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Russian Journal of Transplantology and Artificial Organs

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Vol 27, No 2 (2025)
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Editorial

Clinical Transplantology

8-22 26
Abstract

Objective: to analyze a clinical case series and evaluate the safety and efficacy of a sequential machine perfusion protocol combining dual hypothermic oxygenated perfusion (D-HOPE) and normothermic machine perfusion (NMP) for conditioning and viability assessment of liver grafts retrieved from expanded criteria donors (ECD) in routine clinical practice.

Materials and methods. Between November and December 2024, two sessions of combined D-HOPE followed by NMP were conducted at Shumakov National Medical Research Center of Transplantology and Artificial Organs («Shumakov Research Center») using liver allografts obtained from ECD after brain death. Following an initial period of static cold storage (SCS), machine perfusion was initiated using a circulatory assist device. A histidine-tryptophan-ketoglutarate (HTK)-based perfusate was used during the DHOPE phase, while a red blood cell (RBC) suspension was used during the NMP stage. Throughout perfusion, temperature and hemodynamic parameters were continuously monitored and maintained. Laboratory parameters were assessed at designated intervals, in accordance with the institutional protocol developed at Shumakov Research Center.

Results. Allograft #1 was deemed non-viable due to elevated lactate levels after 3 hours of perfusion and lack of glucose metabolism. The preservation times were as follows: SCS – 424 minutes, D-HOPE – 120 minutes, NMP – 300 minutes, totaling 844 minutes. Allograft #2 met the viability criteria and was successfully transplanted. Preservation times were: SCS – 260 minutes, D-HOPE – 124 minutes, NMP – 480 minutes, with a total preservation time of 884 minutes. Post-transplant peak levels of AST, ALT, and total bilirubin in the recipient were 922.5 U/L, 613 U/L, and 63.3 μmol/L, respectively. The only postoperative complication was acute kidney injury, managed with two sessions of hemodialysis. The patient was discharged after 14 days of hospitalization without need for readmission. At the time of writing, the patient is alive and complication-free, with a follow-up period of 3 months.

Conclusions. Combined machine perfusion of liver grafts appears to be a safe and effective strategy to mitigate ischemia-reperfusion and preservation-related injury in liver transplantation. It also facilitates viability assessment of marginal liver grafts, reduces potential recipient complications, and expands the donor pool through the use of allografts from ECD.

23-30 20
Abstract

Treatment and kidney transplantation (KT) for patients with autosomal dominant polycystic kidney disease (ADPKD) are associated with increased risks, particularly due to the potential for infection of polycystic kidney (PK) cysts. Currently, no standardized guidelines exist for the surgical management and pre-transplant preparation of these patients.

Objective: to analyze the 15-year experience at a transplant center managing KT recipients with end-stage chronic kidney disease (eCKD) due to ADPKD.

Materials and methods. A retrospec- tive and prospective analysis was conducted on 132 ADPKD patients who underwent staged surgical treatment between 2008 and 2023. In the first stage, outcomes of 155 PK nephrectomies performed via laparoscopic and open approaches were evaluated. In the second stage, KT outcomes were assessed in 63 ADPKD recipients, com- paring those with preserved native kidneys to those who had undergone nephrectomy. Additionally, as a control group, KT outcomes in 129 patients with eCKD of other etiologies from 2013 to 2023 were analyzed.

Results. The study revealed significant advantages of laparoscopic access for PK nephrectomy, including a shorter length of stay in both intensive care and the hospital, as well as a lower complication rate (47.8% for laparotomy and lumbotomy approaches, and 12.8% for laparoscopic access). However, patients who underwent KT with preser- ved PK exhibited a higher incidence of infectious complications (26.9%), primarily due to cyst infections and resistance to standard antibiotic prophylaxis. Long-term graft survival was notably lower in this group, with a ten-year survival rate of 46.2%, compared to 73.1% in patients who had undergone nephrectomy and 74.1% in the comparison group.

