Youngest Living Donor Liver Transplant for End-Stage Liver Disease in a 6-Month-Old With a Novel Aggressive Mutation in KIF12 Gene.

BACKGROUND: Kinesin family member 12 (KIF12) mutation-related cholestatic disorder represents a rare subtype of progressive familial intrahepatic cholestasis (PFIC), referred to as PFIC Type 8, with only 21 reported cases globally to date. METHODS: Here, we present a unique case of a 6-month-old boy diagnosed with homozygous KIF12 gene mutation, who successfully underwent a living donor liver transplant at our center for end-stage liver disease. RESULTS: This case marks the youngest patient of KIF12-related cholestatic disorder necessitating a liver transplant to date. The child initially presented with neonatal cholestasis and then developed infantile hepatic decompensation. Our report discusses the diagnostic process and management strategies employed. It underscores the importance of prompt diagnosis through clinical suspicion, biochemical parameters, and genetic testing, as well as the adoption of suitable management strategies, including the early contemplation of liver transplant in such exceptional and rare cases of genetic intrahepatic cholestasis. CONCLUSION: KIF12-related genetic disease should be considered in neonatal cholestasis cases with high gamma glutamyl transpeptidase to differentiate from conditions like biliary atresia. Favorable outcomes post liver transplant stress the importance of early genetic testing and referral to liver transplant centers for unresponsive patients, potentially saving lives.

Domino liver transplantation for maple syrup urine disease in children: A single-center case series.

BACKGROUND: Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. METHODS: It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. RESULTS: Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. CONCLUSION: DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.

Safety and feasibility of immediate tracheal extubation of small pediatric patients after living donor liver transplantation.

BACKGROUND: Immediate extubation is integral constituent of enhance recovery protocols. Purpose of this study was to examine success rates and safety of protocolized immediate extubation in pediatric living donor liver transplant recipients and to find out factors associated with non-immediate extubation in operation room. METHODS: We performed retrospective analysis for data of small (≤20 kg) pediatric patients transplanted between 2017 and 2019 (protocolized duration) and compared with data of transplants done between 2014 and 2016 (non-protocolized duration). Further, we compared data during each time duration between immediate extubation and non-immediate extubation group to find risk factors in that particular duration. RESULTS: Immediate extubation rates were significantly higher during protocolized duration compared with non-protocolized duration (85.52% vs. 48.29%, p < .001). Reintubation rates decreased during protocolized duration (10.9% vs. 4.6%). Hospital stays (20.47 ± 7.06 vs. 27.8 ± 6.2 days, p < .001) and mortality (13.2% vs. 28%, p = .04) were significantly decreased in protocolized duration. Higher age (OR: 2.85, 95% CI 1.22-6.67, p = .02), weight > 10 (OR: 4.37, 95% CI 1.16-16.46, p = .029) and high vasopressor support (OR: 32, 95% CI 6.4-160.13, p < .001) found as significant predictors of non-immediate extubation however only high vasopressor support found to be independent predictor during protocolized duration. CONCLUSIONS: Outcomes in pediatric transplants can be optimized by immediate extubation in majority of cases when protocolized as part of policy.

Living Donor Liver Transplant in patients with Hepatorenal Syndrome without the use of Intraoperative Renal Replacement Therapy, a single-center experience.

BACKGROUND: Continuous Renal Replacement Therapy (CRRT) is often used to support the intraoperative course during liver transplantation (LT) for patients with HRS. However, the use of intraoperative CRRT (IOCRRT) is not without its problems. Living donor liver transplantation (LDLT) is a planned operation and is possible without IOCRRT as the recipient can be optimized. AIM: To study the peritransplant outcomes of patients with CLD and HRS undergoing LT without IOCRRT. METHODS: Analysis of LT program database for perioperative outcomes in patients with HRS from Feb 2017 to Dec 2018. RESULTS: 87/363 (23.9%) adult LDLT patients had HRS, of whom 31 (35.6%) did not respond (NR) to standard medical therapy (SMT) prior to LT. Modified perioperative protocol enabled the NR patients (who were sicker and in persistent renal failure) to undergo LT without IOCRRT. Postoperative renal dysfunction was similar (2 in NR and 2 in R) at 1 year. Post-LT survival was also not different at one month (83.87% in NR and 87.5% in R [p = .640]) and at 1 year (77% in NR vs 80.4% in non-responders [p = .709]). CONCLUSION: IOCRRT can be avoided in HRS patients undergoing LDLT without compromising their outcomes (post-LT survival and RD), even in patients who have not responded to SMT, preoperatively.

