Living-related Transplantation Research Articles

Organ donation for transplantation in Bangladesh.

Organ transplantation is a treatment of modern medicine and technology that saves the lives of hundreds and thousands of medically suitable end-stage organ failure patients. The first successful kidney transplantation from living-related donors in Bangladesh was successfully performed in 1982 and regularly from 1988. This was then followed by deceased cornea in 1984, and liver and bone marrow from living-related donors in 2010 and 2014 respectively. The Human Organ Transplantation Act was first passed by the parliament of Bangladesh in1999, allowing both brain death donation and living-related donor transplantations. Before the legislation of 1999, religious approval (fatwa) from religious leaders was obtained that acknowledged brain death donation and allowed deceased donation for transplantations. The existing act was revised in January 2018. From 1982 to 2017, only 1791 kidney, six liver, and 25 bone marrow transplantations were carried out from living-related donors. Deceased transplantations have not been started yet in Bangladesh. Only 5500 deceased corneas have been used for transplantation purposes. There are long-standing concerns about the lack of transplantation of the vital organs from deceased donors in Bangladesh and its impact on the increasing demand for procuring organs from living donor. On the other hand, living-related donors are very scarce. Numerous vital organ failure patients are often forced to buy organs from poor people. It creates an illegal and unethical market in human organs in Bangladesh.

Review of surgical techniques for performing laparoscopic donor hepatectomy

Living related liver transplantation has proved to be an effective, safe and radical method for treating end-stage liver diseases. In the last decade, a laparoscopic approach to donor hepatectomy has been gradually introduced into clinical practice. According to world literature, there are presently no uniform standards for performing laparoscopic liver resections in living donors. This literature review considers almost all methods for performing this surgery in living donors. These methods are described in transplant centers around the world.

SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1

SCYL1 disease results from biallelic pathogenic variants in SCYL1. We report two new patients with severe hepatic phenotype requiring liver transplantation. Patient charts reviewed. DNA samples and skin fibroblasts were utilized. Literature was reviewed. 13-year-old boy and 9-year-old girl siblings had acute liver insufficiency and underwent living related donor liver transplantation in infancy with no genetic diagnosis. Both had tremor, global developmental delay, and cognitive dysfunction during their follow-up in the medical genetic clinic for diagnostic investigations after their liver transplantation. Exome sequencing identified a likely pathogenic variant (c.399delC; p.Asn133Lysfs*136) in SCYL1. Deletion/duplication analysis of SCYL1 identified deletions of exons 7-8 in Patient 1. Both variants were confirmed in Patient 2 and the diagnosis of SCYL1 disease was confirmed in both patients at the age of 13 and 9 years, respectively. SCYL1 protein was not expressed in both patients' fibroblast using western blot analysis. Sixteen patients with SCYL1 disease reported in the literature. Liver phenotype (n = 16), neurological phenotype (n = 13) and skeletal phenotype (n = 11) were present. Both siblings required liver transplantation in infancy and had variable phenotypes. Exome sequencing may miss the diagnosis and phenotyping of patients can help to diagnose patients.

Our Experience of Living Related Liver Transplantation for PFIC Types 1 and 4

Our Experience of Living Related Liver Transplantation for PFIC Types 1 and 4

Outcome of Portal Vein Reconstruction Using Branch Patch Anastomosis in Pediatric Living Related Liver Transplant Recipients Weighing Less than 10 kg

Pediatric living related liver transplantation (PLRLT) in children less than 10 Kg of weight with Portal vein (PV) reconstruction in atretic and hypoplastic portal vein is challenging. Portal venoplasty using branch patch anastomosis is one of the techniques that are being advocated for these groups of patients.

Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies

BackgroundApproximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT1R-Ab). While the role of AT1R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT1R-Ab.CaseWe report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT1R-Ab-mediated chronic ABMR. Because this antibody persisted during 4 years of hemodialysis, for the 2nd kidney transplantation (living-related transplantation from his mother), he underwent a desensitization regimen consisting of 15 plasmapheresis sessions, infusions of intravenous immunoglobulin G and thymoglobulin, as well as pharmacological blockade of the Angiotensin II (AT II) pathway by candesartan. This intense desensitization regimen transiently decreased elevated AT1R-Ab titers, resulting in stable short-term kidney allograft function. The subsequent clinical course, however, was complicated by acute cellular rejection and chronic ABMR due to persistent AT1R-Ab and de novo HLA-DSA, which shortened allograft survival to a period of only 4 years.ConclusionThis case highlights the difficulty of persistently decreasing elevated AT1R-Ab titers by a desensitization regimen for re-transplantation and the detrimental effect of the interplay between AT1R-Ab and HLA-DSA on kidney transplant survival.

