Biological abdominal wall expansion in pediatric liver recipients after transplantation with large‐for‐size organs

Background After pediatric split liver transplantation, intra-abdominal loss of domain due to large-for-size left lateral grafts is a frequent problem for fascial closure and potentially leads to reduced liver perfusion and abdominal compartment syndrome. Therefore, delayed fascial closure with the use of temporary silastic meshes and reoperation or alternative fascial bridging procedures are necessary. Methods Between March 2019 and October 2021, biologic meshes were used for abdominal wall expansion in 6 cases of pediatric split liver transplantation. These cases were analyzed retrospectively. Results One male and 5 female children with median age of 6 months (range: 0–57 months) and weight of 6 kg (range: 3.5–22 kg) received a large-for-size left lateral graft. Graft-to-recipient weight ratio (GRWR) was 4.8% (range: 1.5%–8.5%) in median. Biologic mesh implantation for abdominal wall expansion was done in median 7 days (range: 3–11 days) after transplantation when signs of abdominal compartment syndrome with portal vein thrombosis in 3 and of the liver artery in 1 case occurred. In 2 cases, bovine acellular collagen matrix and 4 cases ovine reinforced tissue matrix was used. Median follow-up was 12.5 months (range: 4–28 months) and showed good liver perfusion by sonography and normal corporal development without signs of ventral hernia. One patient died because of fulminant graft rejection and emergency re-transplantation 11 months after the initial transplantation. Conclusions Biologic meshes can be used as safe method for abdominal wall expansion to achieve fascial closure in large-for-size liver transplant recipients. Usage for primary fascial closure can be considered in selected patients

Successful auxiliary two-staged partial resection liver transplantation (ASPIRE-LTx) for end-stage liver disease to avoid small-for-size situations

Background Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. Case presentation Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. Conclusions Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety

Good outcomes after repeated pediatric liver retransplantations: A justified procedure even in times of organ shortage

Background Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic. Methods Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra- and postoperative course and overall survival (OS) were analyzed. Results Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1–192 months), 60.5 (range: 1–215 months), 58.5 (range: 14–131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs. Conclusion Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential

Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AIMS Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, main causes are viral infections (12-16%) and inherited metabolic diseases (14-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. METHODS With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF (RALF). WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (46%), and in children with RALF (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8) and DGUOK (n=7) were the most frequent findings. When categorizing, most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%) and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplants. CONCLUSION This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Genetic landscape of pediatric acute liver failure of indeterminate origin

BACKGROUND AND AIMS: Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. APPROACH AND RESULTS: With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS: In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (41%), and in children with recurrent acute liver failure (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8), and DGUOK (n=7) were the most frequent findings. When categorizing, the most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%), and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplantation. CONCLUSIONS: This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Risk factors associated with cognitive impairment in patients after pediatric liver transplantation

Data on cognitive function after pLT are rare, particularly regarding children with cognitive impairment. From 2016 to 2018, we evaluated cognitive function in 36 patients after pLT aged 6‐17 years with the WISC IV (at least 1 year after transplantation) and analyzed potential risk factors for cognitive impairment (IQ < 70) by means of retrospective medical data (peri‐, intra‐, and post‐operative factors, and donor and specific organ data of the primary liver transplant) on an exploratory base. At a median age of 9.6 years (range = 6‐16.9), 22% of patients were cognitive impaired (IQ < 70; including five untestable patients with severe cognitive impairment). Children tested with the WISC IV scored within the lower normal range but differed significantly from normal population. Strongest associations showed infections at pLT, development of severe sepsis requiring intensive care within the first 6 months after pLT, neurological complications within the first 10 days and the occurrence of CPR during or after pLT, and as early laboratory variables pH value on day 0 after pLT. In our analysis, neither intraoperative factors nor donor‐specific factors seemed to influence cognitive outcome. In our small cohort, medical complications before and after pLT but not transplantation itself had an influence on cognitive outcome. As such, children experiencing medical problems before and in the early post‐operative phase after pLT should be closely evaluated in larger samples regarding their neurological and psychomotor development during vulnerable phases and should receive early educational support to improve long‐term cognitive function

Sequential CT arterioportography-arteriosplenography depicts individual haemodynamic changes in children with portal hypertension without cirrhosis

We evaluated sequential computed tomography (CT) arterioportography-arteriosplenography for the assessment of venous pathways in children with portal hypertension without cirrhosis. Institutional Review Board approval was obtained for this retrospective, single-centre study. CT was performed after contrast application via catheters placed in the superior mesenteric artery (CT arterioportography) and the splenic artery (CT arteriosplenography) consecutively. Venous pathways in 22 children were evaluated. In all patients, the detailed haemodynamic consequences of portal hypertension could be characterised. The supply of varices at different locations could be assigned to the superior mesenteric vein or splenic vein system. Retrograde blood flow through the splenic vein and inferior mesenteric vein, portosystemic shunting, and patency of splanchnic veins were determined. CT arterioportography-arteriosplenography allowed a complete evaluation of individual haemodynamic pathways in children with portal hypertension

Acute Kidney Injury and Renal Regional Oxygen Saturation During Pediatric Liver Transplantation

Background: Kidney injury is a complication among children undergoing liver transplantation (pLTx). Cystatin C serum con- centration seems to be superior to creatinine-based determination of kidney injury in adults and children. Nearinfrared spectroscopy (NIRS) technology provides non-invasive and real-time measurement of renal tissue oxygenation. Here, we compared renal tissue oximetry (rSrO(2)) with conventional diagnostic criteria cystatin C and creatinine concentration in children undergoing pLTx. Material/Methods: rSrO(2) was measured intraoperatively in children undergoing pLTx over the left kidney, and was statistically com- pared with pre- and postoperative serum creatinine and cystatin C concentrations. Results: rSrO(2) was affected by hemoglobin concentration, bilirubin concentration, and FiO(2). Statistical analysis dem- onstrated that rSrO(2) was significantly reduced in children with preoperative pathologic increased cystatin C concentrations compared to children without (63.7 +/- 4.3 vs. 53.4 +/- 4.9, p<0.05). We did not detect a significant difference in rSrO(2) between children who developed postoperative renal impairment, either determined by increased postoperative cystatin C concentration, creatinine concentration, or the pRIFLE criteria. lntraoperative increase or decrease in rSrO(2) did not predict the development of postoperative kidney injury. Conclusions: In children with liver failure undergoing pLTx, a preoperative decrease in rSrO(2) indicates compromised renal function. However, intraoperative rSrO(2) is not predictive of postoperative kidney injury