Living-related Transplantation Research Articles

#2311 Comparative analysis of knowledge and attitude regarding deceased donation in health care workers and the general population

Abstract Background and Aims Kidney transplantation is widely regarded as the best treatment option for end stage kidney disease. Despite being introduced over 40 years ago, the rate of kidney transplantation in Bangladesh is still very low at an average yearly rate of below 200 transplants over the last 5 years. Lack of donors and financial constraints have emerged as the biggest obstacles. Until recently, live related transplantation was the only option. There have been only 2 deceased transplantations last year, both from the same donor. In order to understand these low rates, we aim to understand the prevailing knowledge and attitude towards transplantation in the community and among the health care workers (HCWs) and how much they differ. Method This cross-sectional study has been ongoing since May 2022. It is a self-administered survey using a paper-based questionnaire, developed by the Asian Society of Transplant, asking about the respondent's knowledge and attitude regarding deceased organ donation in Bangladesh. The survey was administered in both HCWs and non-HCWs using a pre-tested questionnaire. The HCWs were recruited from 9 hospitals across Bangladesh and the non-HCWs were recruited from Universities, attendants accompanying patients in hospital waiting areas and a few offices. Convenient sampling technique was used. Data was analyzed by statistical analysis software (SAS) studio. Results Data was collected from 1351 respondents, 874 (65.6%) were HCWs and 458 (34.4%) were non-HCWs. Among the HCWs, 131 (15%) were doctors, 745 (85.2%) were nurses and 130 (14.9%) were final year medical students. Among the non-HCWs, business (10.3%), acting (8.9%) and teaching (4.4%) were the predominant professions. The mean age of the respondents was 36.4 (±14.1) years, 65.5% were female. The HCWs were significantly younger and had more females, mostly owing to the large sample of nurses. Twenty percent of the non-HCWs never heard about deceased donation compared to 3.4% HCWs (p < 0.0001). 79.5% of the HCWs said they knew very little or not at all about deceased donation. The self-assessment was about similar in the non-HCWs. Only 11.6% HCWs said they received education about organ donation, compared to 20.5% of the non-HCWs (p = 0.0004). Regarding deceased donation, 36% HCWs had a positive attitude, 58.7% were neutral and 5.3% were negative. Among the non-HCWs, 30.5% were positive, 35.5% were neutral and 34% were negative (p < 0.0001). Regarding willingness, 11.1% HCWs were very willing to donate themselves, 61.3% were contemplating and 27.6% were unwilling. Among the non-HCWs, 11.2% were willing to donate, 48.8% were contemplating and 40% were unwilling. When asked to list all reasons for not willing to donate, lack of information was most common (64.8% HCWs, 49.6% non-HCWs), followed by fear of donation (12.5% HCWs, 25.9% non-HCWs) and religious beliefs (6.8% HCWs, 15.6% non-HCWs) (p < 0.0001). When asked about the most reliable sources of information in order to promote deceased donation, the opinion varied widely. The most popular ones were online contents (63.9% HCWs, 12.4% non-HCWs), outdoor events (36.2% HCWs, 21.2% non-HCWs) and TV advertises (30% HCWs, 6.1% non-HCWs) (p < 0.0001). Conclusion The overall knowledge regarding deceased donation was poor. Most people had a neutral attitude towards donation and were contemplating donation themselves. The HCWs were more willing to donate. Lack of information was the leading reason behind unwillingness. Online promotions were considered the best modality for future promotion.

A longitudinal study of long-term renal outcome after pediatric liver transplantation in relation to CNI exposure.

