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Transplantologiya. The Russian Journal of Transplantation

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Vol 16, No 4 (2024)
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EDITORIAL

ACTUAL ISSUES OF TRANSPLANTATION

400-411 531
Abstract

Background. A safe removal of the liver right lobe and restoration of arterial blood supply to the liver graft is possible only with a full understanding of the anatomy of the hepatic artery in a donor.

Objective. To describe new and extend contemporary data on anatomical variations of the arterial blood flow in a donor of the right liver lobe.

Material and methods. From 2009 to 2021, 306 living donor liver transplantations were performed in the State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The vascular anatomy of 518 potential donors was analyzed. Hepatic artery anatomical variants of a right lobe graft were assessed.

Results. Eleven types of right lobe arterial supply and 7 subtypes of the arterial anatomy of liver segment 4 were identified. The case rates of types and subtypes where reconstruction could be performed were following: type A, subtypes 1, 2, 3, 4, 5 (57.5%, 26.1%, 5.5%, 1.9%, 0.3%, respectively); type B, subtypes 1, 4, 5 (0.3% each); type С, subtypes 1, 2 (2.9%, 1.3%, respectively); type D, subtypes 1, 3 (0.3% each); type Е subtype 1 (0.6%), types F-J subtype 1 (0.3% each). Liver right lobe harvesting and arterial reconstructions were fully performed in all types and subtypes excluding anatomical type K, subtype 7. Arterial postoperative complications (11 cases) were detected in 3.5% observed cases of 306 transplants and in 5.9% of all patients with complications (184). Mortality rate due to arterial complications was 1.9% (6 cases).

Conclusion. The existing classification of right liver graft hepatic artery anatomy was updated and detailed regarding the applicability in right lobe liver transplant. The arterial anatomy of right lobe liver graft shows great variability and complexity for systematization and thus may need further studies.

412-421 426
Abstract

Background. After successful cardiopulmonary resuscitation for intraoperative cardiac arrest, most patients die in the Intensive Care Unit from multiple organ failure, cardiovascular complications that develop after hypoxic-ischemic damage to the central nervous system. In some patients whose heart is still beating in conditions of mechanical ventilation, a complete and irreversible cessation of all brain functions may occur, that is, brain death.

Objective. Based on clinical criteria, we made an attempt to assess the likelihood of developing a condition consistent with the diagnosis of brain death in those who sustained cardiac arrest during surgery or other medical manipulation and underwent successful cardiopulmonary resuscitation, but died later in the Intensive Care Unit.

Material and methods. A retrospective analysis of medical records related to 45 clinical cases was performed to assess the likelihood of brain death according to the Quality Assurance Programme in the Deceased Donation Process (QAPDD) methodology, which has been used during an external audit in hospitals of Spain and specifically focused on the donation process after brain death.

Results. In 30 (66.7%) patients, based on the proposed criteria, a high probability of developing brain death was noted. At the same time, in 27 (90%) cases, clinical signs of brain death were noted within the first 6 days after cardiopulmonary resuscitation. Biological death in these patients was ascertained within 1 to 119 days from the moment of the development of clinical signs of brain death.

Inference. The concept of brain death has serious medical, economic, legal, and ethical implications. When clinical suspicion of brain death arises, it is important that all such undergo standard diagnostic procedures to objectively rule out or confirm the diagnosis of brain death.

Conclusion. The probability brain death occurrence in patients after intraoperative cardiac arrest and successful cardiopulmonary resuscitation is statistically siqnificant at 66.7% (p=0.0196).

422-437 405
Abstract

Introduction. Reperfusion syndrome has been proven to impact the early results of simultaneous pancreas and kidney transplantation. The optimal values of hemodynamic parameters at the moment of reperfusion of the kidney graft and the pancreas graft have been the subject of discussion in relation to possible early complications and outcomes of simultaneous pancreas and kidney transplantation. This issue needs additional research.

The objective was to evaluate how the intraoperative hemodynamic parameters may influence early results of simultaneous pancreas and kidney transplantation.

Material and methods. The retrospective study was conducted to analyze the impact of intraoperative hemodynamic parameters on the early results of treatment in 83 patients who underwent simultaneous pancreas and kidney transplantation in the N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2008 to 2023.

