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This article is presented in form of a current literature review on bacterial complications of the early post-liver transplantation period and promising areas for studying the effect of bacterial flora in patients after liver transplantation. The paper describes the problem of the emergence, spread, and pathogenesis of various bacterial complications, as well as current concepts of various bacterial complication’s impact on the results of liver transplantation. The results of ventilatorassociated pneumonia in patients after liver transplantation are given. A theoretical analysis of bacterial complications from the standpoint of microbiota effects on the biliary tree was carried out. The review also highlights a relatively new conceptual approach in examining the results of scientific research using the "Machine Learning Method”. The so-called CDC “Big Four” was chosen as the main infectious nomenclature in this article. However, catheter-associated bacterial complications, which pathogenesis has been sufficiently studied to date, have been replaced by a relatively new group of complications – bacteriobilia. This review also contains a brief statistical data collected in the frames of the NCT04281797 study. Own cohort data consisted of 57 patients who underwent orthotopic liver transplantation from a post-mortem donor. Surgical site infection was the most common bacterial complication of the early postoperative period. The most common causative agent of bacterial infection was Klebsiella pneumonia and Enterococcus.

Introduction. Sarcopenia is a common complication of chronic liver disease. Today many studies are devoted to sarcopenia impact on the course of liver diseases. At the same time, many studies are being performed on the correlation of sarcopenia in patients with cirrhosis of the liver and the incidence of early complications after liver transplantation. In this regard, we conducted our own retrospective study of the correlation relationship of sarcopenia in patients with chronic liver diseases.Aim. To determine the correlation between the severity of sarcopenia and the incidence of complications of liver cirrhosis in patients on the waiting list for liver transplantation.Material and methods. In our own retrospective observational study, 87 patients suffering from chronic liver diseases and treated at the Minsk Scientific and Practical Center of Surgery, Transplantation and Hematology were included. The assessment of sarcopenia was carried out using the CT technique for assessing indexed parameters of the patient's muscle mass. Mathematical processing was performed using the FDA-approved OsirixTM software. The study was conducted within the framework of the project "ClinicalTrials: NCT04281797"Results. Body mass index was significantly correlated with the presence of sarcopenia (rpb=-0.48, 95% CI [-0.65;-0.27]). At the same time, the groups of patients with and without sarcopenia differed significantly (p

This paper reviews modern literature and presents a brief analysis of our own data on one of the most pressing issues in modern transplantology and, in particular, transplant hepatology – the role and place of gut-liver axis (GLA) in the early post-transplant period. Objective: to compare the correlation between gut microbiome palette and incidence of certain early postoperative complications in liver transplantation. Materials and methods. The study design is presented as a pilot, prospective, observational, double-blind study based on investigation of the composition of the microbiome residing in the large intestinal in patients that underwent orthotopic liver transplantation (OLTx). The primary cohort of patients consisted of 12 patients who underwent OLTx from a postmortem donor. To assess the gut microbiome palette, biomaterial was collected from all patients in the preand post-transplant period followed by next-generation sequencing. The study was conducted as primary study results registered under number NCT04281797. Results. In the preoperative period, differences close to statistically reliable in relation to Actinobacteria were observed in patients included in the liver transplant waiting list for cirrhosis (LC) and hepatocellular carcinoma (HCC) in cirrhosis. However, due to the pilot nature of the study, this study cohort was limited to an extremely small sample. In turn, in the post-transplant period, there was a statistically significant difference in the taxonomic range of Actinobacteria (p < 0.05) between the above groups, indicating a possible effect of liver transplantation on the gut microbiome. In addition, in the early post-transplant period, there was a marked difference in the microbiome palette between patients with and without acute cellular rejection. Conclusion. GLA and the gut microbiome play a critical role in many liver diseases, and may also have a significant impact on the post-transplant period. In this regard, further research in this direction will not only characterize the predictors and risk factors of bacterial infection and rejection episodes, but will also allow us to form a completely new approach to the treatment tactics for certain complications, including through formation of a microbiota-oriented pharmacotherapy.

Placentoid transformation (in English publications – placental transmogrification) extremely rare lung disease, characterized by formation of villous structures, which look like chorionic villus with pulmonary emphysema. We report the first case of 28 y. o. patient with giant placentoid transformation and chronic obstructive pulmonary disease. We used extracorporeal membrane oxygenation support for surgical management and it let the oxygen-dependent patient to return to normal life.

