The Outcome of A Centralization Program in Biliary atresia: 20 years and beyond.

OBJECTIVE: Biliary atresia (BA) is a rare disease and reported outcomes of surgical management, typically a Kasai portoenterostomy (KPE), vary considerably across the world. Centralization has been proposed to improve this. SUMMARY BACKGROUND DATA: A national centralization programme was started in Jan. 1999, involving 3 English units with co-located liver transplant facilities. As the program has now reached the 20-year point, the main aim was to update outcome statistics and identify trends. METHODS: Prospective registry and database. The main measures of outcome were (i) time to KPE, (ii) Clearance of Jaundice (CoJ), defined as reaching a bilirubin value of <20µmol/L (≈1.5 mg/dL), and (iii) actuarial native liver survival (NLS) and overall survival (OS). Data are quoted as median (IQR) and non-parametric statistical comparison used with P<0.05 regarded as significant. RESULTS: 867 infants were born with BA and managed between January 1999 and December 2019. Death occurred without intervention (n=10, 1.1%) or were subject to primary transplant (n=26, 3.0%); leaving 831 (95.9%) infants who underwent KPE at median age of 51 (IQR 39-64) days. Age at KPE reduced over the period (P=0.0001) becoming 48(35-57) days in the last 5-year era. CoJ was achieved in 505/831 (60.6%), also increasing over the period (P=0.002). 42 (5.0%) died post-KPE and 384 were transplanted, leaving 405 alive with their native livers at last follow-up. Of the 412 children transplanted, there were 23 (5.6%) deaths, leaving 387 alive. 5-year and 10-year native liver survival were 51.3% (95% CI 54.8-47.8) and 46.5% (95% CI 50.1 - 42.9) and overall survival were 91.5% (95% CI 93.2 - 89.4) and 90.5% (95% CI 92.3 - 88.2%) respectively. CONCLUSIONS: There have been continued improvements in efficiency over the period of centralization with a significant reduction in time to KPE and improved CoJ following KPE. Overall survival in this disease remains >90%.

Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia.

BACKGROUND AND AIMS: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. APPROACH AND RESULTS: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p <0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p <0.001) also among patients operated <60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004). CONCLUSIONS: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction.

Chest radiographic thoracic areas and respiratory outcomes in infants with anterior abdominal wall defects.

OBJECTIVES: Infants with anterior abdominal wall defects (AWD) can suffer from pulmonary complications. Our aims were to determine if the chest radiographic thoracic areas (CRTAs) on day one differed between infants with exomphalos or gastroschisis, whether this related to differing severity of outcomes and if they were lower than those of controls indicating abnormal antenatal lung growth. METHODS: A review of infants with exomphalos or gastroschisis born between January 2004 and January 2023 was conducted. The control group was term, newborn infants ventilated for poor respiratory drive at birth. Chest radiographs on day one were analysed and the highest CRTA in the first 24 h after birth for each infant included in the analysis. RESULTS: The 127 infants with gastroschisis had a lower gestational age and birthweight than the 62 exomphalos infants and 130 controls (all p<0.001) The CRTAs of the controls were greater than the CRTAs of the exomphalos and the gastroschisis infants (p = 0.001). The median CRTA corrected for birthweight was lower in the exomphalos infants [688, IQR 568-875 mm2/kg] than the gastroschisis infants [813, IQE 695-915 mm2/kg] No gastroschisis infant developed bronchopulmonary dysplasia (BPD). A CRTA of 1759 mm2 had a sensitivity of 81 % and specificity of 71 % in predicting BPD in infants with exomphalos. CONCLUSIONS: Infants with gastroschisis or exomphalos had lower CRTAs than controls suggesting both groups had abnormal antenatal lung development. The CRTA was lower in the exomphalos infants who also had worse respiratory outcomes, hence CRTA assessment may a useful prognostic aid.

Prediction of bronchopulmonary dysplasia by the chest radiographic thoracic area on day one in infants with exomphalos.

OBJECTIVES: To determine if infants with exomphalos had abnormal antenatal lung growth as indicated by lower chest radiographic thoracic areas (CRTA) on day one compared to controls and whether the CRTA could predict the development of bronchopulmonary dysplasia (BPD). METHODS: Infants with exomphalos cared for between January 2004 and January 2023 were included. The controls were term, newborn infants ventilated for absent respiratory drive at birth, without lung disease and had no supplemental oxygen requirement by 6 h of age. The radiographs were imported as digital image files by Sectra PACS software (Sectra AB, Linköping, Sweden). Free-hand tracing of the perimeter of the thoracic area was undertaken and the CRTA calculated by the software. RESULTS: Sixty-four infants with exomphalos and 130 controls were included. Infants with exomphalos had a lower median (IQR) CRTA (1,983 [1,657-2,471] mm2) compared to controls (2,547 [2,153-2,932] mm2, p<0.001). Following multivariable regression analysis, infants with exomphalos had lower CRTAs compared to controls (p=0.001) after adjusting for differences in gestational age and male sex. In the exomphalos group, the CRTAs were lower in those who developed BPD (n=14, 1,530 [1,307-1,941] mm2) compared to those who did not (2,168 [1,865-2,672], p<0.001). Following multivariable regression analysis, the CRTA was associated with BPD development (p=0.021) after adjusting for male sex and gestational age. CONCLUSIONS: Lower CRTAs on day one in the exomphalos infants compared to the controls predicted BPD development.