Given the primary ROC analysis results, we allocated the patients into 2 groups, according to their mean arterial pressure (MAP) values at reperfusion. Group I consisted of patients with MAP<90 mmHg (n=21), group II included patients with MAP>90 mmHg (n=62). The characteristics of donors and recipients were comparable between the groups (p>0.05). The intraoperative hemodynamic parameters of the recipients (MAP, central venosus pressure, heart rate) were analyzed at the beginning of surgery, at reperfusion stages, at the time of making the interintestinal anastomosis, and on surgery completion; the incidence of postoperative complications was studied; the primary functions of the kidney and pancreas grafts were evaluated; the in-hospital graft and recipient survival rates were calculated.

Results. The median values of MAP (mm Hg) were significantly lower in group I compared to those in group II at all stages of surgery, except for the surgery beginning: 87 (86;87) mmHg versus 101 (97;104) mmHg at the time of the kidney graft reperfusion; 89 (83;95) mmHg versus 97 (93;102) mmHg at the time of the pancreatic graft reperfusion; 91 (85;95) mmHg versus 97 (89;99) mmHg at the time of making interintestinal anastomosis; 90 (82;100) mmHg and 103 (90;116) mmHg on surgery completion, respectively (p<0.05). The remaining hemodynamic parameters had no statistically significant differences between the groups (p>0.05). There were no statistically significant differences between the groups in the incidence of postoperative complications, either (p>0.05). The rate of primary kidney graft function was significantly higher in group II (96.8%; n=60) compared to group I (42.9%; n=11) (p<0.05). All recipients displayed a primary pancreatic graft function. The median hospital length of stay in group I days was statistically significantly longer compared to that of the patients in group II, making 45 (28.5;72) versus 34.5 (25;60) days, respectively (p<0.05).

The hospital survival rates of kidney grafts, pancreas grafts and recipients were significantly higher in patients of group II compared to those in patients of group I: 93.5% (n=58), 87.1% (n=54), and 96.8% (n=60) versus 57.1% (n=12), 57.1% (n=12), and 66.7% (n=14), respectively (p<0.05).

Conclusion. MAP 90 mmHg at the timepoint of reperfusion is a factor that has a statistically significant effect on the primary function of a kidney graft in the early postoperative period, associates with the increase in hospital survival rates of grafts and recipients at early stages after simultaneous pancreas and kidney transplantation.

438-446 305
Abstract

Objective. The study objective was to investigate the dynamics of opthalmological complications in the non-diabetic end-stage chronic kidney disease in patients after kidney transplantation.

Material and methods. A long-term observation was conducted to assess the changes in morphofunctional parameters of eyes in patients of the study group (after kidney transplantation, n=135 (269 eyes)) and the comparison group (continued on hemodialysis, n=81 (162 eyes)) over 18 months. Both general and specialized ophthalmological investigation methods were employed.

Results. The observation showed a positive trend in patients after kidney transplantation, which was manifested by reduced corneal and conjunctival calcification. In the comparison group, both an increase and decrease in qualitative signs of retinopathy were seen as based on optical coherence tomography data, while in the study group, most retinopathy signs decreased, indicating a positive trend possibly brought about by the kidney transplantation. Analysis of optical coherence tomography quantitative parameters showed an improvement in central choroidal thickness and retinal nerve fiber layer thickness in the study group.

Conclusion. Kidney transplantation in patients with the non-diabetic end-stage chronic kidney disease leads to a reduction in ophthalmological complications both in the anterior eye segment (reduced corneal and conjunctival calcification) and in its posterior segment (improved optical coherence tomography retinal parameters).

447-457 332
Abstract

Background. The main mechanism underlying the progression of chronic liver transplant disease is an increase in fibrosis, which is associated with an increase in liver density. An effective antiviral therapy for recurrent hepatitis C has led to the increased graft and recipient survival rates.

Objective. To study the long-term effect of successful antiviral therapy on changes in the graft fibrosis stage in liver transplant recipients with recurrent hepatitis C.

Material and methods. Transient elastography was used to study the change in liver density in 33 liver transplant recipients with recurrent hepatitis C before the start of antiviral therapy and 54 months (IQR: 37;59) after its completion. The median liver densities before antiviral therapy and at the end of follow–up were 7.8 kPa (IQR: 6.1;12.0), and 6.4 kPa, respectively (IQR: 5.5;7.7; p<0.0001). Upon completion of the follow–up, the fibrosis stage decreased by 2 in 4 (12.1%) recipients, by 1 in 8 (24.2%) recipients. In 19 (57.6%) cases, the stage of fibrosis did not change, and in 2 (6.1%) recipients it increased by 1. No clear correlations were found between any of the following parameters: alanine aminotransferase activity, gamma-glutamyltranspeptidase activity, body mass index and the liver density assessed before the start of antiviral therapy and on follow-up completion.

