Risk factors for early and late biliary complications in pediatric liver transplantation

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990–12/2011, medium follow‐up 7.9 yr). One‐, five‐, and 10‐yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26‐fold) and early HAT (<30 days post‐LT; increase 5.87‐fold). Risk factor for primary anastomotic stricture was duct‐to‐duct choledochal anastomosis (increase 5.96‐fold when compared to biliary‐enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09‐fold) and MELD score >30 (increase 1.2‐fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary‐enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.     

Roux‐en‐Y loop varices in children with portal hypertension after liver transplantation: An unusual cause of “obscure” gastrointestinal bleeding

Chu J, Kerkar N, Miloh TA, Rodriguez‐Laiz G, Lewis B, Stangl A, Newton KP, Iyer K, Arnon R. Roux‐en‐Y loop varices in children with portal hypertension after liver transplantation: An unusual cause of “obscure” gastro intestinal bleeding.
Pediatr Transplantation 2011: 15: E156–E161. © 2010 John Wiley & Sons A/S. Abstract: PHALT may result from graft dysfunction, portal vein thrombosis, arterio‐venous fistulas and can lead to GIB, commonly from bleeding esophageal varices. We present three children with GIB requiring multiple blood transfusions that were diagnosed with RY Loop bleeding. Routine EGD, colonoscopy, and CE failed to reveal the bleeding source. However, enteroscopy revealed large varices at the site of hepaticojejunostomy anastomosis in all. Our experience demonstrates that RY loop varices in children with PHALT are a rare and treatable cause of obscure GI bleeding.     

Hepatobiliary scintigraphy for the assessment of biliary strictures after pediatric liver transplantation

Abstract: HBS is used in the management of liver transplantation, a significant complication of which is biliary stricture. Strictures may be intraparenchymal within segments and main duct (non‐anastomotic) or at the biliary‐enteric anastomosis (anastomotic). Strictures are definitively diagnosed, and often managed, by PTC. This is invasive, technically challenging, and requires general anesthesia in young children. HBS may allow early detection of these complications and is non‐invasive. The aim of this study was to review the scintigraphic pattern of biliary strictures using ^99mTcDISIDA HBS following pediatric orthotopic liver transplantation, and to assess its role in the diagnostic algorithm of suspected biliary strictures. All available hepatobiliary studies performed post‐transplant in 101 episodes of liver transplantation in 92 pediatric patients were reviewed. Twenty‐three (23%) patients had known biliary strictures. Twenty‐two patients had adequate studies available for review; five had intrahepatic (non‐anastomotic) strictures alone, nine had a stricture of the anastomosis alone, and eight had both intrahepatic and anastomotic strictures. HBS patterns (either segmental or global changes) correlated very highly with clinically significant biliary strictures. All patients with known strictures had abnormal HBS; hence, in patients with abnormal liver function tests post‐liver transplant, a normal HBS makes strictures very unlikely. We propose that HBS can thus be used to determine if further investigation is required.     

Duct-to-duct biliary reconstruction in pediatric living donor liver transplantation

The results of duct-to-duct biliary reconstruction in six pediatric patients who received a living donor liver transplant aged from 2 months to 11 yr old are reported. The graft was either entire or a part of the left lateral segments. The orifice of the bile duct of the graft was anastomosed to the recipients' hepatic duct in an end-to-end fashion by interrupted suture using 6-0 absorbable material. A transanastomotic external stent tube (4 Fr) was passed through the stump of the recipients' cystic duct. Mean time for reconstruction was 24 min. All the recipients survived the operation and reinitiated oral intake on postoperative day 3. There were no early biliary complications. One 5-yr-old boy suffered from an anastomotic stenosis 9 months after transplantation. He underwent re-anastomosis by Roux-en Y (R-Y) procedure and recovered uneventfully. Duct-to-duct anastomosis in pediatric living donor liver transplantation has benefits while the complication rate is comparable to R-Y reconstruction.     

Roux‐en‐Y enterolith leading to obstruction and ischemic necrosis after pediatric orthotopic liver transplantation

Biliary complications are a common cause of morbidity after liver transplantation, with biliary stone formation being a known occurrence generally upstream of a stricture. A 12‐year‐old boy, who underwent an orthotopic liver transplantation at 11 months of age for biliary atresia, presented acutely with fever and abdominal pain. Cross‐sectional imaging revealed Roux‐en‐Y limb dilatation and thickening. He was explored and was found to have an ischemic Roux limb secondary to an obstructing enterolith. A segmental bowel resection and revision of his hepaticojejunostomy was performed. While rare, biliary enteroliths may present as either a bowel obstruction or cholangitis and should be considered in the differential diagnosis of a patient following biliary reconstruction. Additionally, anatomic etiologies should be considered and potentially surgically corrected.     

