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Background. Liver transplantation remains a priority treatment option for hepatocellular carcinoma in the presence of liver cirrhosis; yet precise outcome prediction post-operation continues to be a complex challenge. Existing prognostic model often overlook patient age and donor type. Enhanced models that incorporate these parameters can improve prediction accuracy and treatment efficacy, which is critically important in the dynamically evolving field of transplantation.Objective. The aim of this study is to develop a prognostic model for liver transplantation outcomes in patients with hepatocellular carcinoma and liver cirrhosis.Material and methods. This retrospective study included 69 patients with hepatocellular carcinoma on the background of liver cirrhosis who underwent liver transplantation between May 2010 and December 2022. Of these, 42 patients (61%) received organs from living donors, and 27 (39%) from deceased donors. The study involved analysis of alpha-fetoprotein levels in blood, as well as assessment of radiological (maximum tumor nodule size, number of nodules) and histological parameters (maximum tumor nodule size, number of nodules, presence of vascular invasion). Cox regression model was used to predict recurrence-free survival, and the results for five-year recurrence-free survival, recipient age, and donor type were reused in the Cox model to predict overall survival.Results. Four models for predicting recurrence-free survival and overall survival based on histological and radiological data were developed, demonstrating high prognostic value with C-indexes on training/test data of 0.76/1; 0.73/1; 0.78/0.8; 0.6/0.8 respectively. All models showed recurrence-free survival prediction accuracy comparable to the Milan criteria. The model outcomes are available as a calculator on the website https://nadit.ru/calculate_HCC.Conclusion. The developed prognostic models are vital tools for personalized outcome prediction after liver transplantation for hepatocellular carcinoma. To enhance the accuracy of these models, further amalgamation and validation of data from various medical centers, as well as open scientific collaboration, are necessary.

Rationale. The risk of early graft loss determines the specifics and plan of anesthesiological assistance, intensive therapy, and overall the feasibility of liver transplantation. Various prognostic models and criteria have become widespread abroad; however, Russian transplant centers have not yet validated them.Objective. To evaluate the applicability and accuracy of the most common models predicting the risks of early adverse outcomes in liver transplantation from deceased donors.Material and methods. A retrospective single-center study included data on 131 liver transplantations from deceased donors performed between May 2012 and January 2023. For each observation, DRI, SOFT, D-MELD, BAR, MEAF, L-GrAFT, and EASE indices were calculated, and compliance with an early allograft dysfunction criteria was verified. Depending on the possibility of calculating the indicators and their values relative to known cutoff points, the study groups were formed, and 1-, 3-, 6-, and 12-month graft survival rates were calculated. The forecast was compared with the actual outcomes, and sensitivity, specificity, F1-score, and C-index were calculated.Results. When assessing the risk of 1- and 3-month graft loss, models using only preoperative parameters demonstrated relatively low prognostic significance: DRI (F1-score: 0.16; C-index: 0.54), SOFT (F1-score: 0.42; C-index: 0.64), D-MELD (F1-score: 0.30; C-index: 0.58), and BAR (F1-score: 0.23; C-index: 0.57). Postoperative indices of MEAF (F1- score: 0.44; C-index: 0.74) and L-GrAFT (F1-score: 0.32; C-index: 0.65) were applicable in 96%, those of ABC (F1-score: 0.29; C-index: 0.71) in 91%, and EASE (F1-score: 0.26; C-index: 0.80) in 89% of cases. The relative risk of 30-days graft loss in case of EAD was 5.2 (95% CI: 3.4-8.1; p