Outcome of hepatitis C-related liver transplantation in direct-acting antiviral era.

Hepatitis C virus (HCV) has become an easily treatable disease after the introduction of sofosbuvir-based direct-acting antiviral (DAA) regimens. This is a large single center experience of changing severity and outcome profile of HCV-related liver disease after availability of DAAs. A retrospective analysis of prospectively collected liver transplantation (LT) database of adults (age > 18years at the time of LT) was performed from June 2010 to July 2018. A total of 410 patients (including 26 co-infection with hepatitis B) underwent LT for hepatitis C-related decompensated cirrhosis and/or hepatocellular carcinoma (HCC) out of 1754 adult transplantation in the defined period. The study group comprised of 296 males and 114 females aged 52.1 ± 7.9years. HCV-related decompensated cirrhosis and/or HCC as indication of LT was present in 289/1016 (28.4%) during 2010-2014, which was reduced to 121/738 (16.3%) during2015-2018 (p = 0.000). The LT recipients for HCV-related cirrhosis had significantly lower Child's and model for end-stage liver disease (MELD) score during 2015-2018 as compared to that during2010-2014; Child's score was 7.9 ± 2.2 vs. 8.6 ± 2.1, p = 0.003; MELD scorewas 13.9 ± 5.3 vs. 17.1 ± 5.8, p = 0.000, respectively. There was a trend towards better survival in HCV patients during 2015-2018 as compared to that during 2010-2014. Significantly more patients had HCV RNA negative status before LT during 2015-2018 (38.8% vs. 13%, p = 0.000); moreover, the proportion of LT for decompensated cirrhosis (without HCC) decreased significantly in the latter period, 64.0% vs. 42.1% (p = 0.000). In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. There is a trend towards better patient survival.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study.

SummaryIn this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living‐related donor (LRD) or living‐unrelated donor (LUD). Adult patients in the ERA‐EDTA Registry who received their first kidney transplant in 1998–2017 were included. Ten‐year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five‐year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7–4.6) and 10.8% (95% CI: 10.1–11.5) versus 6.5% (95% CI: 5.7–7.4) and 12.2% (95% CI: 11.2–13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87–1.13) for patient survival and 1.03 (95% CI: 0.94–1.14) for graft survival. Unadjusted risk of death‐censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04–1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death‐censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.

Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study

To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). In this multicenter integrated analysis, FOLE recipients (1g/kg/d) (n=189) were compared with historical controls administered SOLE (≤3g/kg/d) (n=73). Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8mg/dL vs 3.0mg/dL; P<.0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P<.0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P<.02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P≤.0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P=.0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2mg/dL; 8% vs 35% at DB of 12.87mg/dL; P=.0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2mg/dL; 17% vs 23% at a DB of 12.87mg/dL; P=.36 for both). FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2mg/dL. Clinicaltrials.gov: NCT00910104 and NCT00738101.

Living Related Liver Transplantation for Metabolic Liver Diseases in Children.

Metabolic liver diseases (MLDs) are a heterogeneous group of inherited conditions for which liver transplantation can provide definitive treatment. The limited availability of deceased donor organs means some who could benefit from transplant do not have this option. Living related liver transplant (LrLT) using relatives as donors has emerged as one solution to this problem. This technique is established worldwide, especially in Asian countries, with shorter waiting times and patient and graft survival rates equivalent to deceased donor liver transplantation. However, living donors are underutilized for MLDs in many western countries, possibly due to the fear of limited efficacy using heterozygous donors. We have reviewed the published literature and shown that the use of heterozygous donors for liver transplantation is safe for the majority of MLDs with excellent metabolic correction. The use of LrLT should be encouraged to complement deceased donor liver transplantation (DDLT) for treatment of MLDs.