Chronic kidney disease (CKD) is reported in 20%-30% of children after liver transplantation (LT). One of the proposed underlying causes is the long-term exposure to tacrolimus, a calcineurin inhibitor (CNI), which is the main immunosuppressive drug used after LT. Variation in tacrolimus absolute exposure and relative dose requirements are believed to be important risk factors for developing CNI-associated nephrotoxicity. To describe the long-term renal outcome of pediatric LT recipients and determine the effects of tacrolimus exposure on renal outcome parameters. Retrospective single center study of renal function (GFR, proteinuria) and pharmacokinetic parameters (C0 , AUC0-12h ) obtained during annual follow-up in children after liver transplantation, between 1998 and 2019. Relevant pharmacogenetic variants for tacrolimus disposition (CYP3A5 and ABCB1) were determined in recipients and donors. The evolution of individual renal function and tacrolimus exposure was evaluated using linear mixed models for repeated measurements. Twenty-six children were included (mean follow-up: 10.4 years (range 2-18.9)). Mean estimated GFR was 109.3 (SE: 7.4), vs. measured: 91.3 mL/min/1.73 m2 (SE: 6.3), which remained stable during follow-up. CKD stage ≥2 was observed in 32.8% of the visits based on eGFR versus 50.0% on mGFR. CKD stage ≥3 was uncommon (4.1% and 6.2% resp.). Mean tacrolimus C0 was 5.3 ng/mL (SE: 2.5) with a AUC0-12h of 72.7 ng*h/mL (SE: 30.3), which demonstrated a small decrease during follow-up. There was a negative correlation between C0 and mGFR (rS = -0.3; p < .001). We found no correlation between GFR and tacrolimus dose requirements ((ng/mL)/(mg/kg)) or pharmacogenetic background. Renal function during long-term follow-up after pediatric LT remained stable for the majority of our cohort. However, mild CKD was relatively common, warranting follow-up into adulthood. Although absolute tacrolimus exposure has a small depressing effect on concurrent GFR, there is no progressive deterioration of GFR due to long-term exposure, dose requirements or genetic background under the current target levels. These findings should be confirmed in a larger sample set, ideally including data from multiple centers.

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.

More than four decades of graft survival in pediatric kidney transplant recipients.

Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40years of graft survival currently alive with a functioning first graft. We reviewed all pediatric (age < 18years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions. We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0years (IQR: 43.1, 48.1)). The median age at transplant was 13.8years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30years, 67.7 (IQR: 63.2, 91.8); and at 40years, 80.3ml/min/1.73 m2 (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease). Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.

Renal Disease in Bangladesh Perspective

Bangladesh is one of the most densely populated areas in the world. Renal diseases are increasingly recognized and encompasses a large share of the health sector. About 20 million people are suffering from chronic kidney disease, and of them, approximately 35,000–40,000 develop endstage renal disease each year. Chronic glomerulonephritis, diabetes mellitus and hypertension are the principal causes of chronic kidney disease. Hypovolemia, sepsis, obstetric complications and drugs (including herbal and homeopathic remedies) are common causes of acute kidney injury. All three renal replacement therapy modalities (hemodialysis, peritoneal dialysis and renal transplantation) are performed in Bangladesh, yet only 25% of end-stage renal disease patients have access to treatment due to inadequate facilities and high healthcare costs. Nephrology as a specialty started its journey in 1973 in Bangladesh and now about 300 Nephrologists are managing the subject. Still there is huge need for more Nephrologists, as only one nephrologist is available for about every 0.8 million people. The country has improved financially from low- to low-middleincome country. Health sector is also more improving gradually. The government is now setting up renal care at rural level, introducing screening programs for early detection and prevention of kidney and other noncommunicable diseases. At the same time steps are under way to improve the advanced renal services at secondary and tertiary health institutes. Kidney transplantation started in 1982 and only live related transplantation are being done in several government and private organization. ABO-incompatible kidney transplantation has already been performed. Recently decease renal transplantation has also been performed. Research and training opportunities are expanding in collaboration with international organizations. Renal services appears up to date in this country but needs more and more enhancement to cope up the ever increasing burden.&#x0D; Bangladesh J Medicine 2023; 34(3): 180-185

Roles and practice of living-related lobar lung transplantation.