Conclusion. The integration of laparoscopic surgery for polycystic kidney disease into clinical practice has the potential to significantly reduce surgical complications and broaden the indications for PK nephrectomy. Among ADPKD patients who underwent nephrectomy, the post-transplant period was more favorable, with outcomes comparable to those of KT recipients with eCKD of other etiologies.

31-38 22
Abstract

Objective: to enhance liver transplant (LT) outcomes by developing and implementing intraoperative fluorescence imaging of common bile duct (CBD) blood supply using indocyanine green (ICG).

Material and methods. The study analyzed treatment outcomes in 203 recipients who received a whole liver from deceased donors. In the first stage, the incidence and potential risk factors of biliary complications were assessed in Group I, comprising 138 patients. The median follow-up period was 35.6 months (IQR: 25–68 months). Group II consisted of 65 cases, with a median follow-up of 7.2 months (IQR: 6.5–13). In this group, intraoperative ICG fluorescence imaging was employed to assess CBD blood supply. Following cholecystectomy, a 5 mL intravenous injection of ICG solution (2.5 mg/mL) was administered. Near-infrared fluorescence imaging was then performed by overlaying near-infrared light onto white light to visualize ICG fluorescence in CBD tissues. In cases where fluorescence imaging indicated hypoperfusion of the distal part of the graft’s CBD, the affected segment was excised within the boundaries of well-perfused tissue. In all cases, the resected CBD portions were sent for histological exami- nation.

Results. In Group I, biliary anastomosis complications were recorded in 13 out of 138 cases (9.4%), all of which were strictures. Analysis of potential risk factors on both the recipient and donor sides did not reveal any statistically significant associations (p > 0.05). Comparison of intraoperative fluorescence imaging results with postoperative histological examination demonstrated a sensitivity of 87% and a specificity of 92% for detecting ischemic changes in CBD. In groups with comparable baseline characteristics (p > 0.05), the incidence of biliary anastomotic strictures (BAS) was significantly lower in the ICG imaging group: 9.4% in Group I versus 1.5% in Group II (p = 0.04).

Conclusion. The use of fluorescence imaging to assess the blood supply of the CBD in LT is an effective method for preventing biliary complications. This technique enables the formation of biliary anastomosis within a well-perfused tissue, significantly reducing the risk of BAS.

39-45 35
Abstract

Introduction. Living-donor liver transplantation (LT) is a viable and effective treatment option for patients with end-stage liver disease. Cachexia is widely recognized in medical literature as a risk factor affecting patient sur vival after LT. However, there are relatively few reports on LT in adult patients with critically low body weight.

Materials and methods. The clinical case of successful LT in a critically underweight patient (BMI 12.9 kg/m2) is presented.

Results. The patient’s pre-transplant preparation included intensified enteral and parenteral nutrition, albumin and fresh frozen plasma transfusions, diuretic therapy, multivitamins, symptomatic treatment, and structured exercise. At the time of transplantation, the recipient’s MELD (Model for End-Stage Liver Disease) score was 22. In the postoperative period, the patient had multiple complications, reflected by a comprehensive complication index (Comprehensive Comprehensive) score of 99. Multicomponent rehabilitation was implemented. The patient was discharged 30 days after LT. During a 17-month follow-up, graft function remained satisfactory.

Conclusion. Our experience, supported by literature data, indicates that cachexia in liver transplant recipients is associated with a higher overall complication rate after LT. Patients with low body weight require careful pre-transplant preparation, including intensive nutritional support and exercise programs. Successful treatment of such patients is feasible only in a multidisciplinary hospital or a transplant center with extensive expertise in managing complex cases.

46-53 29
Abstract

Introduction. Kidney transplantation (KT) is often considered the best option for renal replacement therapy (RRT), significantly improving patient outcomes. Post-transplant, life expectancy doubles, and mortality decreases more than 4-fold compared to other RRT modalities. This article presents KT outcomes in Irkutsk Region from 2018 to 2023. All procedures were performed at a single center – the Irkutsk Regional Clinical Hospital.