Protocol to ensure continued pediatric liver transplantation service during the COVID pandemic and the encouraging outcomes.

Coronavirus disease 2019 is a global pandemic, and to deal with the unexpected, enormous burden on healthcare system, liver transplantation (LT) services have been suspended in many centers. Development of robust and successful protocols in preventing the disease among the recipients, donors and healthcare workers would help in re-starting the LT programs. We adapted a protocol at our center, which is predominantly a living donor liver transplant center based in north India, and continued the service as the pandemic unfolded and peaked in India with good results and shared the experience of the same. Between March 24 and June 7, 2020, during the government-enforced public curfew-"lockdown"-7 children received LT. The protocols of infection control were drafted in our team by local customization of published guidelines. The number of pediatric LT done during the lockdown period in 2020 was similar to that done in corresponding pre-COVID period in 2019. The outcomes were of 100% survival, and none of recipients developed COVID. One potential donor was asymptomatic positive for COVID, responded well to conservative treatment, and was later accepted as a donor. LT program during the COVID pandemic can successfully function after putting in place standard protocols for infection control. These can be implemented with minimal extra involvement of healthcare infrastructure, hence without diversion of resources from COVID management. In conclusion, pediatric liver transplantation services can be continued amid COVID-19 pandemic after establishing a properly observed protocol with minimum additional resources.

Managing Recipient Hepatic Artery Intimal Dissection During Living Donor Liver Transplantation.

Recipient hepatic artery intimal dissection (HAD) followed by hepatic artery thrombosis (HAT) is a serious complication of liver transplantation. Once this is recognized intraoperatively, the accepted approach is to use an alternative arterial inflow, which may not be possible in all patients. We describe a new classification and technique for the management of HAD during living donor liver transplantation. On the basis of the longitudinal extent of intimal dissection, HAD was classified into 4 types. Management was based on the type of dissection, availability of an adequate length of hepatic artery (HA), and an alternate source of inflow. The dissected HA itself was used for arterial anastomosis in patients with preserved pulsatile flow in the dissected artery and a lack of an alternative source of arterial inflow. The technique of using the dissected artery was based on close approximation of the tunica intima to the media with the first 2 sutures of the arterial anastomosis. Of 47 (2.4%) patients who developed HAD, 22 (46.8%) had a type 2 dissection for whom the other (right or the left) undissected HA was used for the anastomosis, and 20 (42.6%) had major (type 3 or 4) dissection. The dissected artery was used for the anastomosis in 9 (45%) of these patients. Postoperative HAT developed in only 1 of 9 patients. Pre-existing portal vein thrombosis and prior transarterial embolization were found to be major risk factors for the development of HAD. Using the technique described, the dissected artery can be successfully used for a satisfactory HA anastomosis with low thrombosis rates.

Minimum absolute graft weight of 650 g predicts a good outcome in living donor liver transplant despite a graft recipient body weight ratio of less than 0.8.

In living donor liver transplant (LDLT), it is recommended to have a minimum graft recipient body weight ratio (GRBWR) 0.8 for good outcomes. Recent reports have, however, shown that good outcomes can be obtained even with GRBWR less than 0.8. We hypothesized that in patients receiving a graft with GRWR less than 0.8 absolute graft weight rather than GRBWR may be more relevant for predicting good outcome. Early post-transplant outcomes were assessed in adult patients undergoing elective right lobe LDLT. Patients were categorized as having good (survival) or poor (mortality) outcome. A ROC curve was drawn based on their graft weights and a cutoff value that provided the highest sensitivity and specificity for a good outcome was chosen. 147 patients received right lobe grafts with GRBWR less than 0.8. The 90-day mortality rate was 13.6% (n = 20). AUROC was 67.7%. Graft weight cutoff of 643 g gave the best combination of sensitivity (51.2%) and specificity (77.8%). There were 15 (19.4%) deaths in group with graft weight less than 643 g compared to 5 (7.1%) patients with graft weight 643 g or above. This cutoff value of 643 g (rounded of to 650 g) gave a positive predictive value (PPV) of 94%.

Living donor liver transplantation in patients weighing ≥100 kg: Low graft weight and obesity do not impact outcomes.