Living-donor lobar lung transplantation (LDLLT) was first performed in the USA and thereafter it was introduced in Japan in 1998 as an alternative modality to brain-dead donor lung transplantation (BDLT). Although the LDLLT procedure was employed for rapidly deteriorating patients who were hospitalized and mechanically ventilated at the time of transplantation, LDLLT demonstrated better or comparable post-transplant outcomes in comparison to BDLT. Less injured lobar grafts and a significantly shorter graft ischemic time possibly contributed to a significantly lower incidence of severe primary graft dysfunction (PGD) after LDLLT in comparison to BDLT. In standard LDLLT, patients obtained lobar grafts from two different donors, and thus most patients developed chronic lung allograft dysfunction (CLAD) only in the unilateral lung graft. This indicates that the contralateral unaffected lung graft could reserve lung function after the unilateral development of CLAD. In our transplant program, the incidence of CLAD per donor in LDLLT (14.4%) was also significantly lower in comparison to BDLT (24.7%). The 1-, 5- and 10-year survival rates after LDLLT were 90.9%, 75.5% and 57.2%, respectively, which were equivalent to those after BDLT (92.9%, 73.4% and 62.2%). The inherent surgical risk to the living donors should always be considered. In our experience, living-donor surgery was associated with a complication rate of 12.7%, and importantly, all living donors finally returned to their previous social lives. Precise functional and anatomical size matching between donor lobar graft and recipient could provide a favorable pulmonary function after LDLLT. We recently established multimodal surgical approaches, such as native upper lobe-sparing, right-to-left horizontally rotated, segmental, and single-lobe transplantation, in order to resolve the issue of size mismatch between the donor lobar graft and the recipient.

Bilateral living-related lobar lung transplantation avoiding bronchial stenosis associated with scoliosis by modified anastomosis: a case report

BackgroundSevere thoracic deformity caused by scoliosis often hampers lung transplantation (LTx) due to its underlying restrictive ventilatory dysfunction. Postoperative stenosis of the reconstructed bronchus due to spinal compression is also a complication after LTx in patients with scoliosis. Previous reports on LTx with scoliosis and its outcomes have not discussed the technical aspect of bronchial anastomosis. This report describes a case in which bronchial stenosis was avoided by modifying the angle of the right bronchial anastomosis.Case presentationA 26-year-old woman with atrial septal defect (ASD), pulmonary hypertension, Eisenmenger’s syndrome, and severe right scoliosis underwent bilateral living-related lobar LTx with her parents as donors followed by ASD closure. Left pneumonectomy and anastomosis preceded. On the right side, after pneumonectomy, the recipient’s right main bronchus was trimmed to rotate the bronchial anastomosis clockwise by 45°. This resulted in clockwise rotation of the graft (the lower lobe of the mother’s right lung), making axes of the graft and deformed vertebrae parallel. Postoperative bronchoscopy 2 months after surgery showed no evidence of compression or stenosis of the basal bronchial branch.ConclusionBy obliquely trimming the recipient’s right main bronchus to make the angle of the pulmonary graft and deformed thorax parallel, postoperative bronchial stenosis owing to severe scoliosis was successfully avoided.

Orthotopic living related donor transplantation of the liver right lobe in the treatment of unresectable bilobular liver metastases from colorectal cancer