GENDER INEQUALITY IN ACCESS TO RENAL REPLACEMENT THERAPY IN PEDIATRIC POPULATION: EXPERIENCE FROM A SINGLE CENTER

Introduction: Gender inequality in access to dialysis facility and renal transplantation is extensively reviewed amongst adult patients. However, less is known about extent of gender inequality among pediatric CKD population. Materials and Methods: This was a retrospective data analysis of pediatric kidney transplants performed at single center from Gujarat from 2005 to 2019. Data was analyzed to look for gender inequality among donors and recipients. Further, children with ESRD on dialysis at center were observed for gender differences. We also reviewed gender difference among these ESRD patients for their process of transplantation. Results: During 2005 to 2019, 412 pediatric transplants were performed. Out of these, 329 (79.85%) were live renal transplants and 83 (20.14%) were deceased donor organ transplants. Remarkable gender difference was seen with boys (323, 78.4%) being majority of recipients versus girls (89, 21.6%). Also, among live donors, females have been major donors (237, 72%). However, among 83 cadaver donors, 53 (63.8%) were male. Currently, total 326 patients are on dialysis. Out of 326 ESRD patients on dialysis,207 (63%) are boys as compared to 119(37%) girls. Among these 326 patients 10 are under live related transplant work up (7 male, 3 female). Out of 326 patients, 34 are registered under state cadaver organ donor program, amongst them 22 (64%) are boys. Conclusion: Gender inequality in access to renal replacement therapy does exist. Girls have lower chances of receiving dialysis and transplantation than boys, but female constitute majority of living kidney donors. However, reasons for this gender difference for treatment choices is not very well studied, but sociocultural influences and socioeconomic factors are possible causes. Greater attention is necessary to improve the outcome of pediatric female patients with ESRD.

Alopecia in Children Following Living Related Liver Transplantation

IntroductionAlopecia is a common complication in patients following kidney transplantation; however, reports regarding liver transplantation patients are still few. MethodsThis study followed 111 children who underwent living related liver transplantation. Alopecia patients and its possible risk factors were analyzed. ResultsAlopecia occurred in 3 patients (2.7%). Underlying diseases were biliary atresia and Alagille syndrome. Clinically significant alopecia (universal alopecia) occurred in 1 patient with Alagille syndrome. All patients received tacrolimus as their immunosuppression drug. None of the patients who received cyclosporine experienced alopecia. The onset of alopecia ranged from 7 to 28 months after transplantation. Alopecia was treated with a topical corticosteroid and topical tacrolimus, but 1 patient with clinically severe alopecia required conversion from tacrolimus to cyclosporine A. ConclusionsAlopecia is 1 complication seen in children receiving tacrolimus therapy following living donor liver transplant. Prompt management of this cosmetic complication should be done to ensure patients’ compliance to medication regimen.

COVID-19 and kidney transplantation: an Italian Survey and Consensus.

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions.Electronic supplementary materialThe online version of this article (10.1007/s40620-020-00755-8) contains supplementary material, which is available to authorized users.

О родственной трансплантации

Article describes the judgment on the nature of living-related transplantation. We must proceed from the fact that any patient who is doomed to death, while breathing, remains a person aimed at the future. With a related organ transplant, doctors act morally, but with elements of error. And if you take into account the fact those doctors have an alternative way — transplantation of organs taken from a corpse; that is, in a linear order, then they would act morally without any reservations. In moral matters, doctors should strive for an affordable optimum, guided by moral responsibility.

Experience in living related liver transplantation of one hospital team

Experience in living related liver transplantation of one hospital team

PNPLA3 L148M (rs738409) polymorphism as a risk for new onset diabetes mellitus and obesity in non-NASH/cryptogenic living related donor liver transplant recipients