Living donor liver transplantation (LDLT) in obese patients raises concerns with regards to obtaining grafts of "adequate" graft-to-recipient weight ratio (GRWR) and the impact of obesity on the outcomes of LDLT. LDLT outcomes in patients weighing ≥100 kg were compared with those weighing <100 kg. Patients weighing ≥100 kg were divided into 3 categories based on the GRWR of the grafts they received. Groups 1, 2, and 3 included patients with GRWR ≥0.8%, between 0.65% and 0.8%, and <0.65%, respectively. The 56 (6.5%) adult liver transplants were performed in patients weighing 100 kg or more. Except for higher mean body mass index (35.8 versus 25.2 kg/m2 ; P value < 0.01) and grafts of lower GRWR in obese patients (0.74% versus 1.02%; P value < 0.01), all other parameters were similar between the 2 groups. Despite obesity and smaller grafts, the posttransplant outcomes such as day to normal bilirubin and international normalized ratio; infective, respiratory, and biliary complications; and hospital mortality were similar between the 2 groups. On comparing obese patients in the 3 GRWR categories, except for graft weight (985 versus 769 versus 646 g; P value < 0.01), all the pretransplant parameters were comparable. There was no significant difference in terms of graft function, postoperative morbidity, and hospital mortality between patients with grafts of normal GRWR and those with grafts of low and very low GRWR. Grafts of low GRWR give satisfactory results in obese patients undergoing LDLT and obesity does not adversely impact the outcome of LDLT. Liver Transplantation 23:35-42 2017 AASLD.

Vascular complications in living donor liver transplantation at a high-volume center: Evolving protocols and trends observed over 10 years.

Vascular complications continue to have a devastating effect on liver transplantation recipients, even though their nature, incidence, and outcome might have actually changed with increasing experience and proficiency in high-volume centers. The aim of this study was to analyze the trends observed in vascular complications with changing protocols in adult and pediatric living donor liver transplantation over 10 years in 2 time frames in terms of nature, incidence, and outcome. It is a retrospective analysis of 391 (group 1, January 2006 to December 2010) and 741 (group 2, January 2011 to October 2013) patients. With a minimum follow-up of 2 years, incidence of hepatic artery thrombosis (HAT) in adults has reduced significantly from 2.2% in group 1 to 0.5% in group 2 (P = 0.02). In group 2, nonsignificantly, more adult patients (75% with HAT) could be salvaged compared with only 25% patients in group 1 (P = 0.12). However, HAT in children had 100% mortality. Incidence of portal vein thrombosis (PVT) in complicated transplants in 2 eras remained the same (P = 0.2) and so has its mortality. The thrombosis rate of the neo-middle hepatic vein was significantly reduced in group 2 (P = 0.01). The incidence of HAT, particularly in adults, has decreased significantly though PVT has continued to puzzle surgeons in complicated transplants. In high-volume centers, increasing proficiency, technical modifications, early diagnosis, and multimodality of treatment is the key to decrease overall morbidity and mortality due to vascular complications. Liver Transplantation 23 457-464 2017 AASLD.

ABO Incompatible Living Donor Liver Transplantation in Children: A Single Centre Experience from India.

Background: In recent years, paediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report paediatric ABOi LT experience, including short- and long-term outcomes. Methods: It is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n = 20) and non-ABOi (n = 220) paediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. Results: Out of 239 paediatric LDLTs from 2017 to 2022, 19 children (11 females) underwent 20 ABOi LTs (including one retransplant with an ABOi domino allograft) at a median age of 12 (12, 51) months, with the majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day -14 to day -1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture-proven sepsis, and biliary and vascular complications were seen in 10%, 20%, 20%, and 15%, respectively. None of the ABOi LT recipients developed antibody-mediated rejection. ABOi LT recipients, as compared to non-ABOi LT recipients, had a higher incidence of bile leaks and prolonged hospital stay, with the rest of the complications, including biliary strictures and long-term outcomes, being comparable. At a median follow-up of 21 (14, 33) months, 4 children expired (21%). Conclusion: ABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when a compatible liver is unavailable.

Hepatitis A Liver Failure in Children: Native Liver Survival Despite Poor Prognosis.

Background: Hepatitis A virus (HAV) infection is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Literature has shown good outcomes of HAV-induced PALF as compared to other etiologies. The advanced critical care and use of extracorporeal liver assist devices (ELAD) have improved the survival with native liver in PALF and overall outcomes. Various liver transplant listing criteria have been proposed in PALF, however none of them is specific enough to predict the outcome. The timing of liver transplant in living donor setting has never been straightforward. Dynamic clinical and biochemical monitoring of the ALF child is the key to decide for LT. Cases: Here we report three children with HAV-induced PALF presented with advanced hepatic encephalopathy (HE) and high international normalized ratio (INR > 10). These children survived with native liver despite fulfilling the liver transplant criteria. The first child is a 14-year-old male who had peak INR of more than 10.2 and grade 3-4 HE with cerebral edema and acute kidney injury. He responded to medical management and CRRT as liver assist device. The second one is a 7-year-old male child who also recovered well with native liver despite advanced HE and INR of more than 10. Third child is a 16-year-old male who had peak INR of 12.6 and grade 2 HE. He received ELAD (Therapeutic plasma exchange and CRRT) and survived with native liver. Conclusion: Children with HAV-induced PALF can recover with their native liver despite extremely poor prognostic markers like very high INR, ammonia and advanced HE.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Strategies for ABO Incompatible Liver Transplantation.