Objective: to analyze the immediate and long-term outcomes of KT in Irkutsk Region.

Material and methods. A retrospective analysis was conducted on the treatment outcomes of 125 patients with kidney failure (KF). Among them, 74 were men with a median age of 42 (35–49) years, and 51 were women with a median age of 46 (37–55) years. The median transplant waitlist time was 15.5 (range: 6–32) months. The leading cause of KF was chronic glomerulonephritis, observed in 60 patients (48%). There were no HLA matches in 36 patients (28.8%), while 38 patients (30.4%) had one match. Arterial anastomosis was primarily performed end-to-end with the external iliac artery in 121 cases (96.8%), while in 3 cases (2.4%), the internal iliac artery was used due to external iliac artery spasm. Cold ischemia time was 222 minutes (range: 162–360), and warm ischemia time was 39 minutes (range: 30–46).

Results. Length of hospital stay was 16 (range: 13–25) bed days. Primary renal function was achieved in 95 patients (77%), while 25 patients (20%) experienced delayed graft function. Blood tacrolimus reached target levels by postoperative days 9–12. Creatinine level at discharge was 120 μmol/L (range: 97–165). Surgical complications occurred in 24 patients (19.2%), while urinary tract infections were observed in 36 patients (28.8%), with 17 cases (13.6%) presenting clinical symptoms. Immunosuppressive therapy was initiated in 124 patients (99.2%) using a standard triple-drug regimen (calcineurin inhibitors, mycophenolates, and glucocorticoids). One patient (0.8%) succumbed to complications from COVID-19. One-year graft survival was 94.1%.

Conclusion. The immediate outcomes align with national averages. There is a consistent upward trend in the number of kidney transplants performed. Further development of the regional transplant program will enhance access to this high-tech medical service, meeting the needs of the local population.

54-59 16
Abstract

Objective: drawing on existing literature and the clinical use of radiopharmaceutical (RFP) 18F-FMISO in on- cology, this pilot study aims to assess the feasibility of using non-invasive PET-CT imaging to detect hypoxia in liver grafts resulting from ischemia-reperfusion injury.

Materials and methods. 18F-FMISO uptake in tumors, as visualized by PET-CT, enables the generation of quantitative maps of tissue hypoxia, a technique that is increa- singly being explored to guide radiation therapy planning. As part of refining the study methodology, the research team successfully obtained the first PET-CT images demonstrating 18F-FMISO uptake in the liver of a patient at a late postoperative stage following liver transplantation.

Results. A positive indication of transplant hypoxia was defined as an increase in both the mean and maximum standardized uptake values (SUVs) when measured at 180 minutes post-intravenous injection of the radiopharmaceutical, compared to measurements at 90 minutes. Two imaging series – CT and PET – were acquired. Diffuse uptake of the radiopharmaceutical was observed in the liver, with greater tracer retention relative to background at 180 minutes compared to 90 minutes post-injection.

Conclusion. The findings suggest the presence of transplant hypoxia despite the absence of biochemical abnor- malities. This technique shows promise as a non-invasive diagnostic tool for detecting hypoxic changes in liver grafts. However, further optimization and validation of the technique are necessary.

Heart Transplantation and Assisted Circulation

60-68 15
Abstract

The Fontan procedure is a surgical technique used for hemodynamic correction of complex congenital heart defects (CHDs), and is used when radical correction of CHDs is anatomically impossible. In the long term – from 10 to 20 years – Fontan circulation can lead to «failing Fontan» characterized by heart failure symptoms, requiring adjustments to medical treatment and potentially surgical interventions, including heart transplantation (HT). Foreign studies indicate that HT is an effective method for prolonging life in patients with failing Fontan circulation. It stabilizes the patient’s condition. This paper presents the first documented case of HT in a child following a Fontan procedure in the Russian Federation.

69-80 21
Abstract

Objective: to analyze the impact of MHC mismatches, considering recipient nationality and age, on the develop- ment of rejection crisis.