Conclusion. Effective antiviral therapy leads to a long-term (over 4-5 years) decrease in liver density, which is largely due to the slowdown and reverse progression of liver fibrosis. The effect of non-HCV-related risk factors on liver density in this patient population is not significant.

PROBLEMATIC ASPECTS

458-472 561
Abstract

Introduction. The analysis of free circulating DNA (cfDNA) holds promise for molecular diagnostics, but its fragmentation and low concentration can complicate PCR analysis.

Objective. To investigate the effect of target length on the amplification efficiency of Y-chromosome markers from cfDNA.

Material and methods. Fifty cfDNA samples were obtained from 39 patients: patients after liver transplantation (n=19), patients with acute leukemia after allogeneic hematopoietic stem cell transplantation (n=10), and pregnant women (n=10). In addition, we prepared 16 chimeric samples by sequential dilution of male cfDNA into female cfDNA from healthy donors. We determined the proportion of male cfDNA using the Y-chromosome marker S02, which is 211 bp in length as suggested by M. Alizadeh et al. We also modified Alizadeh's primer design to obtain a DNA target with a length of 138 bp. The proportion of male cfDNA was also determined by fragment analysis using the amelogenin Y marker (84 bp) from the COrDIS Plus kit (Gordiz LLC, Russia).

Results. In the three groups of patients, amplification of male cfDNA was more efficient when shorter DNA targets were used (p<0.05). In artificially created ‘chimeras’ with a known ratio of male to female cfDNA, analysis of a marker of 84 bp in length gave values closest to the real ones.

Conclusions. In the quantitative models tested so far, shorter PCR targets are preferred for the analysis of cfDNA.

CASE REPORTS

473-482 224
Abstract

Background. Benign recurrent intrahepatic cholestasis is a rare inherited disorder characterized by recurrent episodes of severe hyperbilirubinemia and pruritus that resolve spontaneously. However, attacks of cholestasis may persist for several months and in some cases be associated with frequent recurrences, which may be grounds for liver transplantation.

Objective. To present a clinical case of debut benign recurrent intrahepatic cholestasis following acute hepatitis A.

Results. A 30-year-old patient was admitted at the Liver Transplantation Center of Moscow Regional Research and Clinical Institute n.a. M.F. Vladimirskiy for a prolonged episode of intrahepatic cholestasis with severe coagulopathy after acute hepatitis A. Total bilirubin was elevated up to 835 µmol/L and INR was 3.6. The manifestations of vitamin K-associated coagulopathy were controlled after the first dose of parenteral menadione sodium bisulfite. Glucocorticosteroids, ursodeoxycholic acid and plasmapheresis turned ineffective in the treatment of hyperbilirubinemia. Due to long-persisting cholestasis resistant to conservative therapy, the patient was considered for inclusion to the liver transplant waiting list. However, spontaneous resolution of the cholestatic episode was achieved at 5 months after the onset of manifestations. Benign recurrent intrahepatic cholestasis type 2 was diagnosed on the basis of the specific clinical signs, laboratory blood tests and genetic testing.

Conclusion. The present Case Report shows a long-lasting episode of cholestasis with severe coagulopathy in acute hepatitis A in a patient with benign recurrent intrahepatic cholestasis with subsequent spontaneous resolution of the clinical symptoms at 5 months after their manifestation onset. Therefore, the differential diagnosis of benign recurrent intrahepatic cholestasis should be considered prior to liver transplantation in patients with intrahepatic cholestasis.

483-490 234
Abstract

Objective. The paper aims at demonstrating the efficacy of endovascular interventional techniques in the treatment of rare vascular complications after kidney transplantation.

Material and methods. Recipients of renal grafts obtained from a deceased donor developed the following complications: a false aneurysm of the interlobar renal artery after lymphocele puncture in one case and a subintimal hematoma of the external iliac artery with subocclusion of the latter and impaired perfusion of the renal graft in the other one.

Results. These complications were successfully managed using X-ray endovascular technologies, which allowed saving the renal grafts in both cases with satisfactory long-term results.

