Partial Biliary Diversion May Promote Long-Term Relief of Pruritus and Native Liver Survival in Children with Cholestatic Liver Diseases

Introduction Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. Materials and Methods This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien-Dindo classification system. Results Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3-13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien-Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2-192] vs. 148 [5-383] mu mol/L; p =0.02). Conclusion PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.Peer reviewe

Impaired Neurocognitive Performance in Children After Liver Transplantation

Objectives To assess longitudinal neurocognitive development after liver transplantation and evaluate factors associated with neurocognitive performance. Study design Data from neurocognitive testing of 65 children (aged <18 years) who underwent liver transplantation at Oslo University Hospital between 1995 and 2018 were collected from the testing program after transplantation. The parent-reported version of the Behavior Rating Inventory of Executive Function was used to assess executive function. Results A total of 104 neurocognitive tests were conducted on 65 patients. At the first test, conducted at a median of 4.1 years (IQR, 1.5-5.3 years) after transplantation and at a median age of 6.7 years (IQR, 5.4-10.5 years), the mean full-scale IQ (FSIQ) was 91.7 ± 14, and the mean verbal comprehension index was 92.0 ± 14.5. In the 30 patients tested more than once, there was no significant difference in FSIQ between the first test at a median age of 5.8 years (IQR, 5.2-8.5 years) and the last test at a median age of 10.8 years (IQR, 9.8-12.9 years) (87.4 ± 12.9 vs 88.5 ± 13.2; P = .58). Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age 80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) were associated with FSIQ. Conclusions Young age at transplantation and large blood transfusions during transplantation are risk factors for poor neurocognitive performance later in life. Children who undergo transplantation before 1 year of age have significantly lower neurocognitive performance compared with those who do so later in childhood. Cognitive performance did not improve over time after transplantation

Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation

Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p < 0:001). Univariate associations between GDF-15 and hyperuricemia (p < 0:001), elevated triglycerides (p = 0:028), low HDL (p = 0:038), and obesity (p = 0:028) were found. However, mGFR (p < 0:001) and hemoglobin (p < 0:001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r = −0:343, p = 0:002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function

Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation

Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p < 0:001). Univariate associations between GDF-15 and hyperuricemia (p < 0:001), elevated triglycerides (p = 0:028), low HDL (p = 0:038), and obesity (p = 0:028) were found. However, mGFR (p < 0:001) and hemoglobin (p < 0:001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r = −0:343, p = 0:002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function

Measured GFR by Utilizing Population Pharmacokinetic Methods to Determine Iohexol Clearance

Introduction There is an increasing demand for accurately measured glomerular filtration rate (GFR). Iohexol serum clearance has become a new gold standard, but it is challenging when GFR is low and 24-hour sampling is required for accurate results. The primary aim of this study was to develop an iohexol pharmacokinetic population model for accurate determination of individual GFR using limited sampling for up to 5 hours also when renal function is <40 ml/min. Methods A nonparametric iohexol population pharmacokinetic model was developed with rich data from 176 patients. In a validation cohort of 43 patients, a model-determined GFR (iohexol clearance) using different limited sampling strategies for up to 5 hours was compared with the strategy currently used in routine care, a log-linear 2-point method. In all, 1526 iohexol concentrations were used, from patients ranging in age from 1 to 82 years and GFR from 14 to 149 ml/min. Results The clinical 2-point method showed insufficient agreement compared with reference values; 15% of GFR values had an error of greater than ±10% even when sampling for 24 hours when estimating GFR <40 ml/min per 1.73 m2 (standard procedure). Restricted sampling the first 5 hours with the population model required 4 samples to determine GFR accurately. This strategy showed excellent agreement with the reference; <3% of GFR values had an error greater than ±10 %. Conclusion Using an iohexol population pharmacokinetic model allows for accurate determination of GFR within 5 hours when applying 4 optimally timed samples, even in patients with GFR <40 ml/min

Spectrum of Fontan‑associated liver disease assessed by MRI and US in young adolescents

Abstract Purpose Patients with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. The mechanisms and disease development are unclear and early secondary liver cancer is a concern. This study will describe hepatic imaging findings in a national cohort of adolescents with Fontan circulation. Methods The patients prospectively underwent abdominal contrast enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging. Images were assessed for criteria of fibrosis / cirrhosis including characterization of hepatic nodules. These nodules were in addition, assessed by ultrasonography (US). Nodules ≥ 1 cm were investigated and monitored to evaluate malignant transformation. Clinical and hepatic serological data were recorded. Results Forty-six patients, median age of 16.5 years (15.4–17.9 years) were enrolled. All patients underwent US examination and MRI was performed in 35/46 patients. On MRI, 60% had hepatomegaly and 37% had signs of fibrosis/cirrhosis. Seven patients had together 13 nodules ≥ 1 cm in diameter. Only 4/13 (17%) where seen on US. Nodules had variable MRI signal characteristics including hepatobiliary contrast enhancement and two nodules revealed portal venous phase ‘wash-out’ on the first examination. No further imaging signs of malignancy were revealed during the follow-up period of median 24.4 (7–42) months. Conclusion The majority of adolescents with Fontan circulation had imaging findings of fibrosis/cirrhosis of varying severity. US had low detection rate of hepatic nodules compared to MRI. The imaging work-up before transition to adult cardiology care did not reveal findings suggestive of malignancy. However, the high prevalence of Fontan-associated liver disease calls for surveillance strategies even in childhood

Outcome for biliary atresia patients treated at a low-volume centre

Objectives: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. Methods: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. Results: 45 babies were identified of which 42 (93%) are alive. 41 patients had a Kasai portoenterostomy (PE), two a hepaticojejunostomy and two a primary liver transplantation. The age at PE/hepaticojejunostomy was median 63 (4-145 days). Seven surgeons performed the operations, and the median duration of the diagnostic work-up was 8 (3-24) days. Clearance of jaundice was achieved in 23/43 (53%) babies, and 3- and 5-year native liver survival was 47% and 40% respectively. Clearance of jaundice post PE/hepaticojejunostomy was a strong predictor of native liver survival (adjusted OR: 0.027; 95%; P=0.009). Plasma level of conjugated bilirubin at time of referral was also a significant predictor of native liver survival (adjusted OR: 1.053; P=0.017). Conclusion: A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up, and establishing one dedicated surgical team

Outcome for biliary atresia patients treated at a low-volume centre

Objectives: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. Methods: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. Results: 45 babies were identified of which 42 (93%) are alive. 41 patients had a Kasai portoenterostomy (PE), two a hepaticojejunostomy and two a primary liver transplantation. The age at PE/hepaticojejunostomy was median 63 (4-145 days). Seven surgeons performed the operations, and the median duration of the diagnostic work-up was 8 (3-24) days. Clearance of jaundice was achieved in 23/43 (53%) babies, and 3- and 5-year native liver survival was 47% and 40% respectively. Clearance of jaundice post PE/hepaticojejunostomy was a strong predictor of native liver survival (adjusted OR: 0.027; 95%; P=0.009). Plasma level of conjugated bilirubin at time of referral was also a significant predictor of native liver survival (adjusted OR: 1.053; P=0.017). Conclusion: A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up, and establishing one dedicated surgical team