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Background. Liver transplantation is currently the most effective method to treat diseases with end-stage liver failure. Complications are most often associated with the initially severe patient condition, imperfect organ preservation methods, the surgical management per se, and immune system incompetence. The most common complications of transplantation include ischemic reperfusion injury, which occurs to some or another extent in each transplanted organ and worsens the course of the postoperative period. The process is based on complex pathophysiological mechanisms of cell damage due to ischemia and inflammation caused by reperfusion.Objective. To summarize current data on the mechanisms of the ischemic reperfusion injury development in liver transplantation and to find the ways to reduce adverse effects.Material and methods. The analysis of data from foreign and homeland experimental and clinical studies on the pathogenesis of ischemic reperfusion injury in liver transplantation has been performed. The search for literature data was carried out in international databases (PubMed/MedLine, ResearchGate, as well as in the scientific electronic library of Russia (eLibrary.RU) for the period from 2020-2024.Conclusion. The analyzed publications have provided various algorithms for the preservation of donor organs, including those using machine perfusion.

Background. The urgency of the unmet need for transplant care dictates the necessity to use organs from suboptimal donors. Machine perfusion, which is actively developing at the present time, is designated to solve this problem. The literature presents novel technologies of ex vivo and in vivo machine perfusion of donor organs, which make it possible to improve their functions and perform a successful transplant. The most promising areas of research both in animals and in humans may be identified by reviewing the literature sources on this subject.The aim was to analyze the world experience of using therapeutic agents in machine perfusion of donor organsMaterial and methods: sources from 2015 to 2023 found in PubMed, Google Scholar, eLibrary databasesConclusion. The rapid progress in lung, liver and kidney transplantation has made it possible to use grafts from asystolic donors for patients in urgent need of donor organs. In turn, these advances have also prompted the study of potential therapeutic agents that can be used during perfusion.

Relevance. The choice of biliary anastomosis is the main factor determining the risk of developing biliary complications after orthotopic liver transplantation. The two most common forms of biliary tract reconstruction are choledocholedochostomy (duct-to-duct anastomosis) and choledochoeunostomy (connection of the bile duct to the jejunum). The choice of biliary tract reconstruction is determined by a variety of factors, including the underlying pathology of the liver, the size of the bile ducts of the donor and recipient, previous transplantation or previous biliary tract surgery, as well as the preferences of the surgeon performing the operation. Despite the correctly chosen method of reconstruction, complications such as strictures, lithiasis, biloma, and bile leakage occur infrequently.Objective: to present a review of the literature on methods of diagnosis and treatment of biliary complications after liver transplantation.Materials and methods. The analysis of literary sources in English and Russian from 2010 to 2023 on this topic in the databases PubMed, MEDLINE, Google Scholar was carried out. The review highlights clinical studies, as well as literature reviews on similar topics with an emphasis on the treatment and diagnosis of biliary complications.Conclusion. The problem of biliary complications of liver transplantation remains relevant and unresolved to the end. Noninvasive imaging techniques for complications arising after biliary tract surgery have prospects for development. The tactics of percutaneous, endoscopic and open interventions on the biliary graft tree require further improvement.