Material and methods. A retrospective study was conducted, including 264 recipients and their 264 matched donors. HLA typing was performed by serological and molecular genetic (SSP) methods. Mismatches in the following MHC class I and II genes were assessed: HLA-A, HLA-B, HLA-DRB1, HLA- DQB1. Recipient age and nationality were also considered in the analysis.

Results. MHC Class I mismatches (HLA-A, HLA-B) did not significantly impact the occurrence of acute rejection crises. MHC Class II mismatches (HLA-DRB1, HLA-DQB1) significantly increased the risk of acute rejection (χ2 = 6.790; df = 1; p = 0.009), with an odds ratio (OR) of 5.69 (95% CI: 1.32–24.50). Recipient age had a significant effect on acute rejection (χ2 = 8.200; df = 1; p = 0.004). Recipients under 45 years experienced rejection in 34.8% of cases, 18.9% more than those aged 45 and older, with an OR of 2.30 (95% CI: 1.29–4.10). Donor-recipient nationality mismatch signifi- cantly influenced acute rejection (χ2 = 4.660; df = 1; p = 0.031), with an OR of 2.00 (95% CI: 1.06–3.79). The analysis, considering all three above-mentioned factors, confirmed that MHC mismatches significantly influence the development of acute graft rejection in Belarusian recipients under 45 years old (χ2 = 4.068; df = 1; p = 0.044) and in recipients of other nationalities (Russians, Israelis, Georgians, Armenians, Uzbeks, Kazakhs, Azerbaijanis, Ukrainians) under 45 years old (χ2 = 4.342; df = 1; p = 0.037). Among Belarusian recipients, no cases of rejec- tion were observed with 0–1 MHC mismatches, while rejection occurred in 35.4% of cases with 2–4 mismatches (OR 9.44, CI 0.51–173.61). Similarly, in recipients of other nationalities, acute rejection did not develop with 0–1 mismatches, but occurred in 50.0% of cases with 2–4 mismatches (OR 11.00, CI 0.56–217.69).

Conclusion. It has been reliably established that MHC class II mismatches, donor-recipient nationality differences, and recipient age under 45 years significantly increase the risk of acute rejection crisis in the postoperative period.

81-88 15
Abstract

Objective: to conduct bench tests and determine the working range of the pump speed for an implanted left ven- tricular bypass system aimed at diagnosing and treating patients with low anthropometric status.

Materials and methods. The axial pump was investigated using a custom-developed hydrodynamic test bench simulating the cardiovascular system. The bench included systems for pressure and flow measurement and registration, along with software for processing both technical and biomedical parameters.

Results. The operating range of the rotor speed for the STREAM CARDIO pump required to achieve a flow rate of 2.5 ± 0.5 L/min at a pressure drop of 80 ± 5 mm Hg is 8000 ± 1000 rpm, with a power consumption of 6.5 ± 1 W.

89-99 26
Abstract

Objective: to examine the historical evolution, current advancements, and future prospects of long-term mecha nical circulatory support (LT-MCS) devices in the management of end-stage heart failure.

Materials and methods. An analysis was conducted on clinical studies (MOMENTUM 3, INTERMACS, EUROMACS), historical records, and technological progress in the field of LT-MCS. The review covered three generations of devices: pulsatile pumps (first generation), axial-flow pumps (second generation), and centrifugal pumps with magnetic levitation (third generation). Key outcomes evaluated included survival rates, complication rates (thrombosis, infections, right ventricular failure), and developments within national technology.

Results. The HeartMate III third-generation device has a 2-year survival rate of 82% with a pump thrombosis risk of less than 1%. However, complications remain, including driveline infections (10–15%), right ventricular failure (20–40%), and bleeding events (15–20%). Domestic systems (Stream Cardio) are comparable to second-generation devices but lag in terms of miniaturization and clinical trials. Emerging technologies like the Leviticus FiVAD wireless energy transfer system and the Carmat Aeson fully implantable artificial heart are opening up promising new directions for the future of mechanical circulatory support.