Conclusion. Early diagnosis and endovascular technologies made it possible to cope with complications minimally invasively and prevent the development of adverse events in the long term.

491-499 415
Abstract

Background. Transplantation is the only effective method of helping patients with irreversible damage of the lung function when the possibilities of other treatment methods have been exhausted. At the same time, a chronic graft rejection is the main cause of the loss of the donor organ function in the long-term period, developing in more than 50% of patients within 5 years after surgery. Given irreversible lung damage with loss of lung functions, the only effective treatment method for this patient population is retransplantation, which is associated with high risks of complications and a long rehabilitation of the patient in the postoperative period.

Objective. Demonstration of the first Russian experience of bilateral lung retransplantation in a patient after a longterm extracorporeal oxygenation.

Results. The article presents the description of the first experience of bilateral lung retransplantation in Russia performed in a patient with a chronic rejection 4.5 years after the primary transplantation performed for end-stage lung lesions in non-langerhans cell histiocytosis. In the 96-day period of waiting for a donor organ, the patient's gas-exchange lung function was compensated by using veno-venous extracorporeal membrane oxygenation.

Conclusions. Retransplantation is an effective method of treatment for patients with irreversibly damaged lung function, but still remains an operation associated with high risks of complications and unfavorable outcome.

500-506 327
Abstract

Objective. The aim of our work was to evaluate the immediate and remote results of ligation of splenic artery aneurysm in orthotopic liver transplantation in patients with decompensated liver cirrhosis.

Material and methods. From June 2018 to May 2024, 232 liver transplants from a posthumous donor were performed at the Surgical Clinic of the Moscow Multidisciplinary Scientific and Clinical Center n.a. S.P. Botkin. In 4 patients (1.7%), the presence of aneurysmal dilatation of the splenic artery was revealed at the preoperative stage. During orthotopic liver transplantation, patients underwent ligation of the splenic artery proximal and distal to the aneurysms.

Results. Mean time for the isolation and ligation of the splenic artery aneurysm was 18.4±3.3 minutes. In no case was there any damage or bleeding from either the branches or the aneurysm of the splenic artery; and there was no damage to the spleen. No adverse events related to the splenic artery aneurysm ligation were recorded in either early or late postoperative periods. In all cases, the control examination did not reveal any ischemic changes in the splenic parenchyma.

Conclusion. Ligation of the splenic artery aneurysm during orthotopic liver transplantation is a safe, effective and necessary surgical intervention that can improve long-term results by reducing the risk of death from aneurysm rupture in the postoperative period.

EXPERIENCE IN PRACTICAL TRANSPLANTOLOGY

507-518 249
Abstract

Background. To date, various non-invasive techniques or tests have been proposed that can identify a high risk of bleeding from esophageal varices. Despite a significant number of studies revealing the presence of venous varices as a likely factor for the development of bleeding due to their rupture, data on predictors of the first episode of bleeding are few and often contradictory.

Objective. To determine non-invasive independent predictors of the first episode of bleeding in patients waiting for liver transplantation.

Material and methods. A comparative retrospective study was conducted in 729 patients with decompensated cirrhosis who were on the waiting list for liver transplantation. We analyzed demographic, clinical and laboratory parameters, MELD-Na, Child-Turcotte-Pugh scores, FIB-4 Index, APRI, AST/ALT ratio; we determined the liver stiffness, spleen diameter, studied the liver stiffness-spleen diameter to platelet ratio risk score (LSPS model), platelet count/spleen diameter ratio in the groups of patients with the first episode of bleeding (n=334) and without it (n=395). The accumulated risks in the compared groups were assessed using a model of proportional hazards (Cox regression) in univariate and multivariate analysis.

Results. During 48 months of follow-up from the time of patient placement on the liver transplant waiting list, primary bleeding events developed in 45.8%. The risk of developing the first episode of bleeding progressively increased with LSPS >3.5 and reached maximum values in patients awaiting liver transplantation within 48 months of inclusion in the waiting list, while with LSPS <3.5 the risk was minimal.

Conclusion. Independent non-invasive predictors of the first episode of bleeding are a high level of AST, a high fibrosis index (FIB-4), a decrease in the ratio of platelet count/spleen diameter and a high LSPS value. Their application in clinical practice will improve the results of dispensary and screening examinations of patients with portal hypertension.



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ISSN 2074-0506 (Print)
ISSN 2542-0909 (Online)