Duct-to-duct biliary reconstruction in selected cases in pediatric living-donor left-lobe liver transplantation

Abstract:  The feasibility of D-D biliary reconstruction in pediatric LDLT using left-lobe graft has been discussed in few reports. The use of a trans-anastomotic biliary tube seemed to be the favorable method to avoid the complications according to these reports. We had performed left-lobe LDLT for seven pediatric cases and D-D was done originally. Three cases were converted to R-Y hepaticojejunostomy due to radical resection of hepatoduodenal ligament (n = 1) and severe kinking of D-D (n = 2). Four cases received D-D using 6-0 PDS interrupted sutures without external stent tube. One D-D case died of intra-cerebral hemorrhage 10 days after operation with a functioning graft. There was one biliary leakage in a D-D patient who required PTCD stent for 4 months without any sequale. From our limited experience, D-D biliary reconstruction without external stent tube in left-lobe LDLT is feasible in certain pediatric cases having normal extra-hepatic bile ducts. In smaller recipient with larger graft, the use of a trans-anastomotic biliary tube can prevent anastomotic kinking although we suggest R-Y biliary reconstruction is better for this condition.     

Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes

Anderson CD, Turmelle YP, Darcy M, Shepherd RW, Weymann A, Nadler M, Guelker S, Chapman WC, Lowell JA. Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes.
Pediatr Transplantation 2010: 14:358–363. © 2009 John Wiley & Sons A/S. Abstract: Biliary complications in pediatric LT are important causes of morbidity and graft loss. We examined our recent pediatric LT experience to determine the outcome of post‐LT biliary complications and their relationship to graft type. All initially isolated LTs performed at our institution between January 1, 2000 and August 20, 2007 were reviewed. Recipient data, donor type, graft survival, and biliary complications data were examined. Of 66 LTs, 32 patients received whole organ grafts, and 34 received partial grafts; 11 split, seven reduced size, and 16 live donors. Seventy‐seven percent of patients had biliary reconstruction using a RYH. Overall, 17 (26%) developed biliary complications, and 15 were diagnosed within six months post‐LT. Live donor and split allografts had more biliary complications than reduced size or whole allografts (50% and 36% vs. 0% and 16%, respectively). Seventy‐one percent responded to percutaneous or endoscopic treatment. Five failed initial non‐operative management and required reoperation (one retransplantation). These data suggest that biliary strictures occur most frequently in live donor and split allografts and that non‐operative therapy is highly successful. Partial grafts are essential in pediatric LT, and a high clinical suspicion for biliary complications combined with aggressive and early diagnosis and therapy rarely results in graft loss.     

Outcomes after discontinuation of routine use of transanastomotic biliary stents in pediatric liver transplantation at a single site

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005–2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux‐en‐Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6–8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes.     

New‐onset diabetes mellitus after pediatric liver transplantation

In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high‐risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.     

Feasibility of duct-to-duct biliary reconstruction in pediatric living related liver transplantation: report of three cases

Feasibility of duct-to-duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct-to-duct biliary reconstruction in children, the surgical outcomes of duct-to-duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end-stage liver disease in each of them was fulminant Wilson's disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct-to-duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post-operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow-up of 28 months. In conclusion, our results show that duct-to-duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx.     

Percutaneous removal of biliary stones post‐liver transplant in a pediatric patient: Case report and review of the literature

This case report describes an 8‐year‐old girl who underwent a segmental LT for a primary diagnosis of citrullinemia at the age of 12 months. She presented with cholangitis secondary to stenosis of the biliary‐enteric anastomosis. MRI revealed dilatation of intrahepatic bile ducts associated with multiple stones. An endoscopic approach failed to decompress the bile ducts and remove the stones. A percutaneous approach was then undertaken. After placement of a temporary external biliary drain for 12 days, a 26 French sheath was placed to access the bile ducts. Using a 14Fr flexible cystoscope, 80%‐90% of the biliary stones were removed. This was followed by antegrade balloon dilatation of the biliary‐enteric anastomosis. Two months later, the procedure was repeated, resulting in complete clearance of the biliary stones. An internal‐external biliary drain was maintained in placed for 10 months. The patient has been asymptomatic, with no evidence of stone recurrence for 13 months after drain removal. Percutaneous biliary stone removal is commonly performed in adults with non‐transplanted livers, especially in complex cases, and has also been shown to be successful in the pediatric population. However, it is rarely reported in transplanted livers in adults, and to the best of our knowledge, no pediatric cases have been reported. This case illustrates that this technique can be successfully utilized in pediatric LT patients.     

The impact of thromboelastography on resuscitation in pediatric liver transplantation

Although TEG directs effective resuscitation in adult surgical patients, pediatric data are lacking. We performed a retrospective comparative review of the effect of TEG on blood product utilization and outcomes following pediatric liver transplantation in 38 patients between 2008 and 2014. Diagnoses, laboratory values, fluid and blood product use, and outcomes were examined. Nineteen patients underwent liver transplantation prior to the implementation of TEG, and 19 had perioperative TEG. The most common indications for transplant were BA (n = 14), HB (n = 7), and metabolic disorders (n = 7). Intraoperative blood loss, urine output, fluid and blood product use were similar between groups. However, the use of fresh frozen plasma decreased significantly in TEG patients within the first 24 hours (29 vs 0 mL/kg, P < .01), and between 24 and 48 hours (12 vs 0 mL/kg, P = .01) post‐operatively. The total use of fresh frozen plasma during hospitalization was markedly reduced (111 vs 17 mL/kg, P < .01). Four patients in the TEG group had thromboembolic graft complications, including portal vein or hepatic artery thrombosis, and underwent retransplantation. The decreased use of fresh frozen plasma since implementation of TEG is an important finding for resource utilization and patient safety. However, the increased incidence of thromboembolic complications requires further investigation.     