The paper presents the world’s first clinical case of two full-term successive pregnancies in a patient following simultaneous liver-kidney transplantation with reno-portal transposition. Both pregnancies ended with the birth of healthy children and favorable course of postpartum and long-term periods. The features of management and childbirth are highlighted. Literature review on this problem is presented.

Introduction. Accurate blood pressure (BP) measurements are the mainstay for the efficient management of abrupt changes of hemodynamics and perfusion during orthotopic liver transplantation (OLT).Material and methods. The prospective study included 39 patients. We compared the BP values measured in the femoral and radial arteries during the different phases of the OLT.Results. The central systolic arterial pressure (SAP) and mean arterial pressure (MAP) measured invasive in the femoral artery were significantly higher than those measured in the peripheral artery during the anhepatic phase (95.1±10.6 vs. 84.5±9.9 mm Hg, and 66±8.8 vs. 59.7±7.1 mm Hg, respectively), after 5 minutes of reperfusion (91.1±17.3 vs. 78.5±18.4 mm Hg, and 63.9±13.1 vs. 57.7±13.6 mm Hg, respectively), and after 15 minutes of reperfusion (102.2±16.8 vs. 88.1±14.4 mm Hg, and 67.7±10.7 vs. 62.5±10.4 mm Hg, respectively). We found a strong correlation between the differences of SAP and MAP and the dose of norepinephrine administered during the anhepatic phase (r=0.76 and r=0.77 for SAP and MAP, respectively), and after 5 minutes of reperfusion (r=0.71 and r=0.52 for SAP and MAP, respectively). The difference between central and peripheral BPs after 15 minutes of reperfusion mainly depended on the changes in the potassium concentration (r=0.55 for SAP and MAP) and base deficiency (r=0.73 and r=0.82 for SAP and MAP, respectively).Conclusion. Thus, it was proved that the invasive measurement of BP in the femoral artery is a more accurate method compared with that in the radial artery as it is less exposed to high doses of vasopressors and variations in the acid-base state during OLT.

Introduction. Diagnosis of the kidney transplant cellular rejection in the long-term after transplantation remains a challenge. Usual surrogate markers are not enough sensitive and specific. Rejection is an immune reaction to donor alloantigens. The kidney transplant biopsy to diagnose a dysfunction is an invasive procedure with the incidence of complications about 12.6% and can lead to transplant loss. In this regard, the search of immunological biomarkers for early noninvasive and accurate diagnosis of kidney transplant rejection is an actual task.Material and methods. This is a report of the observational retrospective single-center, comparative case-control study in two groups involving 44 patients who underwent kidney transplantation. The first group (REJ) included the patients with the chronic graft dysfunction caused by a biopsy-confirmed late cellular rejection (22 patients). The second group (STA) included the recipients who had no dysfunction in the posttransplant period (22 patients). Flow cytometry of peripheral blood cells was performed to identify immunophenotyping markers of late cellular rejection after kidney transplantation (we determined subpopulations of T, B lymphocytes, and dendritic cells).Results. As a result of our work, we found significant differences in the absolute count of effector memory T cells making 0.147 (0.115–0.260) × 109 cell/L in REJ group, and 0.106 (0.067–0.136) × 109 cell/L in STA group (р = 0.0167). Relative and absolute counts of myeloid dendritic cells were also different between the groups: 0.65 (0.36–0.73) vs. 1.05 (0.67–1.4) % and 0.039 (0.028–0.056) vs. 0.063 (0.049–0.076) × 109 cell/L, respectively (р = 0.0009, р = 0.003). The numbers of plasmacytoid dendritic cells were also different between the study groups: 0.0038 (0.0021–0.0054) vs. 0.005 (0.0035–0.007) × 109 cell/L for an absolute count (р = 0.0414), and 0.055 (0.04–0.085) vs. 0.09 (0.05–0.12) % for a relative count (р = 0.0197).Conclusion. The obtained data showed that the blood level of dendritic cells, which are the main “professional” initiators of immune reaction, and the level of effector helper T memory cells, which constitute the main lymphocyte subpopulation posing a destructive impact on the kidney transplant, can be considered as diagnostic markers of kidney transplant cellular rejection in the long-term after surgery.