BackgroundLiver transplantation is considered the main treatment for end stage liver disease and the early stages of hepatocellular carcinoma. Long-term metabolic outcomes after liver transplantation affect morbidity and mortality, and the genetic rule has not been well studied for such complications. The patatin-like phospholipase domain-containing 3 (PNPLA3) gene L148M (rs738409) polymorphism has been associated with a wide spectrum of metabolic affection, but mainly fatty liver, in the general population. Here, we demonstrate the impact of the PNPLA3 polymorphism on living related donor liver transplantation (LRDLT) recipients' new onset diabetes mellitus and obesity. MethodsGenotyping of PNPLA3 rs738409 variants was analyzed using an allele discrimination assay with real-time PCR in 158 LRDLT donors and their recipients, who had no history of diabetes mellitus or fatty liver disease before transplantation and survived >1 year after transplantation. The LRDLT recipients were assessed for the development of new onset diabetes and the risk of obesity 1 year after transplantation. ResultsRecipients' PNPLA3 genotypes were associated with the development of new onset diabetes mellitus after liver transplantation (CC genotype 18.8%, CG genotype 39.1%, GG genotype 42.2%, P = 0.000; GG genotype: odds ratio 24, (95% CI 8.1–70.5). Logistic regression for the predictors of new onset diabetes showed significant risk for recipients with the PNPLA3 CG genotype (P = 0.000, OR 5.5, 95% CI 2.4–12.7) and the GG genotype (P = 0.000, OR 32, 95% CI 9–116.7). In recipients, the GG genotype enhanced the incidence of obesity, with an odds ratio of 3.8 (95% CI 1.6–8.9). The PNPLA3 gene of variants of donors did not show any significant variations with different parameters. ConclusionThe PNPLA3 L148M (rs738409) polymorphism of recipients, not donors carries a risk for new onset diabetes and obesity in LRDLT recipients post-transplant. That means there is a peripheral effect, rather than a central effect, of genotype.

Retrospective genetic analysis illustrates the spectrum of autosomal Alport syndrome in a case of living-related donor kidney transplantation

BackgroundKidney transplantation is the treatment of choice in end-stage renal disease due to Alport syndrome (AS). However, the chances of finding an adequate living-related donor in AS are much worse compared to non-heritable conditions. Successful cases of related living-donor transplantation mostly refer to X-linked AS but are rarely reported in genetically confirmed autosomal AS.Case presentationWe describe the outcome of an exceptional AB0-incompatible kidney donation from father to son in a family with altered COL4A3. While decision-making was based on extensive clinical donor evaluation prior to transplantation, we analyzed the underlying genetic background in retrospect and associated these findings with the phenotype in all available family members. While biallelic COL4A3 variants caused autosomal recessive AS (ARAS) in the son (recipient), heterozygous family members, including the father (donor), showed minimal renal involvement and high-frequency sensorineural hearing impairment later in life indicating mild autosomal dominant Alport syndrome (ADAS). The recipient’s successful participation in the European and World Transplant Games is a testament to the positive outcome of transplantation.ConclusionsIn summary, living-related donor transplantation may be successful in autosomal AS, provided that thorough clinical and genetic evaluation of potential donors is performed. However, unrelated kidney transplantation should be given priority upon unpredictable genetic risk. Individual genetic variant interpretation is an important component of personalized donor assessment and will help to better predict genetic risk in the future.

Liver Graft and Spleen Elastography After Living Liver Transplantation: Our First Results

Aim of the studyLiver transplantation is widely applied as a standard and effective management of end-stage liver diseases, hepatocellular carcinoma, and acute liver failure. Investigation of morphologic and functional changes in the transplanted graft, gastrointestinal system, and spleen after transplantation is an important ground for assessment of post-transplantation results, early changes related to complications, and evaluation of response to treatment modalities. The aim of this study was to investigate the dynamics of changes in elastography of the liver graft and spleen after living-related liver transplantation. Material and methodsThe study included 14 cirrhotic patients after living-related liver graft transplantation. Stiffness of the spleen and liver was evaluated before transplantation and at 1, 3, and 6 months after transplantation with a Supersonic Aixplorer Multi Wave device. Each procedure consisted of measuring the density in 10 points (spots) of the organ. The final result was calculated as the mean value of successful measurements (must have been > 60% of all measurements) and expressed in kilopascals. ResultsThe mean value of the liver and spleen stiffness before transplantation was 27 kPa (14–31 kPa) and 51 kPa (38–92 kPa), respectively. The stiffness of the spleen gradually reduced after transplantation to 40.3, 35.4, and 24.1 kPa (P = .001) at 1, 3, and 6 months. The stiffness of the liver graft in patients without complications was stable at 4–5 kPa, whereas the same value in patients with complications was increased (≥ 7.5 kPa). In 5 patients, endoscopic investigation confirmed the significant reduction of varicose veins after surgery. ConclusionElastography of the liver graft and spleen after liver transplantation can be recommended as a useful-for-patient 1-off method of investigation.

Ethical issues in living-related corneal tissue transplantation

The cornea was the first human solid tissue to be transplanted successfully, and is now a common procedure in ophthalmic surgery. The grafts come from deceased donors. Corneal therapies are...

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.