Aim. Тo study the treatment result of unresectable liver metastases from colorectal cancer by the technique of transplantation. Case report. A man, born in 1963, applied to the Medical Center “Universal Clinic “Oberig” with a diagnosis of rectal adenocarcinoma pT3bN0M1 (hep) G2, synchronous colorectal liver metastases with multifocal bilobar lesions, stage IV after laparoscopic rectal extirpation and adjuvant FOLFIRI + Cetuximab polychemotherapy. Following a thorough examination of the patient, a decision was made to treat by transplanting a liver lobe graft donated by a living related donor (son). On April 12, 2022, the patient underwent orthotopic living related donor transplantation of the liver right lobe. In the early postoperative period, the patient developed an acute perforated ulcer of the small intestine, and he therefore was reoperated. The postoperative period was severe, but the condition stabilization was achieved with conservative treatment, and on the 38th postoperative day, the recipient was discharged from the hospital in a satisfactory condition. According to the control abdominal MRI during follow-up examinations, no signs of recurrence or progression were detected, however, 2 isolated metastatic foci in the lung parenchyma were detected bilaterally on the control CT scan of the chest 11 months after the liver lobe transplantation from the living related donor. Resection of metastatic foci was performed and systemic polychemotherapy was prescribed in that regard. Based on the control laboratory and instrumental examinations from 05.05.2023 (CT scan, MRI), there were no signs of the disease recurrence, the level of carcinoembryonic antigen was 1.5 ng/ml. Conclusions. Liver transplantation is an effective and radical method of treatment for patients with unresectable liver metastases from colorectal cancer. Transplantation using liver lobe from a living related donor in unresectable isolated liver metastases from colorectal cancer has advantages over all other methods and is safe for donors in highly specialized centers with sufficient experience in living related liver transplantation.

Socio-demographic Factors Affecting Health-related-quality of Life in Post-renal-transplant Patients

Objective: The objective of this study was to identify the socio-demographic factors affecting health related quality of life in renal transplant recipients. Material and Methods: A census of all registered post-renal-transplant patients was conducted from October 1, 2018, to January 31, 2019. Data were collected on a Kidney Disease Quality of Life questionnaire (SF-1.3) and analysed by Statistical Package for the Social Science (SPSS). Scores in the three main domains, physical component summary (PCS), mental component summary (MCS), and kidney disease component summary, were calculated. Mean scores for gender, type of donor, and employment were compared by unpaired t-test, while mean scores for age, level of education, and duration of transplant were compared by analysis of variance. Results: Out of 315 patients, 277 (87.9%) were males and 38 (12.1%) were females. The mean age was 37.26 (±10.14) years. Live unrelated transplants were 58.41% while live related transplants were 41.58%. Males had a significantly higher average (p-value=0.001) PCS score, but females had significantly higher average (p-value=0.05) MCS score. There was variation with respect to the PCS (p-value=0.031) and MCS (p-value=0.001) scores in the different age categories. The education groups varied significantly with respect to MCS (p-value=0.05). The recipients of live unrelated transplants had significantly lower average PCS score. Conclusion: The female gender, live related donor and variations in ages were associated with lower PCS scores, while male gender, variations in ages, and education were associated with lower MCS scores. This study demonstrates that the Kidney Disease Quality of Life Short Form-1.3 (KDQOL SF-1.3) is a good tool to reveal differences in HRQOL scores in renal transplant recipients.

Utilizing ultra-small volume graft in auxiliary liver transplantation for portal hypertension

Objective: To examine the clinical effect of auxiliary liver transplantation with ultra-small volume graft in the treatment of portal hypertension. Methods: Twelve cases of portal hypertension treated by auxiliary liver transplantation with small volume graft at Liver Transplantation Center,Beijing Friendship Hospital, Capital Medical University between December 2014 and March 2022 were studied retrospectively. There were 8 males and 4 females,aged 14 to 66 years. Model for end-stage liver disease scores were 1 to 15 points and Child scores were 6 to 11 points. The grafts was derived from living donors in 9 cases,from split cadaveric donors in 2 cases,from whole cadaveric liver of child in 1 case. The graft recipient body weight ratios of 3 cadaveric donor livers were 0.79% to 0.90%, and of 9 living donor livers were 0.31% to 0.55%.In these cases, ultra-small volume grafts were implanted. The survivals of patient and graft, complications, portal vein blood flow of residual liver and graft, abdominal drainage and biochemical indexes of liver function were observed. Results: All the grafts and patients survived. Complications included outflow tract torsion in 2 cases, acute rejection in 1 case, bile leakage in 1 case, and thyroid cancer at the later stage of follow-up in 1 case, all of which were cured. The torsion of outflow tract was attributed to the change of anastomotic angle after the growth of donor liver. After the improvement of anastomotic method, the complication did not recur in the later stage. There was no complication of portal hypertension. The measurement of ultrasonic portal vein blood flow velocity showed that the blood flow of residual liver decreased significantly in the early stage after operation, and maintained a very low blood flow velocity or occlusion in the long term after operation, and the blood flow of transplanted liver was stable. Conclusions: Auxiliary liver transplantation can implant ultra-small donor liver through compensation of residual liver. This method may promote the development of living donor left lobe donation and split liver transplantation. However, the auxiliary liver transplantation is complex, and it is difficult to control the complications. Therefore, this method is currently limited to centers that are skilled in living related liver transplantation and that have complete ability to monitor and deal with complications.

