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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

Improved survival in children with HPS: Experience from two high volume liver transplant centers across continents.

BACKGROUND: Severe HPS increases morbidity and mortality after LT in children. We reviewed the combined experience of LT for HPS in children from two LT centers in Europe and Asia. METHODS: All children with "proven" HPS as per ERS Task Force criteria (detailed in manuscript) who underwent LT were categorized into M (PaO2 ≥80 mmHg), Mo (PaO2  = 60-79 mmHg), S (50-59 mmHg), and VS (PaO2 <50 mmHg) HPS, based on room air PaO2 . RESULTS: Twenty-four children with HPS underwent 25 LT (one re-transplantation) at a median age of 8 years (IQR, 5-12), after a median duration of 8 (4-12) months following HPS diagnosis. Mechanical ventilation was required for a median of 3 (1.5-27) days after LT. Ten children had "S" post-operative hypoxemia, requiring iNO for a median of 5 (6-27) days. "VS" category patients had significantly prolonged invasive ventilation (median 35 vs. 3 and 1.5 days; p = .008), ICU stay (median 39 vs. 8 and 8 days; p = .007), and hospital stay (64 vs. 26.5 and 23 days; p < .001) when compared to "S" and "M/Mo" groups, respectively. The need for pre-transplant home oxygen therapy was the only factor predicting need for re-intubation. Patient and graft survival at 32 (17-98) months were 100% and 95.8%. All children ultimately had complete resolution of HPS. CONCLUSIONS: VS HPS is associated with longer duration of mechanical ventilation and hospital stay, which emphasizes the need for early LT in these children.

Delayed Expulsion of biliary cast after hepaticojejunostomy for post-liver transplantation biliary stricture-better cut than canulate?

BACKGROUND: Biliary strictures after living donor liver transplantation (LDLT) are a significant cause of post-transplant morbidity. Endoscopic therapy is usually the first choice of treatment though surgical treatment may provide better biliary drainage. METHODS: We report a case of LDLT performed in a child for acute liver failure who developed an anastomotic biliary stricture with biliary cast formation. We performed a Roux en Y hepaticojejunostomy to treat the stricture. RESULTS: Allograft function improved after surgery with no further episodes of cholangitis. Two months after the surgery, the child passed a large biliary cast in the stools. This reiterates the advantage of wide biliary drainage provided through surgical therapy. CONCLUSIONS: Surgery for biliary strictures following LDLT may provide superior long term biliary drainage- especially when biliary casts are present.

Therapeutic Plasma Exchange for Management of Early Allograft Dysfunction After Living Donor Liver Transplant: An Unmatched Cohort Study.

OBJECTIVES: Therapeutic plasma exchange has been reported to be useful in the management of acute liver failure and acute-on-chronic liver failure. This retrospective study evaluated therapeutic plasma exchange as an adjunct to standard supportive care for early allograft dysfunction after living donor liver transplant. MATERIALS AND METHODS: All consecutive adult living donor liver transplants performed from January 2015 to February 2019 were included. Patients treated without or with therapeutic plasma exchange for early allograft dysfunction (Olthoff criteria) were compared. RESULTS: There were 465 adult transplant recipients, and 67 (14.4%) had early allograft dysfunction, of which 43 (64%) had therapeutic plasma exchange and 24 (36%) did not. Fourteen patients were excluded, as they had both preoperative and immediate postoperative therapeutic plasma exchange (5 patients with acute liver failure and 9 with acute-on-chronic liver failure). The therapeutic plasma exchange group (n = 29) had more preoperative acute kidney injury (55.2% vs 25.0%; P = .009), lower graft-recipient weight ratio (0.96 vs 1.09; P = .043), and slightly higher final portal pressure (11 vs 10 mg/dL; P = .027). Therapeutic plasma exchange was started at a median of postoperative day 9, with median serum bilirubin of 13.6 mg/dL and a median of 3 sessions per patient. There was no 90-day mortality in the group without therapeutic plasma exchange; however, in the therapeutic plasma exchange group, 13 patients (45%) died (P < .001). Patients who received therapeutic plasma exchange had more septic complications (62.1% vs 12.5%; P < .001) and needed more postoperative renal replacement therapy (51.7% vs 8.3%; P < .001). CONCLUSIONS: This is the first study to compare patients treated with or without therapeutic plasma exchange for early allograft dysfunction in the living donor liver transplant setting. Within the limitations of this retrospective study, we were unable to confirm whether therapeutic plasma exchange could increase early mortality.