The paper shows the main stages of introduction and organization of liver transplantation in the Republic of Belarus, the procedure of examination of patients on the waiting list for liver transplantation, and the experience of the first 37 orthotopic liver transplantations made in the Republic of Belarus in April 3, 2008, to February 1, 2010.

The article is dedicated to the problem of pregnancy management and delivery after simultaneous liver-kidney transplantation (SLKT). The article contains general historic and statistic information, and presents the first real world clinical case of favorable pregnancy outcome in patient after simultaneous liver-kidney transplantation with reno-portal transposition.

Despite the fact that the key role of the liver in the formation of the immune response to injury is not in doubt, the mechanisms of weakening the immune response to infectious and noninfectious lesions in patients with hepatic failure remain unclear. We propose an original hypothesis of forming the ways to limit the amplitude of the systemic inflammatory response in patients with the end-stage liver disease. The basis of the hypothesis is the idea that as a result of reducing the intensity of the natural stimulation of membrane mCD14 receptors by the ligands of infectious nature, the basic mechanism of the systemic immune response induction by liver macrophages (Kupffer cells) is interrupted. According to the proposed hypothesis, in condition of liver failure, the synthesis of lipopolysaccharide-binding protein by hepatocytes is reduced. This leads to a decreased amplitude and intensity of the protective immune responses. This fact explains a number of clinical phenomena observed in patients with liver failure/dysfunction that consist in a reduced reactivity of the organism to the damage inflicted by infectious and noninfectious agents. The authors consider it possible to use this hypothesis in the search for new trends to prevent the immune system hyper-reactivity in sepsis, and to improve the therapeutic strategies for the management of patients at high risk of infectious complications after liver transplantation.

Ligation of the inferior vena cava (IVC) during classical orthotopic liver transplantation (OLT) may be followed by pronounced hemodynamic changes and may provoke renal dysfunction. The authors have examined the impact of IVC ligation during OLT without venovenous bypass grafting on early postoperative renal function in 6 patients. The Cockcroft-Gault formula was used to evaluate renal function from the creatinine clearance on postoperative days 1, 3, 7, and 10. The endogenous creatinine clearance was diminished within the first 24 hours after surgery; this was 68.2±18.1 (24.3—146) ml/min and significantly correlated with that before OLT, with the mean blood pressure (BPmean) in the icteric period, and with age. At the same time, icteric BPmean was in the normal range — 77.2±1.59 (71.6—81.6) mm Hg and clinical renal failure developed in a female patient with significant preoperative renal dysfunction. Thus, IVC ligation at OLT with IVC interposition in the study contributed to a lower endogenous creatinine clearance within the first 24 postoperative hours, but results in no clinical renal function aggravation.

Aim. To evaluate the associations of genotypes of clinically relevant nucleotides rs11536865, rs913930 and rs5030717 of the TLR-4 gene with the risk of development and severity of early allograft dysfunction after liver transplantation. Materials and methods. A case-control study enrolling 71 patients was organized. Inclusion criteria: DBD liver transplantation. Exclusion criteria: living related liver transplantation, reduced graft transplantation, recipient’s age fewer than 18. Results. Within rs5030717 there were identifi ed three genotypes: AA (81.6%) and two genotypes with the minor G-allele: AG (12.6%) and GG (5.6%). Within rs913930 there identi- fi ed three genotypes: TT (59.1%) and two genotypes with the minor C-allele: C/T (29.5%) and CC (11.2%). The rs11536865 studying revealed no polymorphism (GG genotype). The early allograft liver dysfunction (EAD) developed in 19.7% of patients, the severe EAD in 11.2% of patients, septic complications in 14%, acute cellular rejection in 23.9% of cases. The C/T genotype of the TLR-4 gene in the SNP rs913930 sequence was closely associated with the EAD development (OR 4.8 to 1; p = 0.047; 95% CI 1–23.4). Рatients with the donor’s liver C/T genotype had a reliably higher proportion (%) of the HMGB1 positive hepatocytes in the donor’s bioptate, 21 (17–29%) vs the СС+TT genotypes, 16 (10–19%) (Mann–Whitney test, p = 0.01). The CD68 expression in the liver bioptate at the donor’s stage was reliably higher in the carriers of heterozygotes in the SNP rs913930 (C/T genotype) and in the SNP rs5030717 (AG genotype), (Mann–Whitney test, p = 0.03). Signifi cant positive correlation between the CD68 expression in the donor’s liver bioptates and the IL-23 level in the hepatic vein has been determined in an hour after the portal reperfusion (ρ = 0.62; p = 0.04) as well as between the HMGB1 expression in the donor’s liver bioptates and the АSТ level in 24 hours after the reperfusion (r = 0.4; p = 0.02). The HMGB1 staining in the donor’s liver bioptates was higher in the EAD patients, 21 (20; 29) cells/mm2 in comparison with the patients without EAD, 16 (12; 18) (Mann–Whitney test, p = 0.0036). Conclusion. The early allograft liver dysfunction is associated with the genetic predisposition caused by the TLR-4 gene polymorphism and is implemented via the HMGB1, Kupffer cells and IL-23 activation.