Would a 6-Month Wait Time for Patients With Hepatocellular Carcinoma Improve Organ Allocation in Centers With Active Living Related Liver Transplant Activity?

The Model for End-Stage Liver Disease score is used to prioritize patients awaiting liver transplant. Since hepatocellular carcinoma does not affect the score, patients with hepatocellular carcinoma are given exception points to promote fairness. In the United States,this practice has resulted in overcorrection; hence, a 6-month delay to grant exceptions was implemented. A similar flaw may exist in Saudi Arabia. We retrospectively reviewed data for 214 adults listed for liver transplant from January 2016 to July 2020 at King Abdulaziz Medical City, Riyadh. Data included diagnoses, Model for End-Stage Liver Disease scores, wait times, and outcomes. Comparative analyses were performed to contrast patients with hepatocellular carcinoma versus patients without hepatocellular carcinoma. Mean age was 55.2 ± 11.6 years, and 61% were male patients. Outcomes were that the patient received a transplant(77%; n = 165/214), dropped out (18%; n = 38/214), or remained on the wait (5%; n = 11/214). Of the hepatocellular carcinoma group, 84% (n = 56/68) received transplant versus 74% (n = 108/146) in the control group (P = .11). There was no significant difference in dropout rates (P = .33). Patients with hepatocellular carcinoma constituted 32% (n = 68/214) ofthe waitlist, yetthey received 40% of deceased organ offers (P = .015). Most patients in the hepatocellular carcinoma group received pretransplant bridging therapy for a median of 166 days (101-329.5 days). Median time from listing to transplant was shorter for the control group, 57 days versus 148 days (P < .001). Long-term outcomes were comparable between both groups. This study suggests that implementation of the 6-month wait time for patients with hepatocellular carcinoma before granting exception points may not be necessary for active living related liver transplant programs. Nevertheless, this remains a sound strategy to follow.

Acquired diaphragmatic hernia in a child with a related liver transplant

Acquired diaphragmatic hernia in children is rare. Even less often, this disease occurs after liver transplantation for biliary atresia. In our case, diaphragmatic hernia was acquired, since the patient underwent repeated chest X-ray examinations including CT prior to liver transplantation. There were no signs of hernia. Clinical manifestations of diaphragmatic hernia were absent throughout 9 months after liver transplantation and manifested acutely with combination of symptoms of respiratory failure and intestinal obstruction. Surgical treatment was performed after emergency consultation with attending doctor.

Living related liver transplantation in the Republic of Uzbekistan: current status and development prospects

To analyze primary results of living related liver transplantation in the Republic of Uzbekistan. There were 44 living related transplantations of the right liver lobe in patients with decompensated liver failure between February 2018 and February 2023. Uneventful postoperative period was observed in 17 (38.6%) recipients. Other 27 patients (61.4%) developed 47 various postoperative complications (1-3 events per a patient). Of these, 8 (18.2%) patients required early postoperative re-laparotomy. Among 44 patients, 9 (20.5%) ones died in early postoperative period, and one patient died in long-term period (3 years after transplantation) from chronic rejection under refusal to take immunosuppressive drugs. Early satisfactory results were obtained in 79.5% of patients, long-term favorable outcomes - in 77.3% of cases. Engraftment rates and survival of recipients to a large extent depend on surgical strategy, baseline disease and clinical severity. The so-called "center effect" is essential at initial stages of implementation of the program.

