов с ПОВГ выполнена протезирующая герниопластика синтетическим имплантатом. В 1-ю группу (исследуемая группа) вошел 41 пациент (24 мужчины, 17 женщин; средний возраст 55 лет (44; 59 лет)) с ПОВГ как отдаленным осложнением после трансплантации солидных органов на фоне приема иммуносупрессивных препаратов. 2-ю (контрольная группа) составили 43 пациента (21 мужчина, 22 женщины; средний возраст 51 год (50; 56 лет)) с ПОВГ без трансплантации органов в анамнезе, которые не получали иммуносупрессивную терапию. Результаты. Статистически достоверных различий в частоте хирургических осложнений в группах не отмечено: частота послеоперационных хирургических осложнений в 1-й группе составила 63,4%, во 2-й группе - 53,5% (р0,05). Достоверных различий в частоте хирургических осложнений в зависимости от проводимой иммуносупрессивной терапии и способа имплантации синтетического эндопротеза не выявлено. Выводы. Лечение ПОВГ с использованием синтетических эндопротезов у реципиентов солидных органов является эффективным и безопасным и должно рассматриваться в качестве метода выбора при указанной патологии.