Living-related Liver Transplantation Research Articles

Understanding the living-related pediatric liver transplantation donor's decision process: A questionnaire-based retrospective study.

To analyse the donor characteristics and understand the sociocultural and familial aspects of the decision to donate for living donor liver transplant. This is a retrospective study done in the Department of Pediatric Gastroenterology and Hepatology of a liver transplant centre. We enrolled the consenting donors of pediatric liver transplantation between January 2020 and January 2022. The study was conducted through an anonymized questionnaire which was drafted in a multiple-choice format. The questionnaire had three domains having questions pertaining to demographic details, donor characteristicsand sociofamilial aspects of the decision-making process. The study cohort consisted of 50 donors, 23 males (46%) and 27 females (54%), with the mean age being 31.8 ± 5.6 years. Parent-to-child was the most frequent relationship (n = 39, 78%). More than half of our donors had annual income <2.5lakh/annum or <3500 USD(n = 27, 54%). Twenty-six (52%) responders had >4 members in their family; 62% were residing in urban areas and 52% of the donors were graduates. The main source of information regarding the feasibility of living donor liver transplantation wasprimary physicians in 46%. Financial management was the main hurdle in 72%. Majority (74%) denied any effect on their marital relationship and 6% of donors thought that the degree of information provided to them before the transplantation regarding donation was insufficient. Our study serves as an essential tool for health professionals to provide sufficient support to the donor. Clinical outcomes and cost must be part of the discussion between caregivers, health professionalsand fund contributors.

Acute kidney injury after living‐related liver transplantation in infants with biliary atresia: A retrospective study

AbstractAlthough acute kidney injury (AKI) is a frequent postoperative complication after liver transplantation, renal function following living‐related liver transplantation (LRLT) in infants remains understudied. The aim of this study was to identify the prevalence of AKI and the impact of AKI on outcomes in infant recipients with biliary atresia. We retrospectively reviewed infants who underwent LRLT surgery between January 2018 and January 2021. The primary outcome was the risk of postoperative AKI occurrence in the first 7 postoperative days. A multivariate regression analysis model was used to investigate risk factors for AKI, and the incidence and impacts of AKI on outcomes were analyzed. A total of 98 patients were included in the analysis. AKI occurred in 59 patients (60.2%) within 7 days after surgery. Logistic regression analysis revealed that preoperative transfusion (p &lt; 0.05) and lower serum creatinine (SCr) (p &lt; 0.05) were independent risk factors for AKI. The incidence of serious complications was significantly higher in the AKI group than in the non‐AKI group (p &lt; 0.05). The postoperative mechanical ventilation time (p &lt; 0.05) and hospital stay (p = 0.019) were significantly longer in the AKI group. There was no evidence of chronic kidney disease (CKD) in any surviving infants within 1 year after surgery. In conclusion, AKI is common in infant LRLT (60.2%), and preoperative transfusion and lower SCr levels were independently associated with AKI. AKI may be associated with the incidence of serious complications, prolonged use of ventilators, and hospital stays. No CKD occurred within 1 year.

Tacrolimus-associated sinusoidal obstruction syndrome after living-related liver transplantation

Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease, is manifested by obliterating inflammation of the terminal hepatic veins, characterized by hepatomegaly, right upper quadrant pain, jaundice and ascites, and most often occurs in patients after hematopoietic stem cell transplantation and usually in those who received platinum-based drugs. Cases of SOS development in patients after transplantation of solid organs (lungs, pancreas, liver) are also reported in the world literature. These incidents are rare, and isolated and poorly studied after living-related liver lobe transplantation. The diagnosis is based on clinical signs, imaging techniques (according to ultrasound and radiological methods of examination), histological assessment of liver biopsy. Tacrolimus has been reported to be a causative agent that potentially plays a role in the pathophysiological mechanism of SOS. Aim. To study the relationship between the use of prolonged-release tacrolimus and the development of SOS in patients after living-related liver transplantation. Clinical case. In this article, we present a case of SOS after living-related liver transplantation which was associated with a toxic effect of prolonged-release tacrolimus (“Envarsus”). In a 55-year-old man, after living-related liver transplantation, high blood concentrations of tacrolimus associated with uncontrolled drug intake were detected. When performing a number of laboratory and instrumental methods of examination due to a massive ascites manifestation, the diagnosis of SOS was made. The study was carried out in accordance with the principles of the Helsinki Declaration. The informed consent was obtained from the patient for conducting the studies. Conclusions. By ruling out other possible contributing factors, including an acute rejection crisis, it was concluded that prolonged-release tacrolimus (“Envarsus”) was the cause of SOS.

Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report

BackgroundBiliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy.Case presentationAn 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution.ConclusionsDelayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

Living-related partial liver transplantation in unresectable liver metastatic colorectal cancer. A case report

Aim. The purpose of the article is to study the outcome of using living-related partial liver transplantation in the treatment of unresectable liver metastatic colorectal cancer. Case report. A woman, born in 1989, applied to the Medical Center Universal Clinic “Oberig” with a diagnosis of stage IV sigmoid colon cancer pT4N2M1 with synchronous liver metastases after sigmoidectomy and adjuvant chemotherapy. The patient underwent surgical intervention to the extent of right-sided hemihepatectomy with total caudate lobectomy, enucleation of metastases from the left liver lobe, cholecystectomy, extended lymphadenectomy, followed by systemic antitumor therapy. Six months later, according to laboratory and instrumental examinations, the progression of the disease was revealed in the form of new metastases development in the left liver lobe. After a thorough examination, a decision was made to treat the patient by living-related partial liver transplantation. On February 16, 2021, the patient underwent orthotopic transplantation of the left liver lobe from a living-related donor. The patient was discharged on the 31st postoperative day in a satisfactory condition. According to a control MRI after discharge, no signs of disease progression were detected. In the post-transplantation period, the patient developed an acute steroid-resistant rejection requiring antiplatelet immunoglobulin prescription. Three months after discharge, the patient was diagnosed with a high stricture of the bilio-biliary anastomosis, so resections of liver segment IV, hepaticocholedochus, and bihepaticojejunostomy on a defunctionalized Roux loop of the small intestine were performed. In the post-transplantation period, no signs of disease progression were detected, and no special antitumor treatment was used. Conclusions. Liver transplantation is an effective and radical method of treatment for patients with unresectable liver metastatic colorectal cancer.

Effect of intraoperative dexmedetomidine on hepatic ischemia-reperfusion injury in pediatric living-related liver transplantation: A propensity score matching analysis

BackgroundHepatic ischemia-reperfusion injury (HIRI) is largely unavoidable during liver transplantation (LT). Dexmedetomidine (DEX), an α2-adrenergic agonist, exerts a variety of organ-protective effects in pediatric populations. However, evidence remains relatively limited about its hepatoprotective effects in pediatric living-related LT.MethodsA total of 121 pediatric patients undergoing living-related LT from June 2015 to December 2018 in our hospital were enrolled. They were classified into DEX or non-DEX groups according to whether an infusion of DEX was initiated from incision to the end of surgery. Primary outcomes were postoperative liver graft function and the severity of HIRI. Multivariate logistic regression and propensity score matching (PSM) analyses were performed to identify any association.ResultsA 1:1 matching yielded 35 well-balanced pairs. Before matching, no significant difference was found in baseline characteristics between groups except for warm ischemia time, which was longer in the non-DEX group (44 [38–50] vs. 40 [37–44] min, p = 0.017). After matching, the postoperative peak lactic dehydrogenase levels decreased significantly in the DEX group than in the non-DEX group (622 [516–909] vs. 970 [648–1,490] IU/L, p = 0.002). Although there was no statistical significance, a tendency toward a decrease in moderate-to-extreme HIRI rate was noted in the DEX group compared to the non-DEX group (68.6% vs. 82.9%, p = 0.163). Patients in the DEX group also received a significantly larger dosage of epinephrine as postreperfusion syndrome (PRS) treatment (0.28 [0.17–0.32] vs. 0.17 [0.06–0.30] µg/kg, p = 0.010). However, there were no significant differences between groups in PRS and acute kidney injury incidences, mechanical ventilation duration, intensive care unit, and hospital lengths of stay. Multivariate analysis revealed a larger graft-to-recipient weight ratio (odds ratio [OR] 2.657, 95% confidence interval [CI], 1.132–6.239, p = 0.025) and intraoperative DEX administration (OR 0.333, 95% CI, 0.130–0.851, p = 0.022) to be independent predictors of moderate-to-extreme HIRI.ConclusionThis study demonstrated that intraoperative DEX could potentially decrease the risk of HIRI but was associated with a significant increase in epinephrine requirement for PRS in pediatric living-related LT. Further studies, including randomized controlled studies, are warranted to provide more robust evidence.