Major surgical procedures induce a number of pathophysiological responses, which may lead to a significant increase in perioperative complications, delayed recovery and rehabilitation, and longer hospital stays. Fast-track surgery, also known as enhanced recovery after surgery (ERAS) or as multimodal surgery, aims at decreasing the frequency of postoperative complications, creating optimal conditions for earlier postoperative recovery and return to normal life activities.The implementation of fast-track programs results in a reduced treatment duration without increase in readmissions. In this article, we have described our experience in the application of fast track program components to improve the outcomes after liver transplantation.

It was shown that Tacrolimus (Tac) can suppress infl ammation and immune response involved in liver ischemia-reperfusion injury (IRI) (Kristo I., Transpl Int., 2011). Aim. We hypothesize that back-table arterial and portal liver perfusion with Tac can infl uence the incidence and severity of early allograft dysfunction (EAD). A prospective randomized study was conducted (ClinicalTrials.gov Identifi er: NCT01887171).Materials and methods. Criteria of the inclusion: First liver transplantation from DBD donor with sequential portal-arterial reperfusion. At back-table portal vein and hepatic artery were perfused each by 500 ml of HTK solution containing 20 ng/ml Tac during 10–15 min followed by portal fl ushing with 200 ml 5% solution of Albumin containing 20 ng/ml Tac and by resting of liver in effl uent. No Tac was added in the control group. Primary Outcome: EAD (Olthoff KM, et al. Liver Transpl. 2010) and severe EAD (P.R.Salvalaggio, et al. Transpl. Proceedings, 2012).Results. No difference was found between groups (main vs. control) in terms of MELD (16 vs. 16), steatosis (10 vs. 10%), ballooning (45 vs. 40%) of liver grafts, recipient age (50 vs. 50 y.o.), warm ischemia time (50 vs.50 min) and total ischemia time (482.5 vs. 485.0 min). Median donor age was higher in the main group (44.5 vs. 39.0 y.o.). The overall rate of EAD was 27.9%. EAD rate was signifi cantly lower in the main group (6/43 vs. 18/43; p = 0.003). The rate of moderate-to-severe EAD was lower in the main group (1/43 vs. 10/43; p = 0.009). The median levels of AST and ALT in 24 h after reperfusion were signifi cantly lower in the intervention group (1004 vs. 1596; p = 0.03 and 449 vs. 759; p = 0.057).Conclusion. Portal and arterial back-table liver perfusion with HTK solution with Tacrolimus may contribute to lower EAD incidence and severity.

Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury.

Central pontine myelinolysis (CPM) is the rare, but extremely severe complication after orthotopic liver trans- plantation. The reason for CPM is currently not precisely defined. However, the rapid correction of hyponatremia is considered as the main etiological factor. In this paper we present two clinical cases of CPM in patients under- went orthotopic liver transplantation. We also discuss the pathophysiology, epidemiology, clinical presentation, treatment options and preventive measures of CPM.

The liver is an essential player in the pathway of coagulation in both primary and secondary hemostasis as it is the site of synthesis of all coagulation factors and their inhibitors. Liver diseases are associated with complex changes in coagulation and the delicate balance between pro and antithrombotic factors is preserved but reset to a lower level. There is growing evidence that portal and hepatic vein thrombosis is cause of disease progression in cirrhotic patients and worsens hemostatic abnormalities. These hemostatic abnormalities do not always lead to spontaneous bleeding, which may be triggered only by additional factors, such as infections. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. In patients with end stage liver disease liver transplantation is the only treatment available, which can restore normal hemostasis, and correct genetic clotting defects. During liver transplantation hemorrhage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis.