Current Status and Outcomes of Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Results From a Multicenter Retrospective Study Over Two Decades.

BACKGROUND: Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era. METHODS: We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared. RESULTS: The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002). CONCLUSIONS: The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.

Auxiliary Partial Orthotopic Liver Transplantation Is a Safe and Effective Option for Yellow Phosphorus Toxin-induced Acute Liver Failure.

BACKGROUND: Ingestion of yellow phosphorus-containing rodenticides (YPR) or firecrackers is an important cause of acute liver failure (ALF) in young adults and children, particularly in South and South-East Asia and South America. Emergency liver transplantation is indicated in cases refractory to intensive supportive therapy, including low-volume plasma exchange. There are no published reports on the feasibility of auxiliary partial orthotopic liver transplantation (APOLT) for YPR-induced ALF. METHODS: Clinical details of patients undergoing APOLT for YPR-induced ALF in 1 unit are reported. Details of postoperative follow-up, native remnant regeneration, and immunosuppression withdrawal are also reported. RESULTS: Between January 2021 and December 2023, 3 patients (4 y, 1.5 y, and 26 y) underwent emergency living donor liver transplantation for YPR-induced ALF. All patients were refractory to supportive therapies, including therapeutic plasma exchange, and demonstrated progression of liver injury in the form of severe encephalopathy needing intubation, ventilation, and organ support. APOLT was considered because of their young age and minimal intraoperative inotropic requirement. All explants showed confluent parenchymal necrosis with microvesicular and macrovesicular steatosis. Patients were initially maintained on standard immunosuppression. Good remnant regeneration was noted on follow-up imaging in all cases, enabling gradual withdrawal of immunosuppression. Currently, 1 child has been off immunosuppression for 15 mo and 2 others are on reduced doses of immunosuppression. All patients demonstrated good liver function. CONCLUSIONS: APOLT procedure can be an appropriate transplant option in YPR-related ALF for children and young adults without severe hemodynamic instability.

A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

An international survey of venous thromboembolic events and current practices of peri-operative VTE prophylaxis after living donor hepatectomy.

BACKGROUND: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy . The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. METHODS: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri-operative thromboembolic prophylaxis and an audit of -perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016-2020). RESULTS: Fifty-one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016-2020. All centers included pre-operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual-mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post-operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. CONCLUSION: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence-based guidelines regarding risk assessment, and peri-operative prophylaxis are needed.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Overview of hepatocellular carcinoma: from molecular aspects to future therapeutic options.

Hepatocellular carcinoma (HCC) is the seventh most highly prevalent malignant tumor globally and the second most common cause of mortality. HCC develops with complex pathways that occur through multistage biological processes. Non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, alcoholic liver disease, autoimmune hepatitis, hepatitis B, and hepatitis C are the causative etiologies of HCC. HCC develops as a result of epigenetic changes, protein-coding gene mutations, and altered signaling pathways. Biomarkers and potential therapeutic targets for HCC open up new possibilities for treating the disease. Immune checkpoint inhibitors are included in the treatment options in combination with molecular targeted therapy.

Novel radiological technique to recognize acute liver failure caused by yellow phosphorous containing rodenticides.

Yellow phosphorous rodenticide (YPR) poisoning is the commonest cause for acute liver failure (ALF) in southern and western India. Due to medicolegal issues, history of YPR ingestion may not be available. As early recognition of YPR poisoning is important and there are no specific biochemical assays, other early predictors to identify this entity is necessary. We evaluated the diagnostic role of plain computed tomography (CT) in identifying YPR-induced ALF. All patients admitted to the liver unit with a diagnosis of ALF underwent a plain CT scan abdomen. Demographic details, clinical history, laboratory parameters, liver attenuation index (LAI) calculated on CT scan, treatment details, need for liver transplantation and clinical outcome were analyzed. Parameters for YPR-induced ALF (ALF-YPR) and other causes (ALF-OTH) were compared. Ability of LAI to distinguish ALF-YPR and ALF-OTH was analyzed using receiver operating characteristic (ROC) curve analysis. Twenty-four patients (15 female [62.5%]) were included in the study. Thirteen patients (54%) had YPR poisoning, while the rest formed the ALF-OTH group (11,46%). ALF-YPR patients had higher transaminase levels, lower peak serum bilirubin levels. ALF-YPR livers had significantly lower LAI as compared to ALF-OTH (- 30 vs. - 8, p = 0.001). On ROC curve analysis, an LAI greater than - 18 ruled out YPR as the cause for ALF with 91% sensitivity and 85% specificity. On regression analysis, LAI was the only independent factor predicting ALF-YPR (odds ratio - 0.86, [0.76, 0.96] p = 0.008). Our data shows that LAI on plain abdominal CT scan can be used to quickly recognize ALF-YPR in unclear cases so that necessary treatment protocol can be activated, or patient transfer arranged. Our analysis shows that an LAI greater than - 18 can reliably rule out YPR ingestion as the cause for ALF.

Pediatric combined living donor liver and kidney transplantation for primary hyperoxaluria type 2.

We report the case of a 12-year-old boy with primary hyperoxaluria type 2 (PH2) presenting with end-stage renal disease and systemic oxalosis who underwent a combined living donor liver and kidney transplant from 3 donors, 1 of whom was a heterozygous carrier of the mutation. Plasma oxalate and creatinine levels normalized immediately following the transplant and remain normal after 18 months. We recommend combined liver and kidney transplantation as the preferred therapeutic option for children with primary hyperoxaluria type 2 with early-onset end-stage renal disease.

Right Lobe Living Donor Hepatectomy in the Setting of Agenesis of Gall Bladder - A Case Report.

Agenesis of Gall Bladder (AGB) is a rare congenital anomaly with only around 500 cases reported so far. The condition may be associated with other biliary anomalies and present diagnostic and technical challenges during hemi hepatectomy which can be surmounted with careful planning. Live donor hepatectomy in the setting of AGB has not been reported before. We report a case of AGB in a potential living donor and highlight the technical modifications used to perform a safe right hepatectomy in this donor.

Newly proposed classification of celiac artery variations based on embryology and correlation with computed tomography angiography.

Purpose: We studied the prevalence of celiac trunk and its anatomical variations on diagnostic computed tomography angiography (CTA) studies and have proposed a new classification to define the celiac artery (CA) variations based on embryology. Material and methods: We retrospectively assessed the celiac trunk variations in 1113 patients who came to our department for diagnostic CTA for liver and renal donor workup. The patient data were acquired from the Picture Archiving and Communication System of our institutions. We analysed the celiac trunk's origin and branching pattern, including the superior mesenteric artery (SMA) and inferior phrenic artery (IPA). Results: We evaluated the CTA studies of 1050 patients. A normal trifurcation pattern, the most common type, was observed in 39% of cases. Variation with CA + left IPA was the most common subtype. Other variations noted in the study and their incidences are listed in the table below. We attempted to propose a new classification based on embryo-logy, which comprises 6 main types and their subtypes. We also analysed previous studies from the literature, including cadaveric, post-mortem, CTA, and digital subtraction angiography studies and compared them with the present study. Conclusions: Because variations of CA classifications reported to date do not encompass all CA branching pattern variants, we have proposed a new classification that incorporates most of the variants. We reiterate the clinical importance of anatomical variants of CA, IPA, and SMA in surgical and interventional radiology procedures.

Neurological complications in pediatric liver transplant recipients.

INTRODUCTION: There is paucity of data on neurological complications (NCs) and its predisposing factors, in pediatric liver transplant (PLT) recipients. METHODS: Records of seventy-one children who underwent LT between October 2018 and November 2019 were reviewed. Patients were categorized into group A: with NC and group B: without NC in the post-LT period. Various risk factors contributing to NC were studied. RESULTS: In total, 15 (21.1%) had NC (group A) and 56 (78.9%) had no NC in the post-LT period. NC included cerebrovascular accident (n = 1), seizures (n = 5; 4 generalized, 1 focal), central pontine myelolysis (CPM) (n = 1), diaphragmatic palsy (n = 2), peripheral neuropathy (n = 1), extrapyramidal movements (n = 3), and encephalopathy beyond 96 h (n = 2). The median onset of NC was at 8.5 days post-LT (1-58 days). Ten (66.7%) patients in group A had grades 2-4 hepatic encephalopathy (HE) prior to LT. Eight (14.3%) patients in group B also had pre-LT neurological issues including HE in six, epilepsy and spastic diplegia in one each. On univariate analysis, pre-existing HE, high PELD/MELD score, pre-LT ventilation, pre-LT infection, higher day 1 post-operative bilirubin (all p < .05), and higher tacrolimus were found to predict post-operative NC whereas on multivariate analysis, pre-LT HE was the only predictive factor. Median follow-up was 15.5 months. Four patients died in each group (survival log-rank p = .369). All the surviving patients in group A (n = 11) fully recovered from the NC. CONCLUSION: Pre-transplant HE was the single most significant predisposing factor for post-LT neurological complications.

Hilar Fibropolycystic Liver Disease of Unknown Etiology: A Revelation from the Explant Liver.

Fibropolycystic diseases of the liver comprise a spectrum of disorders affecting bile ducts of various sizes and arise due to an underlying ductal plate malformation (DPM). We encountered a previously unreported variant of DPM, the hilar fibropolycystic disease which we diagnosed in the explant liver. A 2-year-old boy was referred for liver transplantation with a diagnosis of biliary atresia (BA) and failed Kasai portoenterostomy (KPE). He had cirrhosis with portal hypertension along with synthetic failure indicated by coagulopathy and hypoalbuminemia. The child underwent liver transplant successfully. The explant liver had fibropolycystic disease confined to the perihilar liver and hilum. No pathogenic mutation was detected by whole exome sequencing. Fibropolycystic liver disease may represent a peculiar anatomical variant, which can be diagnosed by careful pathological examination of the explant liver. The neonatal presentation of hilar fibropolycystic liver disease can be misdiagnosed as BA.

Adipose tissue derived stromal cells in a gelatin-based 3D matrix with exclusive ascorbic acid signalling emerged as a novel neural tissue engineering construct: an innovative prototype for soft tissue.

The current study investigated a triad, which comprises of adipose tissue derived stem cells isolated from infrapatellar fat pad and gelatin/polyvinyl alcohol (PVA)-based matrix with exclusive ascorbic acid signalling. Though, the bio-mechanical properties of the gelatin-PVA blended scaffolds in wet condition are equivalent to the ECM of soft tissues in general, in this study, the triad was tested as a model for neural tissue engineering. Apart from being cytocompatible and biocompatible, the porosity of the scaffold has been designed in such a manner that it facilitates the cell signalling and enables the exchange of nutrients and gases. The highly proliferative stem cells from Passage 2 were characterized using both, mesenchymal and embryonic stem cell markers. As an initial exploration the mesenchymal stem cells at Passage 4 were exposed to ascorbic acid and basic fibroblast growth factor signalling for neuronal differentiation in 2D environment independently. The MSCs successfully differentiated and acquired neuron specific markers related to cytoskeleton and synapses. Subsequently, three phases of experiments have been conducted on the 3D gelatin/PVA matrix to prove their efficacy, the growth of stem cells, growth of differentiated neurons and the in situ growth and differentiation of MSCs. The scaffold was conducive and directed MSCs to neuronal lineage under specific signalling. Overall, this organotypic model triad could open a new avenue in the field of soft tissue engineering as a simple and effective tissue construct.

When Push Comes to Shove! Emergency ABO-Incompatible Pediatric Living Donor Liver Transplant for Acute Wilson's Disease.

ABO-incompatible living donor liver transplantation (ABOi-LDLT) is on the rise as a viable option in countries with limited access to deceased donor grafts. While reported outcomes of ABOi-LT in children are similar to ABO- Compatible liver transplant (ABOc-LT), most children beyond 1-2 years of age will need desensitization to overcome the immunological barrier of incompatible blood groups. The current standard protocol for desensitization is Rituximab that targets B lymphocytes and is given 2-3 weeks prior to LT. However, this timeline may not be feasible in children requiring emergency LT for acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). In this emergency situation of ABOi-LT, a safe multipronged approach may be an acceptable alternative solution. We report a child with acute Wilson's disease with rapidly deteriorating liver function who underwent a successful ABOi-LDLT using a rapid desensitization protocol.

Viscoelastic Monitoring in Liver Transplantation.

Cirrhosis and liver transplantation (LT) surgery are associated with substantial alterations to the patient's coagulation status. Accurate monitoring of these changes during LT can help manage bleeding proactively and potentially reduce transfusion requirements. Unlike conventional coagulation tests (CCTs), viscoelastic monitoring (VEM) can provide an accurate, real-time, point-of-care assessment of coagulation status during LT and hence has become an invaluable tool for anesthetists and intensive care physicians. However, it remains an enigmatic subject for transplantation surgeons who are more conversant with CCTs. This review discusses the principles of VEM, provides a primer to understanding and interpreting its output, and explains how it can be used to make real-world clinical decisions during LT.

Erratum: Hilar Fibropolycystic Liver Disease of Unknown Etiology: A Revelation from the Explant Liver.

[This corrects the article DOI: 10.1055/s-0040-1716829.].

Liver Transplantation: A Safe and Definitive Alternative to Lifelong Nitisinone for Tyrosinemia Type 1.

OBJECTIVES: To report the experience of liver transplantation (LT) for tyrosinemia type 1 (TT-1). METHODS: Clinical data of children with TT-1 who underwent living donor LT between July 2009 and May 2020 were retrospectively analyzed. Data included pre-LT nitisinone therapy, graft type, post-LT complications, HCC incidence, and graft/patient survival. RESULTS: Nine children were diagnosed with TT-1 at a median age of 12 mo (6-54 mo). Nitisinone was started in 6 patients at a median age of 15 mo (6-42 mo), but all had frequent interruption of therapy due to logistics with drug procurement including its cost. Median age at transplantation was 5 y (2-11 y). Explant liver showed HCC in 5 patients (55% of total cohort). The graft and patient survival are 100% with median follow-up of 58 mo (24-84 mo). CONCLUSION: LT is curative for TT-1 and excellent results can be obtained in experienced centers. This is especially favorable in countries with limited resources where the cost of medical therapy is highly prohibitive, with lifelong diet restrictions and unclear long-term risk of HCC.