Historical Background of Pediatric Kidney and Liver Transplantation in Turkey

The cornerstone events of kidney and liver transplant history in Turkey are summarized herein. In 1975, we performed the first pediatric living-related renal transplant in Turkey. We followed this in 1978 with the first deceased donor kidney transplant, using an organ supplied by Eurotransplant. In 1979 the law on harvesting, storage, grafting, and transplant of organs and tissues was enacted; the first local deceased donor kidney transplant was performed by our team in 1979. In 1988, another ground-breaking event in Turkey, the Middle East, and North Africa was successfully achieved: the first successful deceased-donor liver transplant, and in 1990, the first pediatric living-related segmental liver transplant in Turkey, the region and Europe was performed by our team. One month later, an adult-to-adult living-related liver transplant (left lobe) in the World was successfully performed. On May 16, 1992, we performed the first combined liver-kidney transplant from a living-related donor, which was the first operation of its kind in the World. Between November 1975 and January 2022, we have performed 3288 kidney (380 pediatric) at the Hacettepe University Hospitals and later on at Baskent University; since 1988, 701 (334 pediatric) liver transplants have been performed. In over 40 years of kidney and liver transplants history in Turkey, 46876 kidney (2502 pediatric patients) and 18203 liver (2612 pediatric patients) transplants have been performed nationwide. In 2001, the Ministry of Health established the National Coordination Center as an umbrella organization to promote transplant activities, especially for deceased donor organ procurement. Transplant activities are accelerating daily throughout the country, but deceased donors are still far below the desired rates.

Safety and efficacy of pediatric liver transplantation in Saudi Arabia

Evidence shows that liver transplantation is a good management choice for pediatric patients with severe hepatic disorders. In addition, the approach can be used for managing different hepatic disorders, including metabolic and familial ones. Therefore, liver transplantation is indicated and should be urgently conducted to intervene against further deterioration in the health status of the affected patients and enhance their prognosis. Various investigations in the literature validated the efficacy of the modality for different age groups, although many of them reported the incidence of different related complications. In Saudi Arabia, not many studies reported the safety and efficacy of liver transplantation for pediatric patients. The present literature review provided insight regarding the safety and efficacy of the procedure for this population group. We can conclude that liver transplantation in pediatric settings is a safe and productive approach that can be successfully conducted with a favorable prognosis. Moreover, it has been shown that living-related liver transplantation is more favorable than cadaveric-related liver transplantation in these settings, especially when there is a graft shortage, as reported in Saudi Arabia. Despite the favorable outcomes, further reports are still needed for validating the current evidence.

The future of pediatric liver transplantation in the Children’s Medical Center—Living related Liver Transplant between the adjacent independent hospitals—

The future of pediatric liver transplantation in the Children’s Medical Center—Living related Liver Transplant between the adjacent independent hospitals—

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Complete Remission of Refractory Immunothrombocytopenic Purpura After Tacrolimus Replacement With Cyclosporine in a Case of Living Related Liver Transplant

Immunothrombocytopenic purpura is a possible complication after liver transplant. The therapy for immunothrombocytopenic purpura after liver transplant is similar to that of primary immunothrombocytopenic purpura. This therapy consists of corticosteroids, intravenous immunoglobulin, and immunosuppressive agents such as cyclosporine and rituximab. There are a few cases of immunothrombocytopenic purpura in patients who recovered after cessation of tacrolimus administration. Here, we show an intractable case of immunothrombocytopenic purpura in a living related liver transplant recipient treated with some of these. We observed complete remission after switch ofthe immunosuppressive agent from tacrolimus to cyclosporine. The patient was an infant girl aged 18 months who underwent livingr elated liver transplant for biliary atresia when she was 6 months old. Liver graft was a left lateral segment from her father. Purpura and severe thrombocytopenia developed after 11 months.There was no effect of the first-line therapies, as described in the Japan guidelines for immunothrombocytopenic purpura.Thrombocytopenia was extreme, as shown by a blood count of 0 platelets/μL. Administration of rituximab was started. However, her platelet count had not increased 8 weeks after rituximab initiation. As a trial therapy, we switched tacrolimus to cyclosporine. She showed complete remission 1 month after this drug conversion. Thus, a switch from tacrolimus to other immunosuppressive agents as a therapy for immunothrombocytopenic purpura after living related liver transplant should be considered.

Long Term Outcomes of Liver Transplantation For Patients With Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). Data on the long-term outcomes of living-related LT for AIH are limited and inconsistent. The present study aimed to assess the long-term outcomes of deceased donor LT (DDLT) and living donor LT (LDLT) for AIH. All patients who received transplants for AIH-related cirrhosis from 2001 to 2018 were included in this study. Seventy-four patients (31 male, 43 female) received LT. The average follow-up was 7.9 ± 6.9 years (median = 7.2 years), average age was 34.3 ± 13.8 years, and average Model for End-Stage Liver Disease (MELD) score was 23.6 ± 8.5. Thirty-six (49.3%) patients received a graft from a living donor, and 83% of patients were maintained on steroids. The 1-, 3-, 5-, and 10-year survival rates of patients were 91%, 89%, 87%, and 82% and of grafts were 89%, 88%, 86%, and 76%, respectively. In univariate analysis, MELD score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.17; P = .028), donor age (OR per 5 years, 1.45; 95% CI, 1.07-2.02; P = .021), donor type (OR LDLT vs DDLT, 0.19; 95% CI, 0.04-0.67; P = .017), and renal function (OR glomerular filtration rate <60 vs ≥60 mL/min/m2, 7.41; 95% CI, 1.88-31.25; P = .004) were significant predictors of graft survival; however, none of the factors remained significant in multivariate analysis. We have shown the highest reported long-term survival rates in LT for AIH, including a large number of patients who underwent LDLT. Standardized management and immunosuppressive therapy, including the maintenance of a low-dose steroid protocol, may have contributed to this outcome.