Introduction. Hepatocellular cancer is the most frequent primary malignant neoplasm of the liver, developing against the background of viral hepatitis, alcohol abuse, metabolic disorders, cirrhosis. Most often hepatocellular cancer is diagnosed at late stages of the disease, when patients are no longer subject to specific treatment. The priority method of treatment of early stages remains surgical. In the absence of cirrhosis or with compensated cirrhosis the best option is liver resection, in other cases orthotopic liver transplantation is performed. However, when hepatocellular cancer is diagnosed, most patients fall outside the Milan criteria, and the bridge to orthotopic liver transplantation is down-stage therapy. Bridge therapy is used to treat hepatocellular cancer while awaiting liver transplantation and aims to prevent stage progression. The probability of progression of hepatocellular cancer after orthotopic liver transplantation within the first two years is about 75% and about 10% is detected after the fourth year. Progression of hepatocellular cancer remains the main factor limiting the life expectancy of patients after orthotopic liver transplantation.The aim of the study: to evaluate the results of antitumor treatment of patients with hepatocellular cancer progression after liver transplantation.Materials and methods. We evaluated the results of treatment of 50 patients with hepatocellular cancer progression after orthotopic liver transplantation, who were treated on the basis of FGBU NMI Center of Oncology named after N.N. Blokhin. N.N. Blokhin Oncology Center in the period from 2009 to 2020. We analyzed and evaluated overall and recurrence-free survival depending on the bridge therapy, type of treatment, presence of vascular invasion and portal vein thrombosis.Results. According to the results of bridge therapy, hepatocellular cancer stage progression was observed in 9 patients, stabilization - in 17 patients, partial/complete response – in 9 patients. The median recurrence-free survival of patients who received bridge therapy and down-stage therapy was 23.6 months; among patients who did not, it was 35.6 months. The median overall survival with surgical treatment was 79.8 months, whereas with radiation therapy it was 17.2 months. Conclusions. In the studied group of patients the treatment was tolerated satisfactorily. Optimization of immunosuppression protocol and modification of dose regimens of systemic therapy is considered as a condition for treatment, which leads to improvement of long-term treatment results (overall and relapse-free survival).

Background. The terminal stages of chronic hepatitis C remain the main indication for liver transplantation in Russia and in the world.Aim. To retrospectively evaluate the changes in the waiting list of liver transplantation that occurred during 22 years of work of the Department for Liver Transplantation at N.V. Sklifosovsky Research Institute for Emergency Medicine in relation to patients with anti-HCV+; and to study the survival rate of anti-HCV+ after liver transplantation, and peculiarities of the course of recurrent HCV infection and virological outcomes of modern antiviral therapy.Material and methods. We analyzed the results of anti-HCV+ liver transplantations from a deceased donors (n=400) operated in the Department for Liver Transplantation at N.V. Sklifosovsky Research Institute for Emergency Medicine for 22 years. Changes in the Waiting List structure, recipient survival and antiviral therapy efficacy were studied.Results. The proportion of anti-HCV+ recipients decreased from 44.3% (period from 2007 to 2019) to 34.1% (from 2020 to 2022, p=0.0027). Survival of anti-HCV+ recipients without HCC is currently comparable to survival of non-infectious non-HCC recipients. The 5-year survival of anti-HCV+ recipients without HCC at the time of liver transplantation was 84%, and the 10-year survival was 76%. The 3and 5-year survival rates of recipients without HCC at the time of liver transplantation who had surgery before August 2016 were lower (80% and 77%, respectively) than the 3and 5-year survival rates (91%) of liver transplant recipients operated on later than this date (p=0.01). Before August 2016, recurrence of HCV infection occurred in > 90% of anti-HCV+ recipients with known HCV RNA status after liver transplantation. Spontaneous clearance of HCV RNA after liver transplantation was observed in 2.1% of cases. In recent years, the incidence of recurrent HCV infection after liver transplantation has decreased significantly (~25% in 2021–22). The use of modern direct acting antiviral regimens results in >95% viral eradication after the 1st course. The emergence of drug resistance polymorphisms in patients who have had unsuccessful experience of direct acting antiviral before liver transplantation is not an obstacle to the success of direct acting antiviral treatment after liver transplantation.Conclusion. The possibility of a rapid and safe cure for HCV infection against the backdrop of a shortage of donor organs necessitates a revision of the documents regulating organ donation, which should make organs from donors with antiHCV in the blood available for transplantation.