Conclusion. Modern LT-MCS systems have emerged as a via- ble alternative to heart transplantation (HT), particularly for patients who are not candidates for HT. Key areas of ongoing development include device miniaturization, wireless energy transfer technologies, and integration of artificial intelligence. The future of LT-MCS will largely depend on overcoming current system limitations, notably the risks of infection and right ventricular failure.

Regenerative Medicine and Cell Technologies

100-111 20
Abstract

Objective: to investigate the biodegradation of natural silk-based tissue scaffolds (NS-TS) under in vitro and in vivo conditions, assessing their potential for tissue engineering applications.

Materials and methods. Two types of NS-TS, Fibroplen-Atlas and Fibroplen-Gas, along with their modified versions, were analyzed. In vitro biodegradation was assessed in Fenton’s solution, while in vivo studies were conducted on rats, with histological and morphometric analysis of the implants at 4, 14, and 56 days post-implantation.

Results. In vitro biodegrada- tion studies showed that Fibroplen-Gas completely degraded in <15 days, whereas Fibroplen-Atlas persisted for up to 45 days. In vivo analysis showed gradual resorption of all scaffolds, with Fibroplen-Gas exhibiting more pronounced degradation. Histological examination revealed a macrophage response, formation of foreign-body giant cells, and signs of implant vascularization. Morphometry confirmed a reduction in filament cross-sectional area, particularly in modified samples.

Conclusion. Modifications of NS-TS influence their biodegradation rate, inflammatory response, and vascularization.

112-126 30
Abstract

Bone defect repair is an interdisciplinary research field encompassing surgical orthopedics, regenerative medici- ne, tissue engineering, immunology (addressing biocompatibility challenges), materials science and technology (including additive manufacturing, porosity, and mechanical strength), and nanotechnology for developing bio- compatible matrices that enhance bone regeneration. This literature review highlights recent advancements in bone tissue engineering, focusing on the application of autologous biomaterials in combination with biocompatible matrices to improve bone regeneration outcomes.

127-138 24
Abstract

Currently, there are no highly effective small-diameter (≤4 mm) grafts on the market for cardiovascular surgery. Tissue-engineered, functionally active vascular grafts with prolonged resorption and regeneration capacity have the potential to serve as alternatives to traditional arterial grafts. These bioengineered grafts could eliminate the need for repeated surgical interventions to replace failed grafts. The accuracy of assessing the risks of failure in biodegradable small-diameter vascular grafts (SDVGs) during preclinical trials is highly dependent on the choice of animal model. This article presents the results of comprehensive preclinical trials conducted on an SDVG developed at the Research Institute for Complex Issues of Cardiovascular Diseases. Based on these findings, the study evaluates the effectiveness and feasibility of different animal models for testing biodegradable SDVGs.

139-147 16
Abstract

Current research focuses on exploring strategies to stimulate the regenerative capacity of pancreatic beta cells as a potential therapeutic approach for diabetes mellitus (DM).

Objective: this study aims to perform a comparative histological analysis of the islet apparatus in rats with streptozotocin (STZ)-induced DM following the implantation  of a pancreatic cell-engineered construct (PCEC). The PCEC consists of isolated allogeneic islets of Langerhans embedded within a scaffold derived from decellularized human pancreatic fragments.

Materials and methods. The pancreases of rats from the control group (n = 4; untreated type 1 DM – T1DM), experimental group 1 (n = 4; intraperitoneal injection of pancreatic islets), and experimental group 2 (n = 4; intraperitoneal injection of PCEC) underwent histological analysis. Immunohistochemical staining for insulin and glucagon was performed using specific antibodies and an imaging system.

Results. In the pancreatic islets of the control group, insulin- immunopositive beta cells were either absent or detected as isolated cells, with alpha cells predominating. In the pancreases of experimental group 1 rats, beta cells were observed in most islets and within the surrounding exocrine parenchyma, albeit in low numbers (1–2 per field of view), while alpha cells remained the dominant population. A significant increase in insulin-positive cells was observed in the pancreas of rats in experimental group 2, along with a reduction in glucagon-positive cell numbers.