The Contribution of Serum Complement Component 3 Levels to 90-Day Mortality in Living Donor Liver Transplantation.

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] mg/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.

Cardiac Intervention Before Liver Transplantation

Cardiovascular complication is one of the leading causes of mortality after liver transplantation (LT). Thus, a thorough cardiac evaluation is a must before proceeding to a liver transplant surgery. Percutaneous coronary intervention (PCI) with stent and to a lesser extent coronary artery bypass grafting (CABG) are both valuable treatment options for patients with coronary artery disease. A retrospective, single-center study that included patients who underwent cardiac intervention and subsequent LT for end-stage liver disease. All patients who had PCI or CABG were included in the study. Twenty-nine adult patients out of 51 had a cardiac intervention before liver transplantation. Twenty-four patients had a diagnostic PCI, 3 patients had therapeutic PCI with stent, and 2 had failed PCI and proceeded to CABG before liver transplant. The mean age of the patients was 60.5 years. There were 24 men. All patients had cirrhosis. The 2 CABG cases were done during the same admission with a 13- and 18-day interval between the CABG and the transplantation. Both cases were live-related liver transplantation. No mortality was reported. In case of PCI failure, CABG may be a valuable and safe treatment option for cirrhotic patients as a preparation for liver transplantation. Live donor liver transplantation may be a good back-up for those patients in case they develop hepatic decompensation.

A Combined Program of Cadaveric and Living-Related Liver Transplantation in a Single Center: An Experience of 1,000 Operations

A Combined Program of Cadaveric and Living-Related Liver Transplantation in a Single Center: An Experience of 1,000 Operations

Living-related donor liver transplantation for pediatric patients with Caroli disease: A case report

Living-related donor liver transplantation for pediatric patients with Caroli disease: A case report

Recent advances in the surgical management of hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) is increasing, despite effective antiviral treatment for hepatitis B (HBV) and C virus infection and the application of preventive measures such as vaccination at birth against HBV infection. This is mainly due to the increase in metabolic syndrome and its hepatic components, nonalcoholic fatty liver disease and steatohepatitis. Liver resection and transplantation are the main treatment options, offering long-term survival and potential cure. In this review, the recent advances in the surgical management of HCC are presented. More specifically, the role of liver resection in the intermediate and advanced stages, according to the Barcelona Clinic Liver Cancer classification, is analyzed. In addition, the roles of minimally invasive surgery and of living-related liver transplantation in the management of patients with HCC are discussed. Finally, recent data on the role of molecular markers in the early diagnosis and recurrence of HCC are presented. The management of HCC is complex, as there are several options for each stage of the disease. In order for, each patient to get the maximum benefit, an individualized approach is suggested, in specialized liver units, where cases are discussed in multidisciplinary tumor boards.

Von Willebrand factor to protein C ratio-related thrombogenicity with systemic inflammation is predictive of graft dysfunction after liver transplantation: Retrospective cohort study

IntroductionEarly allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation. Material and methodsOf 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed. ResultsThe prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28–5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1–4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%. ConclusionsPretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation.

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.

Understanding the Long-Term Impact of Living-Related Liver Transplantation on Youth and Young Adults and their Family

PurposeThe purpose of this mixed methods study was to better understand the long term impact of living-related liver donation (LRLD) on youth and young adult (YYA) recipients and their family. Design and methodsSemistructured interviews were conducted with YYA, aged 11–18 years, who received a living donation from a parent. Interviews were audiotaped, transcribed, and analyzed to aggregate themes that represented the participants' views as live-liver recipients. An ethnographic process was conducted to understand the participants' social behavior. At interview, participants completed a demographics questionnaire and the Youth Quality of Life Instrument-Research Version (YQOL-R). ResultsThirteen adolescents were interviewed; six were re-interviewed as key informants. Three major categories were created from the data: Developing Identity, Redefining Family Relationships, Feeling Gratitude to Donors. The overarching theme was Resiliency. Findings from the YQOL-R showed no difference in overall scores or separate domains when compared with a reference population with no chronic illness. ConclusionQualitative and quantitative data highlight the positive effect that LRLD can have on pediatric patients as they transition from childhood to adolescence to young adulthood. Practice implications: As pediatric transplant centers in the United States soon mark 30 years of performing live-liver donation, recipients are becoming adults and understanding more clearly that the long-term effects of such donations will lead to improvements in future care.