Rationale. The refinement of liver transplantation technique, the development and implementation of new surgical technologies into clinical practice, including those for inferior vena cava reconstruction, are important for the improvement of surgery outcomes.The study purposes were to present our own modification of cavocavostomy and options for its technical implementation in deceased donor liver transplantation, as well as to study the clinical effects and the impact of new surgical technique on the outcomes.Material and methods. A retrospective, single-centre study included the data from 109 consecutive deceased donor liver transplantations performed between 2012 and 2021. In 106 procedures, inferior vena cava reconstruction was performed either according to the classic technique (group 1, n=23, 22%), or using our own modification of cavocavostomy (group 2, n=83, 78%). To assess the clinical efficacy and safety of the new surgical technique, we compared the characteristics of donors and recipients, intraoperative parameters, features of early postoperative course, incidence of surgical complications, initial function, immediate and long-term graft survival. Three piggyback procedures were not included in the comparative analysis.Results. Two groups were generally comparable in terms of the characteristics of donors and recipients, however, the classic inferior vena cava was significantly more often used during transplants for unresectable parasitic liver lesions (17% vs. 1%, p=0.008) and retransplantations (30% vs. 5%, p=0.002). There were no statistically significant differences in the main intraoperative parameters between groups 1 and 2. The duration of transplantations was 8.0 h (interquartile range: 6.5–8.5 h) and 7.0 h (interquartile range: 6.0–8.0 h), p=0.112; anhepatic phase lasted 70 min (interquartile range: 60–75 min) and 70 min (interquartile range: 59–90 min), p=0.386; warm ischemia time was 45 min (interquartile range: 38–52 min) and 45 min (interquartile range: 38–50 min), p=0.690; inferior vena cava was clamped for 47 min (interquartile range: 40–55 min) and 50 min (interquartile range: 40–55 min), p=0.532. The volumes of intraoperatively transfused blood components were, respectively: packed red cells 630 ml (interquartile range: 0–1280 ml) and 600 ml (interquartile range: 0–910 ml), p=0.262; blood reinfusion 770 ml (interquartile range: 360–1200 ml) and 700 ml (interquartile range: 0–1200 ml), p=0.370; fresh frozen plasma 2670 ml (interquartile range: 2200 and 3200 ml) and 2240 ml (interquartile range: 1880–2900 ml), p=0.087.When using classic caval reconstruction technique, the proportion of grafts with early dysfunction was higher: 44% vs. 17% (p=0.011), due to the higher rate of retransplantations in this group. The incidence of acute kidney injury (by RIFLE > I) was 35% and 19% (p=0.158), the need for renal replacement therapy was 22% and 15% (p=0.520) in group 1 and group 2, respectively. The total incidence of surgical complications in the early postoperative period was 30% and 16%, p=0.110.Conclusions. The proposed technique of cavocavostomy can be considered as a priority method for caval reconstruction during deceased donor liver transplantation, with the exception of specific indications for the use of the classic technique (retransplantation, involvement of the inferior vena cava wall in a parasitic process or presentation of a tumor node to it, as well as in cases of widespread adhesive process in the abdominal cavity, hypertrophy of the 1 segment of the native liver, the presence and location of TIPS, thinning of the wall of the retrohepatic inferior vena cava, the risk of graft compression with its large size).The choice of the cavocavostomy variant should be carried out taking into account the size ratio of the graft to the recipient's right subdiaphragmatic space, and the topography features of the recipient's hepatic veins.