Conclusion. Morphological examination of the pancreatic islet apparatus in the experimental animals revealed that implantation of the PCEC had a be- neficial effect on restoration of the recipient’s pool of functionally active beta cells, serving as a trigger for the regenerative process.

148-162 43
Abstract

Despite advancements in modern reconstructive surgery, preventing the formation of thick scar tissue that impairs limb function or causes cosmetic defects remains a critical challenge. Equally important is the effective correction of existing scars to optimize both functional and aesthetic outcomes. Severe functional impairment of the upper limbs can result in disability. A combination of surgical and nonsurgical interventions is essential to enhance functionality while minimizing the risk of scar recurrence. Platelet-rich plasma injections, stem cell therapy, adipose tissue transplantation, and a combination of negative pressure wound therapy (NPWT) with traditional flap reconstruction and other transplantation methods are gaining popularity in modern reconstructive surgery. NPWT plays a crucial role in preparing the wound bed for subsequent tissue reconstruction and serves as an effective alternative to traditional dressings. The vacuum created over the wound after closure with a skin autograft helps prevent inflammation at the graft base, reduces excessive granulation tissue formation, and minimizes the risk of rough scar development in the long term. The mechanisms of formation of hypertrophic scar and keloids have not yet been completely understood. However, research indicates that bone marrow-derived cells, including fibrocytes and keratinocyte-like cells, contribute to the inflammatory cell infiltrate during wound healing, and can play a role in cutaneous fibrosis, especially in cases of impaired healing. Several pathophysiological and biochemical processes involved in the repair of extensive and deep wounds have been established. Additionally, the role of keratinocytes within hair follicle bulbs in promoting epithelialization of post-burn wound surfaces, particularly in areas with preserved skin appendages, has been recognized. Studies indicate that stromal-vascular fraction of adipose tissue plays a positive role in various stages of wound healing, including keloid and hypertrophic scar formation. Adipose-derived stem cells can be used in combination with hydrogel. The hydrogel base of dressings maintains a moist environment in both burn wounds and wound surfaces following tangential or radical excision of burn scab. This promotes faster wound healing, reduces the risk of scar hyperplasia, and enhances the sustained release and effectiveness of medications applied to the hydrogel base. Prompt surgical intervention, including early excision and grafting, along with modern treatment methods in the early postoperative period for deep burns, can significantly reduce the risk of hypertrophic and keloid scar formation.

163-170 20
Abstract

Objective: to investigate the regulatory effects of exogenous lymphocyte RNA on thyroid gland regeneration.

Materials and methods. The study was conducted on 18 male Wistar rats (310–350 g), divided into three groups (n = 6 per group). Group 1 – intact rats; group 2 – control rats (subjected to 6 weeks of physical activity), group 3 – experimental rats (subjected to 6 weeks of physical activity + RNA injection). Total RNA, isolated from the spleen of a 30-day-old pig, was administered four times at a dose of 30 μg/100 g body weight, once per week. Follicular epithelium and vascular structures were analyzed using morphometry, VEGF content was quantified via immunohistochemistry with specific antibodies, and thyroid microvascular function was assessed using laser flowmetry.

Results. Following RNA administration, the relative thyroid gland mass increased by 16%, the folli- cular epithelium area expanded 1.5-fold, and the vasculature area doubled. Additionally, VEGF content increased 2.5-fold compared to intact rats, while microcirculation intensity rose by 64%, and vascular resistance decrea- sed by 21%.

Conclusion. Administration of morphogenetically active total RNA under conditions of increased oxygen demand promotes regenerative hypertrophy of the glandular epithelium and enhances microcirculation in the thyroid gland.