Hepatitis C viral recurrence in a pediatric patient following liver transplantation

Hepatitis C virus (HCV) infections are known to have a more benign course in children than in adults. Although the natural history of HCV recurrence after liver transplantation has been well studied in adult patients, much less is known about HCV recurrence after liver transplantation in pediatric patients. Herein, we report a case of a pediatric patient with HCV presumably acquired through vertical transmission. She underwent liver transplantation at 14 yr of age. The first three yr after liver transplantation were uneventful. However, in the past 12 months she has been hospitalized twice after developing ascites, hematemesis and esophagogastroduodenoscopy (EGD)-documented esophageal varices. Post-transplant biopsy has demonstrated chronic inflammation complicated with active hepatitis C and stage 2-3 scarring. This case report demonstrates the need for further epidemiologic studies to study the natural history of the rate of HCV recurrence after liver transplantation in the pediatric population.     

Outcome of duct‐to‐duct vs. Roux‐en‐Y hepaticojejunostomy biliary anastomoses in below 15‐kg pediatric liver transplant recipients

The best type of biliary anastomosis to use in lower weight pediatric liver transplant recipients is debatable. In this study, we share a single center's experience comparing the rate of anastomotic biliary complications based on the type of biliary anastomosis performed in this population of patients. A retrospective review of pediatric liver transplants for recipients weighing <15 kg from 11/2003 till 12/2011 was performed. Patients were grouped based on the type of biliary anastomosis into two groups: duct‐to‐duct (d‐d) and Roux‐en‐Y hepaticojejunostomy (h‐j) anastomoses. A total of 24 patients (12 males, 12 females) with a mean age of 26 ± 20 months and a mean weight of 9.27 ± 2.63 kg (range = 5.3–13.9 kg) were studied. All anastomotic complications occurred in patients who received left lateral segments. No statistical differences were found in the post‐operative biliary (p = 0.86) or vascular (p = 0.99) complications between the two groups. Acknowledging the limited sample size, our data suggest that duct‐to‐duct anastomosis can be performed safely in pediatric liver transplantation recipients weighing below 15 kg.     

The kidney in pediatric liver transplantation: An updated perspective

CKD continues to detract from the success of improved survival in pediatric liver transplantation, and its presence is likely under recognized. Here we review the literature regarding the prevalence, etiology, and management of renal dysfunction in pediatric liver transplant recipients. Long‐term studies suggest the prevalence of CKD to be 25–38% by 5–10 yr post‐transplant. While important, sole use of serum creatinine overestimates renal function in this population. Screening for and treatment of persistent proteinuria and hypertension as well as minimization of nephrotoxic insults are the mainstays to delay or prevent CKD progression. Office‐based blood pressure measures are less sensitive than ABPM, which is specifically recommended by the American Heart Association for its ability to diagnose masked hypertension in pediatric liver transplant recipients. Long‐term risk of CKD is predominantly secondary to CNI toxicity. CNI minimization protocols have shown promise in slowing progression of CKD while maintaining graft function, but large‐scale randomized control trials with long‐term follow‐up are needed.     

The technical pitfalls of duct-to-duct biliary reconstruction in pediatric living-donor left-lobe liver transplantation: the impact of stent placement

Abstract:  The feasibility of D-D biliary reconstruction in pediatric LDLT using a left-lobe graft is still controversial. The medical records of 19 pediatric patients (age: four months to 16 yr) were reviewed. The biliary reconstruction was performed in an end-to-end fashion using absorbable sutures. An external biliary tube was placed into the bile duct through the anastomotic site (n = 10) and not through the anastomotic site (n = 4). An external tube was not used in five patients. The median follow-up was 4.7 yr. Nine patients had 11 biliary complications (leakage, n = 2; stricture, n = 7; stricture with leakage, n = 2). Due to biliary complications, conversion to an R-Y was required in five patients, and four patients required radiological or endoscopic management. The patients younger than one yr of age required conversion to R-Y within one wk after LDLT. The analysis of factors related to biliary complications revealed that the use of a trans-anastomotic biliary tube was the only significant factor to avoid biliary complications. In conclusion, D-D biliary reconstruction in LDLT using a left-lobe graft is feasible in selected cases, though it remains challenging. The use of a trans-anastomotic biliary tube is important to avoid biliary complications.     

An institutional experience of pre‐emptive liver transplantation for pediatric primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre‐emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30–46) mL/min/1.73 m² and five underwent sequential combined liver‐kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used “early” or “late.” Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m²), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.