Background. The novel coronavirus infection (COVID-19) pandemic has had a significant impact on all areas of health care system, including organ donation and transplantation. Despite this, there were no large Russian studies of COVID-19 course and outcomes in liver transplant recipients.The study purpose was to determine prevalence, clinical course, severity, outcomes of COVID-19, as well as to assess the safety and efficiency of vaccination for disease prevention in liver transplant recipients.Material and methods. 260 recipients (71% of all patients at risk of COVID-19 disease) who underwent liver transplantation at State Research Center – Burnasyan Federal Medical Biophysical Center from May 2010 to September 2021 were included in a single-center cross-sectional study. Data collection was performed during a telephone or face-to-face interview from September 6, 2021 to September 20, 2021. If patients were hospitalized with COVID-19, we also analyzed the results of laboratory and instrumental tests, other medical documentation.Results. By mid-September 2021, the incidence of COVID-19 after liver transplantation was 31% (75 cases in 260 recipients). Asymptomatic course was observed in 11 (15%) patients. Hospitalization was required in 18 (28%) cases. In one case, COVID-19 infection was the cause of death. Mortality and death rate in the study cohort were 1% (1/75) and 0.4% (1/260), respectively. Risk factors that statistically significantly increased the likelihood of infection with SARS-CoV-2 were contact with the patient (OR: 12.9; 95% CI: 6.6 - 25.0) and non-compliance with non-specific prophylaxis measures (OR: 2.0; 95 % CI: 1.1 - 3.7). The recipient's age of 60 years or more significantly increased the risk of severe infection (OR 5.0; 95% CI: 1.3 - 18.7). None of the immunosuppressive therapy regimens significantly increased the risk of severe disease. Tacrolimus monotherapy or in combination with other drugs reduced the risk of severe COVID-19 (OR: 0.2; 95% CI: 0.1 - 0.95). Vaccination against SARS-CoV-2, which was performed in 42 (17%) recipients, did not cause serious adverse events and significantly reduced the risk of COVID-19 disease (OR: 7.2; 95% CI: 1.7 - 31.3). The detection rate of specific IgG antibodies to SARS-CoV-2 was 94% in recipients who had undergone the disease and 45% among those vaccinated (p

The aim was to study the results of using various treatment regimens for hepatic encephalopathy for patients with liver cirrhosis before and after liver transplantation and the effect on the incidence and severity of hepatic encephalopathy in the perioperative period, and on the posttransplantation course.Material and methods. Fifty four patients with cirrhosis of various etiologies and the presence of significant hepatic encephalopathy undergoing living donor liver transplantation were included in the study. In the comparison group, patients took lactulose and rifaximin. In the main group, patients took lactulose and rifaximin in combination with L-ornithine-L-aspartate in the preoperative period, and L-ornithine-L-aspartate after liver transplantation for 5 days.Results. The use of L-ornithine-L-aspartate in the complex therapy of hepatic encephalopathy led to significantly reduced time of performing the Number Connection Test, the improvement of cognitive functions in patients by the Montreal Cognitive Assessment, a decreased incidence of stage II–III hepatic encephalopathy and an increased incidence of stage 0-I hepatic encephalopathy in the preoperative period. In the postoperative period, patients of the main group showed a rapid decrease in the severe stages of hepatic encephalopathy (stage II–III) towards less severe forms (stage 0–I) on the 3rd, 5th and 7th days after liver transplantation, and also a faster recovery of cognitive functions, an earlier adequate recovery of consciousness, muscle tone, an earlier possibility of extubation, a shorter length of stay in the intensive care unit, and a decreased postoperative hospital length of stay relatively to the patients of the comparison group.Conclusion. The use of L-ornithine-L-aspartate in the combination therapy for hepatic encephalopathy in the peritransplantation period leads to a significant decrease of the incidence and severity of hepatic encephalopathy, accelerates rehabilitation of patients, reduces postoperative hospital length of stay.

Rationale. Currently, a long-distance transportation of the deceased donor livers is not a routine practice for Russian transplantation centers; therefore, a research-based analysis of even relatively small single-center experience seems to be a topical task.The study purpose was to evaluate the impact of long-distance donor liver transportation on the cold ischemia time, the initial graft function as well as on immediate and long-term transplant outcomes.Material and methods. The retrospective single-center study included the data on specific features and results of 72 consecutive deceased donor liver transplantations. The cases were allocated into two groups depending on cold ischemia time: for less than 9 hours (group 1; n = 41) and for 9 hours or longer (group 2; n = 31). The parameters of donor organ transportation, characteristics of donors and recipients, specific features of surgery and the early postoperative period, immediate and long-term outcomes were compared between the groups. For the entire sample size, the relationship between the distance from the donor hospital to the transplant center, the transportation type and time, and the cold ischemia time were assessed.Results. Donor livers were delivered from hospitals 40-3500 km away from the transplant center, including by using regular air flights in 67% of cases. Transportation time varied from 1 to 8 h (median 3.5 h), which made 41% (interquartile range: 35-54%) of cold ischemia time.No statistically significant differences between the groups were seen in the donor, recipient and surgery characteristics. The median distance was 509 km in group 1 (interquartile range 130-1321 km), and 1321 in group 2 (interquartile range 897-3441 km), p