Liver transplantation (LT) is a definitive treatment for the decompensated liver cirrhosis and fulminant liver failure. With limited availability of cadaveric liver allograft, ABO incompatible (ABOi) living donor liver transplantation (LDLT) plays an important part in further expansion of donor pool. Over the years, with the introduction of Rituximab and improving desensitisation protocol, outcomes of ABOi LDLT are on par with ABO compatible LT. However, ABOi LDLT protocol varies markedly from centre to centre. Intravenous Rituximab followed by plasmapheresis or immunoadsorption effectively reduce ABO isoagglutinins titre before transplant, thereby reducing the risk of antibody mediated rejection in the post-transplant period. Local infusion therapy and splenectomy are not used routinely at most of the centres in Rituximab era. Post-transplant immunosuppression usually consists of standard triple drug regime, and tacrolimus trough levels are targeted at higher level compared to ABO compatible LT. Introduction of newer therapies like Belatacept and Obinutuzumab hold promise to further improve outcomes and reduce the risk of antibody mediated rejection related complications. ABOi LT in emergency situations like acute liver failure and deceased donor LT is challenging due to limited time period for desensitisation protocol before transplant, and available evidence are still limited but encouraging.

Delayed diagnosis of bronchobiliary fistula complicating a pediatric living donor liver transplantation: a case report.

Bronchobiliary fistula (BBF) is a very rare condition in children. Only a few pediatric BBF cases have been reported, in the context of a ruptured hydatid cyst or liver abscess. BBF after living donor liver transplantation (LDLT) has not been reported in the pediatric literature. We report a 7-year-old female child with Wilson disease, who developed BBF post-LDLT. She had a clinically uneventful course in the immediate post-transplant period. She was readmitted on postoperative day (POD) 75 with a productive cough and respiratory difficulty, which was diagnosed as bilioptysis secondary to BBF. Endoscopic retrograde cholangiopancreaticography was attempted but failed. Exploratory laparotomy showed a fistula from the strictured biliary anastomotic site to the right thoracic cavity; it was excised, and a Roux-en-Y hepaticojejunostomy was performed. She tolerated the procedure well and remained clinically well on follow-up through POD 185. BBF is extremely rare in children. This is the first case report of BBF in a child following LDLT. BBF requires a high index of suspicion for a timely intervention to prevent subsequent complications.

Living Donor Liver Transplantation Alone Is Not Inferior to Combined Kidney Liver Transplant for Cirrhotic Patients With Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is common in patients with chronic liver disease (CLD) as is acute kidney injury (AKI). The differentiation between CKD vs AKI is often difficult and sometimes the both may coexist. A combined kidney-liver transplant (CKLT) may result in a kidney transplant in patients whose renal function is likely to recover or at least who have stable renal function post-transplant. We retrospectively enrolled 2742 patients who underwent living donor liver transplant at our center from 2007 to 2019. METHODS: This audit was carried out in liver transplant recipients with CKD 3 to 5 who underwent either liver transplant alone (LTA) or CKLT to look at outcomes and long-term evolution of renal function. Forty-seven patients met the medical eligibility criteria for CKLT. Of the 47 patients, 25 underwent LTA and the rest 22 underwent CKLT. The diagnosis of CKD was made according to the Kidney Disease: Improving Global Outcomes classification. RESULTS: Preoperative renal function parameters were comparable between the 2 groups. However, CKLT patients had significantly lower glomerular filtration rates (P = .007) and higher proteinuria (P = .01). Postoperatively, renal function, and comorbidities were comparable between the 2 groups. Survival was similar at 1, 3, and 12 months, respectively (log-rank; P = .84, = .81, and = .96, respectively). At the end of the study period, 57% of patients who survived in LTA groups had stabilized renal function (Creatinine = 1.8 ± 0.6 mg/dL). CONCLUSIONS: Liver transplant alone is not inferior to CKLT in living donor situations. Renal dysfunction is stabilized in the long term whereas long-term dialysis may be carried out in others. Living donor liver transplantation alone is not inferior to CKLT for cirrhotic patients with CKD.