Complications and mortality in cirrhotic children awaiting liver allografts: a single-center report from Iran

Liver transplantation (LT) is the treatment of choice for end-stage liver disease in children, but donor shortage is still a central problem in this age group. Objective. To evaluate the rate of complications and mortality in cirrhotic children awaiting transplantation. Patients and methods. We analyzed medical records of 113 children under 18 years of age who were listed for LT, but the organ was unavailable between 2013 and 2018. The outcome was assessed from their records or follow-up data. Results. Among the children (mean age: 3.79 years; 50.4% boys and 49.6% girls) awaiting LT, the common causes of cirrhosis were biliary atresia (38.9%) and progressive familial intrahepatic cholestasis (17.7%). While awaiting transplantation, 82 (72.6%) children died. The most common complications were encephalopathy (34.5%), esophageal bleeding (26.5%), infections (23.0%), and spontaneous bacterial peritonitis (13.3%). The mean duration of hospital admission was 2.72 ± 3.10 days. Conclusion. About two-thirds of children listed for LT developed complications, and about three-quarters died without any LT. It seems that split liver transplantation and the introduction of a live-related transplant program in our center will provide many benefits to pediatric patients. Key words: liver transplantation, mortality, cirrhosis, pediatrics, children

The role of herpesviruses and pneumocysts in infectious complications in children during liver transplantation

Infections occupy one of the central places among the complications of transplants. The frequency of fatal infectious complications during the first twelve months after transplantation ranges from 2.6 to 51.7%. Identifying markers of opportunistic infections before transplantation will help reduce the likelihood of developing these infections after induced immunosuppression. The aim of the study was to study the role of herpesviruses and pneumocysts in the occurrence of infectious complications in children before and after liver transplantation based on the detection of markers of a number of herpesvirus infections and pneumocystosis. The article presents the results of a comprehensive examination for markers of herpesvirus infections and pneumocystosis of 70 children who were treated at the Shumakov Transplantation Research Center. It should be noted that 55 patients (78.6%) were diagnosed with infectious complications, of which 46 people (65.7%) had pneumonia. To detect IgM and IgG antibodies to herpesviruses and pneumocysts, peripheral blood serum samples were examined by enzyme immunoassay (ELISA). Detection of common HBV antigens was carried out by indirect immunofluorescence reaction (NRIF). Early antigens and reproduction of herpesviruses were detected by rapid culture method (BCM) on Vero and M-19 cell cultures for CMVI. In the event of infectious complications (pneumonia) in children who underwent related liver transplantation, the number of patients with active EBI markers increased almost 7 times and active HCV-6 markers increased 3.5 times. The paper shows the need for a broader laboratory screening of opportunistic infections, which will serve to achieve better clinical results, contribute to the formation of more advanced diagnostic algorithms, as well as improve epidemiological surveillance of these infections.