Rationale: The imbalance between the need for donor organs and their current availability is a growing problem for all countries. An assessment of potential donor numbers is considered to be an important step towards better understanding of the problem as a whole at the national scale. This would help to build up a concept of a successful strategy to resolve this inequity.Aim: To analyze the use of external audit of the efficacy of identification of potential organ donors with confirmed brain death.Materials and methods: As a part of a pilot project aimed to increase the efficacy of donor bases of the Russian Federal Medical Biological Agency (FMBA), we retrospectively analyzed 5932 medical files of patients who died from 2014 to 2018 in the departments of resuscitation and intensive care units of 26 medical establishments serving as a donor bases in Moscow, Orenburg, Saratov, Abakan, Stavropol and FMBA of Russia. The probability of brain death was assessed with a special QAPDD (Quality Assurance Program in the Deceased Donation Process) technique focused on organ donation after brain death which is used for external audit in Spanish hospitals.Results: Clinical manifestation of brain death were identified in 20.3% (95% confidence interval (CI) 18.4–22.4) of the patients aged 18 to 65 years with severe primary and secondary brain injury who died in the departments of resuscitation and had been maintained on mechanical ventilation at least 12 hours until their death was confirmed. The rate of potential donor identification with clinical manifestations of brain death in the donating in-patient departments was 12% (95% CI 10.5–13.7) of those who died with severe primary and secondary brain injury. The external audit performed in 26 donating in-patient departments, has shown that 41% (95% CI 35.8–46.4) of potential donors with brain death were not identified.Conclusion: With the use of the QAPDD technique in our study, we found that 41% of potential donors were not identified in the Russian in-patient clinics participating in organ donation. Based on the information obtained during the audit of medical files in intensive care units, we can make realistic conclusions on the current system of organ donation, identify potential pitfalls in the identification procedures of potential donors, increase the efficacy of donation process, and to improve the system as a whole. The process could become effective only through the activities of specially trained donor hospital transplant coordinators.

Background. Cancer occurring in recipients of living donor liver transplantation may be characterized by a progressive course requiring an immediate specialized treatment initiation and adjustment of immunosuppression regimen. Aim. To specify the malignancy development mechanisms and risk factors in the recipients of living donor liver transplantation. Material and methods: 275 living donor liver transplantations were made in Burnasyan Federal Medical Biophysical Center of FMBA from 2010 to 2020. Forty two (15.27 %) patients underwent surgery for hepatocellular carcinoma. The median time to the onset of malignancy development was estimated. The incidence of malignancy in general population and in recipients of living donor liver transplantation was compared. Results. The development of neoplastic lesion was registered in 9 cases (3.27%). Malignances were detected in 8 cases (2.90%). Median time to the onset of malignancy development was 48 months. 1, 3, and 5 year overall survival rates were 97%, 96%, 94%;respectively; 1, 3, and 5 year survival rates after transplantation for hepatocellular cancer were 97%, 91%, 91% respectively. Survival rate of patients with De-novo malignancy was 90%. Conclusion. Recipients of living donor liver transplantation have an increased risk of malignancy development that requires a close long-term follow-up.