Background. Organ transplantation is the optimal decision for patients in the end stage of many diseases. Certain conditions are required for the transportation and preservation of a donor organ after explantation, including factors such as temperature, pressure, and preservative solution. All currently available methods of preservation of donor organs are aimed at maximizing the complete preservation of the functional state of the graft from the moment of its removal to implantation and reperfusion in the recipient's body.Aim. The purpose of this review is to provide up-to-date information on the results of the studies performed in order to decide on the preferred method of organ preservation.Material and methods. An analysis of literature sources in English and Russian from 2009 to 2023 on this topic was performed in the databases PubMed, MEDLINE, Google Scholar. The review highlights the results of preclinical (on animal models) and clinical studies, as well as achievements in the field of ex-vivo machine perfusion with an emphasis on machine hypothermic perfusion and modified oxygenated hypothermic machine perfusion, subnormothermic machine perfusion and machine normothermic perfusion.Results. The daily increase in the number of patients in need of organ transplantation delays the timely selection and search for a donor. Organ donation after cardiac death is a promising step in an attempt to overcome the disbalance between the number of patients and organs, but the risk of developing early graft damage increases. The criteria for selecting donors and donor organs are being expanded, as a result, elderly donors and not-optimal grafts are included, but they are less resistant to ischemic damage. In this connection, there is a need for long-term infusion support through machine perfusion.Conclusion. In recent years, research has focused on alternative preservation methods, studying hypothermic, subnormothermic and normothermic machine perfusion. The use of machine perfusion has become the most widespread among kidney transplants and has shown good results. Further development is expected in the field of studying and improving this method of organ preservation, which allows not only transporting, but also improving the functional state of the graft.

The work is devoted to the analysis of modern literature data and approaches in performing repeated liver transplantation. The most frequent causes of liver graft loss are PNFT, HAT, recurrent initial disease and chronic rejection. The leading indication for retransplantation in children is HAT. The one-year survival rate after retransplantation is approximately 75%. Reducing the cost of organ retransplantation and the cost-effectiveness of the procedure are controversial issues. Mathematical modeling has identified several significant recipient and donor factors affecting the outcomes of retransplantation. Despite ethical and economic considerations, retransplantation is the only option for transplant patients whose grafts have failed to engraft. The decision to retransplant should be made with some caution, with full multi-type approach in large multidisciplinary transplant centers.

Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide, accounting for more than 800,000 deaths annually. Surgical removal of the neoplasm remains the most effective treatment option. Partial liver resection is an adequate solution for patients without cirrhosis or with well-compensated cirrhosis, orthotopic liver transplantation is necessary in patients with early stage HCC on the background of cirrhosis. Tumor recurrence remains a major limitation of long-term survival of patients after liver transplantation. Posttransplant immunosuppression reduces the body's antitumor defense, which is provided by natural immunity. This contributes to the development and progression of the tumor process. Purpose of the study: to analyze domestic and foreign publications that present treatment options for HCC recurrence after liver transplantation. Literature sources were searched in PubMed, Scopus, Web of Science, MEDLINE, eLibrary databases. The search was conducted in Russian and English by keywords: hepatocellular carcinoma, tyrosine kinase inhibitors, immune checkpoint inhibitors, therapy of HCC relapse, orthotopic liver transplantation, RETREAT index, regorafenib, nivolumab. The authors presented a review of the data on the use of tyrosine kinase inhibitors and immune checkpoint inhibitors to prevent HCC recurrence. The results of the analysis of literature sources showed that the issue of post-transplant immunosuppression is relevant. The large number of studies and clinical case reviews leaves hope that an effective way of immunosuppression for recurrent HCC patients after liver transplantation will soon be found.

Introduction. The shortage of donor organs has been and remains the basic problem of clinical transplantation and the expansion of the organ pool by using marginal donor organs has become one of its solutions. In this regard, every decision to use a "non-standard" or "non ideal" organ for transplantation should be made carefully.Aim. Demonstration of successful liver transplantation from a donor with brain death and occlusive thrombosis of the splanchnic venous system.Description. A 34-year-old donor without serious concomitant pathology was diagnosed with total portal thrombosis during liver procurement. After cold aortic perfusion, a thrombectomy from the portal vein was performed. At the “backtable” stage, an additional perfusion was made through the portal vein, the results of which confirmed the patency of the portal system. The liver graft was transplanted to a 33-year-old recipient; the postoperative period was uneventful, the patient was discharged on the 17-th postoperative day.Conclusions. Portal vein thrombosis in a donor liver is rare. A positive decision on liver transplantation from a donor with portal vein thrombosis should be based on the confirmed patency of the portal system. It is desirable that these data be supplemented by a histological examination of the donor liver. The donor organs shortage needs to expand the criteria for post-mortem organ donation. However, every decision should be made in the light of individual characteristics of the donor-recipient pair.

Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.

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.

The article presents the results of liver transplantation in five HIV-infected recipients with irreversible liver damage. It is shown that four of them survived in the long-term period and are observed in a stable condition, and the only death in the recipient was not related to the HIV infection. The experience in the treatment of these patients was summarized. Analysis of the first results of liver transplantation in HIV-infection in Russia shows its validity and clinical efficacy. The only lethal case is connected with the initial extremely grave condition of the recipient and his age. Two cases of surgical traumatism, lack of consistent vaccination in the preoperative period, as well as lack of patients with hepatocellular cancer, small number of observations are obvious drawbacks of our first experience and should be corrected in the future. The success of a complex and multidisciplinary program of organ transplantation in HIV infection is impossible without participation of HIV-infectionists in the transplantation team.

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p

Introduction. Orthotopic liver transplantation is the most radical method of treatment of hepatocellular carcinoma. The high recurrence rate limits the use of transplantation in patients with hepatocellular cancer. Immunosuppressive therapy may affect the frequency of oncoprogression after liver transplantationAim. To evaluate the role of immunosuppressive therapy in the postoperative progression of hepatocellular cancer in patients after liver transplantationMaterial and methods. The recurrence rate of hepatocellular cancer and tumor free survival in 104 patients after liver transplantation were analyzed. To evaluate the effect of the immunosuppression main component concentration on the postoperative progression of hepatocellular carcinoma, we studied the mean baseline concentration (C0) for the entire follow-up period for patients with a tumor-free period and the mean baseline concentration for patients with hepatocellular carcinoma progression, in whom only the duration of the tumor-free period was studied. According to the degree of tumor lesion, patients were distributed in accordance with the Milan criteria (based on the results of a pathologic and morphological examination of the recipient's explanted liver.Results. The values of the baseline blood level of tacrolimus>6.0 ng/ml and cyclosporine A>100 ng/ml is associated with a high rate of progression of hepatocellular cancer. Reducing the load of calcineurin inhibitors can reduce the incidence of cancer progression by at least 2 times. The values of 1-, 3- and 5-year relapse-free survival in patients with advanced cancer and low figures of the baseline blood level of calcineurin inhibitor are 82%, 70% and 70%, respectively.Conclusion. Minimization of immunosuppression is of crucial importance in the prevention of posttransplant progression of hepatocellular cancer, especially among patients with its common form.

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.

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.

Introduction. Liver transplant (LT) is a widely accepted treatment for hepatocellular carcinoma (HCC). The role of neoadjuvant (NAT) is still under debate.The aim of the work is to assess the effect of NAT on relapse-free survival (RFS) and overall survival (OS) in patients with HCC who underwent LT.Methods and materials. 63 patients diagnosed with HCC were observed at Blokhin National Medical Research Center of Oncology from October 2010 to January 2020. Of these, 28 patients did not receive any type of treatment before transplantation, 35 patients received various types of NAT. Two groups had similar patient and tumour characteristics at baseline. A significant number of patients with decompensated cirrhosis were observed in the non-NAT group (n = 14; 50%), while no patients with CP-C liver cirrhosis were observed in the NAT group (n = 0; 0%; p = 0.000). The average wait for a liver transplant was 10.3 months in the NAT group and 6.8 months in the NAT-free group (p = 0.561).Results. In the bridging subgroup, the tumour progression was detected in 29% of patients, stable disease in 47% of patients, partial response was achieved in 14% of patients, complete tumour response was observed in 5%. For 5% of patients, it was not possible to estimate the effect of the therapy due to the lack of appropriate data archives. In the subgroup of downstaging therapy, the tumour progression was detected in 23% of patients, stable disease in 41% of patients, a partial response was achieved in 12% of patients, a complete tumour response was observed in 6%. The treatment allowed the Milan criteria to be fulfilled in 18% of patients.Conclusion. There was no difference in overall survival (OS) or disease-free survival (DFS) between the NAT and control groups.