Transplantomics

171-178 14
Abstract

Recent advances in molecular diagnostics have opened new avenues for integrating genetic and epigenetic bio- markers into clinical practice. Areas such as gene expression profiling, extracellular DNA quantification, and microRNA expression analysis have seen significant development in recent years. The diagnostic value of mo- lecular genetic biomarkers has been demonstrated across a range of pathological conditions. Emerging clinical data now support the use of molecular diagnostics to detect post-transplant complications in recipients of solid organ transplants. In heart transplant recipients, a comprehensive assessment that includes molecular genetics, epigenetic, and clinical parameters is essential for personalized selection of immunosuppressive therapy and for prevention of graft dysfunction and vasculopathy. This review highlights the current state of molecular diagnostics in cardiac allograft rejection and explores its potential for clinical application.

179-188 13
Abstract

Objective: to investigate the association between plasma TGF-β1 levels in pediatric liver transplant (LT) recipients, both preand post-transplantation, and the polymorphic alleles and haplotypes at rs1800469 and rs1800470 loci of the TGFB1 gene.

Materials and methods. The study cohort comprised 135 pediatric LT recipients, aged 3 to 98.4 months (mean age 8.2 years, median 8 months). The control group consisted of 77 healthy individuals, aged 30.3 ± 5.2 years. Plasma TGF-β1 levels were quantified using ELISA. Genomic DNA from participants was analyzed for the polymorphic loci rs1800469 and rs1800470 of the TGFB1 gene using real-time polymerase chain reaction PCR with TaqMan probes.

Results. Blood TGF-β1 level in pediatric LT recipients pre-transplant was 4.6 (1.1–9.5) ng/mL. One month post-transplant, cytokine level increased to 6.3 (1.7–15.0) ng/mL (p = 0.008), and after one year, it rose further to 7.0 (1.9–13.5) ng/mL (p = 0.0001). Healthy adults had significantly higher TGF-β1 levels, with a median of 11.7 (6.4–16.9) ng/mL (p = 0.0000), compared to pediatric recipients. The distribution frequencies of the rs1800469 and rs1800470 polymorphic alleles in pediatric LT recipients did not significantly differ from those in healthy individuals. However, the occurrence of rare haplotypes (T-T and C-C) was significantly higher in pediatric recipients. Before transplantation and 1 month after the procedure, TGF-β1 levels in pediatric recipients were not associated with the carriage of the studied alleles or haplotypes. However, at 1-year post-transplant, higher TGF-β1 levels in pediatric recipients were significantly associated with the major alleles (C/C + C/T) of rs1800469 and the rs1800470 T/T genotype, as well as with the T-T haplotype. In healthy individuals, TGF-β1 levels were not influenced by the rs1800469 and rs1800470 alleles individually, but high cytokine levels were associated with the C-C haplotype.

Conclusion. In pediatric LT recipients, elevated TGF-β1 levels at 1-year post-transplant are associated with the presence of the major alleles C (rs1800469) and T (rs1800470), as well as the T-T haplotype of the TGFB1 gene. This suggests that these polymorphic loci may influence the development of post-transplant complications and could potentially serve as biomarkers for predicting clinical outcomes in LT.

Literature Reviews

189-211 20
Abstract

Despite significant advancements in the field of liver transplantation (LT) over the last 30 years, the gold standard for allograft preservation – static cold storage with pharmacological agents – has remained largely unchanged. The growing disparity between demand for liver transplants and shortage of donor livers, along with a high wai ting list mortality rate (potentially up to 20%), has forced transplant teams to broaden donor eligibility criteria. This expansion, however, has inevitably impacted both the immediate and long-term LT outcomes. Dynamiс preservation of liver allografts has shown consistently positive outcomes, particularly among expanded criteria donors, including those classified as high-risk donors» Over the past decade, several perfusion techniques, tegrating various temperature conditions, have been developed and are under active investigation. A significant advancement in this area is the emergence of combined sequential ex vivo machine perfusion, which integrates multiple perfusion strategies. This approach leverages the strengths of each method while mitigating their in- dividual limitations. This paper reviews current experience with combined sequential ex vivo perfusion of liver grafts, providing a concise overview of the key stages encompassed within this protocol.

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