Assessing the viability and monitoring the function of liver graft in the early postoperative period are critical clinical tasks. One possible solution is to determine the changes in concentration of blood glucose, its metabolites and glycerol in the graft using interstitial microdialysis. Objective: to study the dynamics of interstitial glucose, lactate, pyruvate and glycerol in the early post-liver transplant period – depending on the initial graft function (IGF) – and to compare with the results of standard laboratory blood tests. Materials and methods. Four selected clinical observations of deceased donor liver transplantation are presented. Two of the observations showed normal IGF, one observation – early allograft dysfunction (EAD), complicated by hepatic artery thrombosis (HAT), while one observation demonstrated primary non-function (PNF). Collection of microdialysis samples began after arterial reperfusion of the liver graft and continued continuously for 7 days or until death. Standard blood biochemistry and coagulation tests were performed at least once a day. Results. With normal IGF and a smooth postoperative period, interstitial concentrations of glucose, lactate, pyruvate and glycerol remained stable throughout the observation period, ranging from 5 to 20 mmol/L, 1.1 to 7.5 mmol/L, 90 to 380 μmol/L, and 10–100 μmol/L, respectively. EAD was associated with initially higher levels of glucose, lactate, and pyruvate. With HAT development, there was a rapid (within 2–4 hours) five-fold increase in interstitial concentration of lactate with simultaneous decrease in glucose and pyruvate levels to 0.1 mmol/L and 11 μmol/L, respectively. In the case of PNF, there was an initially high concentration of interstitial lactate – 16.4 mmol/L, which increased further to 35.5 mmol/L. Glucose concentration was close to 0. Changes in interstitial glucose, its metabolites and glycerol concentrations chronologically preceded the corresponding changes in peripheral blood composition by 3–5 hours. Conclusion. Microdialysis measurement of interstitial glucose, lactate, pyruvate and glycerol concentrations facilitates real-time monitoring of liver graft viability and function. The high sensitivity of the method could help in accelerating diagnosis of vascular complications (HAT in particular), as well as graft dysfunction with other causes. Therefore, the method is feasible in clinical practice.

On February 7, 2019, a one-day Consensus Conference of the International Liver Transplantation Society was held to discuss oncology issues. Representatives of world's leading clinics gathered in Rotterdam (Netherlands). The presentations made on that day covered the following topics: hepatocellular cancer, bile duct cancer, immunotherapy and its place in the treatment of liver tumors, the possibility of liver transplantation in patients with metastatic liver disease, world trends in pediatric oncohepatology. A separate session in the working groups was allocated to discuss the most actual topics. The Conference identified the main global trends and the most crucial issues in the field of liver transplantation in patients with oncological diagnosis. It is likely that these presentations will “set the tone” for the large Transplantationt Congress in Toronto in May 2019.

Rationale: Adult-to-adult right lobe living donor liver transplantation is a viable alternative to whole liver transplantation from a deceased donor. The key aspect of the surgical procedure is the restoration of adequate graft blood flow and maintenance of sufficient volume of well vascularized parenchyma in the donor. Specific features of vascular anatomy in the donor and the recipient can be eventual cause for significant technical difficulties during transplantation. They can also increase the risk of complications and deteriorate graft functioning.Aim: To identify the incidence of various types of afferent and efferent vascularization of right lobe of the liver, potential techniques of vascular reconstructive procedures, rates and types of postoperative complications, as well as immediate surgical results.Materials and methods: We retrospectively analyzed the data on 220 right lobe liver transplantations adult patients, consecutively performed from 2010 to 2017 in one center. Specific characteristics of liver vascularization in donors and recipients were determined by pre-operative computed tomography and intra-operatively. The information on the types of vascular reconstruction, complications and results of surgical procedures was obtained from patients' medical files.Results: The following variants of blood supply to the right liver lobe were seen most frequently: portal vein trifurcation 22%, shortened trunk of the right portal vein branch 13%, supplementary v. hepatica from SgVIII with a diameter of > 5 mm 22%, supplementary lower right v. hepatica 17%, isolated venous outflow from all right lobe segments 2%, two arteries 2%. In addition, 17% of the recipients had portal vein thrombosis and 1% portal vein fibrosis. During the follow-up all donors remained alive. The rate of surgical complications was 12.5%, among them bile pocket or biloma 8.5%, intra-abdominal bleeding 2.5%, wound complications 1.5%. The rate of early post-operative complications in the recipients was 31.5%, with 4.5% of them being vascular and 15.5% biliary. The 6-months and 4-years survival of the recipients (Kaplan-Meier) was 98% and 95%, respectively.Conclusion: Immediate and longterm survival of the recipients of living donor right lobe live grafts, as well as absence of fatalities among their donors, confirm high effectiveness and expedience of this type of intervention. The observed anatomic variety of blood supply to the right liver lobe stipulates stringent requirements to the quality of preoperative diagnostics, deliberate donor selection, thorough planning of the procedure and high qualification of the surgical team. A relatively high rate of postoperative complications warrants the necessity of an intensive diagnostic monitoring in the early post-operative period and active strategies of their correction.

Rationale. There have been only single studies conducted in the Russian Federation to characterize the posthumous donor population.Objective: Identifying the main characteristics of the donor pool in N.V. Sklifosovsky Research Institute for Emergency Medicine of Moscow Healthcare Department and in the State Research Center – A.I. Burnasyan Federal Medical Biophysical Center, FMBA, for the period from 2008–2017.Material and methods. The clinical records of 429 actual and effective posthumous donors were analyzed retrospectively. The following characteristics were studied: gender, age, permanent place of residence, cause of death, the duration of mechanical lung ventilation, type of donation, total number of harvested organs, and number of organs recovered per donor.Results. There were 281 male and 148 female donors. The increase in the mean age of donors from 37 to 48.5 years was noted. Cerebrovascular disease and traumatic brain injury became the main causes of death. Since 2012, the rate of cerebrovascular diseases as the cause of donor death has increased from 30% to 70%. Of 429 actual donors, the brain death was diagnosed in 366 (85.3%). Four hundred eight deceased became effective donors. A total of 1,247 donor organs (744 kidneys, 220 livers, 42 pancreas, 2 intestines, 180 hearts, 58 lungs, and 1 facial vascularized composite allograft) were obtained. The mean number of donor organs recovered per donor was 3.06.Conclusions. The results obtained can be used to develop unified protocols and results of posthumous donors and to assess the possible volume of transplant care. In the period 2008–2017 an increase in the average age of posthumous donors (from 38.1 to 48.7 years) due to the proportion of donors in the 18–29 age group (from 29 to 4%) and an increase in the proportion of donors in the age group over 60 (from 3 to 15%). From 2012 to 2017 (from 68 to 29%) due to an increase in the number of donors who died as a result of cerebrovascular diseases (from 30 to 71%). Among the posthumous donors delivered by ambulance teams directly to the intensive care units, 69% of the consciousness level was depressed to 5 and lower on the Glasgow coma scale.

Hemophagocytic Syndrome (hemophagocytic lymphohistiocytosis, macrophage activation syndrome) is a rare form of systemic inflammatory response. It usually presents with nonspecific symptoms like fever, lymphoadenopathy, hepatosplenomegaly, cytopenia. Secondary hemophagocytic syndrome is usually associated with severe infection. We describe a clinical case of a patient after liver transplantation who developed hemophagocytic syndrome secondary to Epstein-Barr virus and Human Herpes virus Type 8. There had been 22 cases of hemophagocytic syndrome after liver transplantation described in literature by the moment of our observation. We found just 1 similar case of a patient suffered from hemophagocytic syndrome in combination with Kaposi sarcoma and Epstein Barr virus infection. Differential diagnostics of hemophagocytic syndrome is difficult as there are no specific symptoms. Rapid disease progression makes early diagnosis and treatment an actual problem.