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.

06.18.2021 in the Samara regional hospital named after I. V.D. Seredavin hosted a conference "Hightech medical care for patients of the Samara region – new horizons", organized by the Ministry of Health of the Samara region, the Samara regional branch of the Interregional public organization "Society of Transplantology", Medical University "Reaviz". The work is a resolution of the conference presidium.

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.

The implementation of the liver transplantation program at Sklifosovsky Institute of Emergency Medicine has a long history. Over the last 20 years, more than 700 patients have received high-tech medical care (transplantation) here.

Coronavirus 2019 (COVID-19) is a severe acute respiratory infection (TORI) caused by the new coronavirus SARS-CoV-2. The SARS-CoV-2 virus is a single-stranded stranded RNA virus with nucleocapside. Sequencing of its complete genome has shown that it is closely related to SARS-CoV, with which it shares about 79 % of its genome. The article describes the pathogenesis of COVID-19 and potential approaches to treating patients as well as approaches to patient management after transplantation with COVID-19.

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 10th day after surgery in satisfactory condition.Conclusion. Situs inversus is not a contraindication to 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.

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. 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.

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

The paper reviews the milestones and prerequisites in the history of the emergence and development of xenotransplantation. The currently existing barriers (immunological, infectious, genetic, ethical, and regulatory) to the development of this organ and tissue transplantation type have been studied. Available data on theoretical research and experimental studies have been reviewed. The prospects for performing xenotransplantation in various combination of species have been assessed. The forms and variants of the xenograft rejection reaction have been described. Genetic engineering approaches to overcoming xenoimmunological incompatibility are described. An assessment is made of ways to overcome existing barriers and prospects for the further development of xenotransplantation as a scientific section of transplantology.

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.

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.

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.

This article is аn example of a successful treatment intra-abdominal infection after liver transplantation.

Abstract. Using a steatotic graft in liver transplantation (LT) can lead to a poor function and high mortality. The role of the rapid liver graft biopsy processing was studied. The liver grafts of potential donors were assessed for hepatic steatosis.Material and methods. The study included 341 cases of cadaveric donor liver transplantations. Patients were divided in two groups: the study group where the rapid graft biopsy processing was performed (n=163) and the comparison group (n=178) without biopsy processing. Livers with macrosteatosis of over 50% of graft parenchyma or with severe necrosis and structural damage were discarded.Results. The rates of ischemic reperfusion injury (IRI), initial poor graft function (IPGF), and primary graft nonfunction (PNF) were significantly lower in the study group. There were no significant differences between two groups in cold ischemia time.Conclusion: rapid histological examination provides a useful tool to avoid life threatening LT complications such as severe IRI, IPGF, and PNF.

Acute traumatic aortic rupture is associated with extremely high mortality rates and requires emergency diagnosis and treatment. This clinical example shows the role of multislice spiral computed tomography in the emergency diagnosis of rupture of two large arterial vessels in severe concomitant injury. It presents the benefits of this rapid and noninvasive imaging technique, an algorithm of the study and the semiotics of injuries in patientswith suspected traumatic aortic rupture. The paper also shows the importance of this method in defining treatment policy and then in the assessment of the results of the performed correction.

This article is an example of a successful treatment invasive fungal infections and bacterial infections caused by multidrug-resistant pathogen after liver transplantation

Authors reviewed published data concerning antiviral treatment of liver transplant recipients with 1st generation HCV protease inhibitors (telaprevir and boceprevir). Efficacy and adverse events have been analyzed with peculiar attention to drug-drug interactions between calcineurin inhibitors and HCV protease inhibitors. The article is illustrated with clinical cases.

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.