S3207 Vanishing Tacrolimus Syndrome

Introduction: Cellular rejection is common and therapeutic IS levels are needed to minimize this risk. This case stresses the need to fully explore, and potentially reexplore common causes of subtherapeutic IS levels. Case Description/Methods: A 38-year-old man with history of alcohol related cirrhosis and liver transplant in 2019. followed by 2 episodes of acute rejection, presented with significantly abnormal liver tests. Tacrolimus levels were undetectable and liver biopsy showed moderate rejection. After a course of IV steroid, he was started on prednisone, sirolimus, and increased doses of tacrolimus. Tacrolimus levels remained undetectable despite escalating doses, and addition of fluconazole– used for cytochrome (CYP) inhibition. Liver tests worsened after initial improvements, and repeat biopsy showed changes of chronic rejection. He was treated with a 5-day course of anti-thymocyte globulin, steroids, and maintained on increased immunosuppression (IS). Drug levels for tacrolimus, sirolimus, and mycophenolate were undetectable. He reported medication adherence, and undetectable tacrolimus levels were thought to be due to CYP metabolism. With this concern, he was started on azathioprine and belatacept infusions for IS. He was readmitted with abdominal pain and chronic 10-15 stools daily. Physical exam was notable for abdominal pain, no jaundice or asterixis. Labs showed WBC 5.7, INR 1.03, total bilirubin 11.9, AST 784, ALT 714, Alkaline phosphatase 538, albumin 3.5, negative serology for EBV, CMV, and HSV, and tacrolimus level < 1.0. Lab testing for diarrhea was negative for viral and bacterial causes. With concern for malabsorption, IV tacrolimus was started. EGD and colonoscopy with biopsies were negative for malabsorptive pathology. He was started on pancreatic enzymes for concerns of pancreatic insufficiency, and fecal elastase obtained after was elevated. After 24 hours of IV tacrolimus, serum level was 22.7, and continued to rise even after reduction of dosing suggesting malabsorption as cause of subtherapeutic IS. Discussion: Therapeutic IS levels are vital for transplant success, with an understanding that this needs effective absorption and metabolism. Our patient failed to have therapeutic levels since shortly after his transplant– despite previous negative lab and endoscopic evaluations for malabsorption. We used tactics focused on abnormal metabolism, however, resultant drug levels after IV tacrolimus shows the importance of considering malabsorption as barriers to achieving therapeutic IS.

P9.26: Management of Post Liver Transplantation-Tacrolimus Induced Toxicity With Normal Serum Levels

Introduction: Drug induced liver injury post liver transplantation occurs in 1.7% of the patients. Tacrolimus being an effective immunosuppressant is used to treat acute rejection. However, it rarely can cause toxicity which is demonstrated by cholestatic liver injury. We hereby present the case of a young male, who was a diagnosed case of Wilson’s disease, on pencillamine chelating therapy and underwent living related liver transplantation. Case: Within a month post transplantation he developed deranged, predominantly cholestatic pattern liver function tests. Laboratory parameters showed Total bilirubin 1.12mg/dl, ALT 553 IU/L Gamma-glutamyl transferase 624 IU/L and Tacrolimus level of 10.2ng/ml. After thorough evaluation liver biopsy was performed. Liver biopsy documented hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. Although with normal level of Tacrolimus, biopsy was suggestive of drug induced liver injury. Thus, Tacrolimus dose was reduced, which resulted in improvement of his LFTs and was later discharged. Conclusion/ Discussion: We have demonstrated tacrolimus induced toxicity in liver transplant recipients, despite normal serum levels. Thus, transplant physicians should keep high index of suspicion regarding toxicity in post-transplant setting. Tacrolimus is an effective post liver transplantation immunosuppressant and has the ability to treat early acute rejection. Liver biopsy documented hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. Cholestatic liver injury after tacrolimus usually resolves after dose reduction or by switching to another agent.

333.2: Vascular Complications in Pediatric Liver Transplants And Their Management

Introduction: Unlike other organs, the blood supply of the liver occurs through two systems. One of these is the hepatic artery, and it supply approximately one-third to one-fifth of the liver. The rest of the liver is supplied with blood via the portal vein. The outflow of blood circulation in the liver is via the hepatic veins. Any disruption in this blood circulation results in deterioration in liver functions. In this study, we aimed to evaluate early vascular complications in pediatric liver transplants. Methods: From 8 November 1988 to 31 December 2021, we performed 701 LT procedures and 334 of them were pediatric.). We reviewed the medical records of these recipients for the following: primary cause of liver failure, age, and weight at the time of transplantation, type of graft, vascular complications and their management. One hundred and seventy six of the recipients were male and 158 were female. Mean age of 7.34 years (0.5 months – 17 years). Nineteen (5.7%) of the LT were deceased donor LT and 315 (94.3%) were living related liver transplant. Most cause of liver failure was biliary atresia (n=169). Mean weight of recipients was 23.3 kg. Most of graft types was left lateral graft (n=204) Results: Hepatic vein complications occurred in 3 patients. In all three patients, stenosis was detected in the portal vein anastomosis region and was successfully treated with interventional radiological methods by placing a stent in the anastomosis region. Portal vein complications occurred in 3 patients. In one of these patients, hemostasis was performed by surgical method due to bleeding from the portal vein anastomosis. In the second patient, the anastomosis was surgically revised due to thrombus formation in the portal vein. In the third patient, due to a stenosis of more than 50% in the portal vein anastomosis, a stent was placed in the anastomosis region after balloon dilation using interventional radiological methods, and blood flow was successfully maintained. Hepatic artery complications occurred in 54 patients. Hepatic artery thrombosis occurred in 31 patients, hepatic artery stenosis in 13 patients, bleeding from hepatic artery anastomosis in 7 patients, hepatic artery dissection in 2 patients, and pseudoaneurysm in the hepatic artery in 1 patient. 43 of these patients were successfully treated with interventional radiological methods and 11 of them surgically. Conclusion: Vascular complications seen in liver transplants can cause deterioration in hepatic functions and acute liver failure. Especially hepatic artery complications are one of the most important causes of biliary tract complications that will develop in the future. Vascular complications can be successfully treated at an early stage in experienced organ transplant centers.

Living-Related Liver Retransplantation in a Child: When it Seems Impossible (A Clinical Case)

The objective: to show the possibility of anesthesia during liver retransplantation in a child in the absence of adequate vascular access.A clinical case of liver retransplantation in a 10-year-old patient with liver transplant dysfunction and acquired thrombophilia is considered. In 2011, the child underwent Kasai portoenterostomy, and in 2012, living-related transplantation of the left lateral liver bisegment from a related donor was performed due to liver cirrhosis as an outcome of biliary atresia. Also, the child had multiple surgical interventions due to perforations of the small intestine with underlying segmental venous mesenteric thrombosis. In the long term after the transplantation, irreversible transplant dysfunction developed with manifestations and worsening of hepatocellular insufficiency, encephalopathy, as well as recurrent bleeding from varicose veins of the esophagus and cardiac orifice. The clinical situation was complicated by the lack of adequate vascular access due to total thrombosis of the venous system, thrombosis of the superior and inferior vena cava. The only possible option for ensuring adequate venous access was the implantation of a tunneled catheter into the right atrium of the right atrium for prolonged standing in conditions of single-lung ventilation through right-sided thoracotomy.

Obligation and the “Gift of Life”: Understanding frictions surrounding advance care planning and goals of care discussions in liver transplantation

PurposeThis article examines the contradictions at play in advance care planning and goals of care discussions in liver transplantation settings. Focusing on code status, we ask why these important conversations are controversial in the transplant context, and why “full code” is the norm for those listed for liver transplantation. Basic proceduresThis article uses a composite case comprising the authors’ clinical experiences to examine the frictions that surround advance care planning in the context of liver transplant. The authors situate this composite case to related ethnographic and liver transplantation literature. Main findingsOur experience of difficulties for clinical teams in reconciling patients’ requests for a do not resuscitate order with their commitment to liver transplantation is borne out in the liver transplant literature in this area. We argue that the high expectations of patients, families, the treatment team, and society in relation to transplant translate into an obligation for patients to have full code status for their desire for transplantation to be recognized fully. We relate this analysis to work on the “transplant imperative” Santivasi et al. describe. ConclusionsSolid organ transplant is often represented as a “cure” or “new beginning.” This future-orientation of solid organ transplantation is incorrectly considered at odds with patients’ request for do not resuscitate orders. Challenging the norms embedded in notions of cure can afford patients to greater agency over their lives and bodies, while affirming that disabled lives are valued.