What Makes A "Successful" Kasai Portoenterostomy "Unsuccessful"?

OBJECTIVES: Clearance of jaundice (CoJ) is the first key objective of Kasai portoenterostomy (KPE) for biliary atresia (BA) and its achievement is by far the best index of long-term prognosis. We sought to identify the reasons for failure [subsequent liver transplant (LT)] in this cohort. METHODS: Review of single-center prospective BA database. Successful KPE was defined by achieving a postoperative bilirubin of ≤20 µmol/L. Pre-KPE and post-KPE variables were identified together with a multivariate logistic regression model to identify those observable at 3 months post-KPE. Data are quoted as median (range). A P value of ≤0.05 was significant. RESULTS: One hundred thirty-five infants underwent KPE between January 2012 and December 2018, of which 90 (67%) achieved CoJ. From these 20 (22%) (Cohort A) underwent LT with the remainder continuing with native liver (Cohort B) (median follow-up of 4.15 years). There was no difference in age at KPE ( P = 0.41), APRi (aspartate aminotransferase-to-platelet ratio) ( P = 0.07), associated anomalies ( P = 0.7), and cytomegalovirus status ( P = 0.7) between the 2 groups. Postoperatively, both cholangitis [any episode, 18/20 (90%) vs 15/70 (21%); P < 0.0001] and portal hypertension (PHT) [gastrointestinal (GI) bleed, 10/20 (50%) vs 2/70 (2.8%); P < 0.0001] were significantly more common in cohort A. Univariate analysis showed that the most significant predictive values at 3 months for LT by 2 years were high APRi, bilirubin, international normalized ratio, and ultrasound (US)-detected ascites with multivariate logistic modeling confirming these variables with predictive values of r2 = 0.79, AUROC = 0.98. CONCLUSIONS: Failure is not preordained at KPE but due to recurrent cholangitis and/or symptoms of PHT.

Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia.

OBJECTIVES: Matrix metallopeptidase-7 (MMP-7) and osteopontin (OPN) are important components in the pathophysiology of fibrosis in biliary atresia (BA). There has been much recent interest in MMP-7 serum level in the diagnosis of BA. We aimed to assess the diagnostic accuracy and prognostic value of both MMP-7 and OPN in a Western BA study. METHODS: Diagnostic value was assessed by comparison of serum MMP-7 and OPN levels in infants with BA and age-matched cholestatic controls. Prognostic value was assessed through subsequent clearance of jaundice (COJ) and need for liver transplantation (LT). RESULTS: Serum was assessed from 32 BA and 27 controls. Median MMP-7 was higher in BA (96.4 vs 35 ng/mL; P < 0.0001) with an optimal cut-off value of 69 ng/mL. Sensitivity and specificity was 68% and 93%, respectively [negative predictive value (NPV) = 71%]. Similarly, median OPN was higher in BA (1952 vs 1457 ng/mL; P = 0.0001) and an optimal cut-off of 1611 ng/mL. Sensitivity and specificity was 84% and 78%, respectively (NPV = 81%). MMP-7 level correlated positively with Ishak liver fibrosis score (r = 0.27, P = 0.04). Neither MMP-7 (70 vs 100 ng/mL; P = 0.2) nor OPN (1969 vs 1939 ng/mL; P = 0.3) were predictive of COJ, or need for LT (99 vs 79 ng/mL; P = 0.7, and 1981 vs 1899 ng/mL; P = 0.2), respectively. CONCLUSIONS: MMP-7 and OPN may have contributory value in the diagnosis of BA, but remain far of the "gold standard" role. Much more prospective data are required and collaborative multi-center initiatives should be the next logical steps.

Reduced Presentation of Biliary Atresia During the COVID-19 Lockdown: A Population Based Observational Study.

OBJECTIVE: The aim of this study was to assess whether there has been a change in presentations of biliary atresia (BA) in England and Wales during the first and second coronavirus disease 2019 (COVID-19) lockdowns (January-June 2020 and 2021). DESIGN: This population study assessed all confirmed cases of BA, from January 2020 to December 2021 across the 3 UK pediatric liver centers originating from England and Wales. Data was then compared to the incidence of confirmed BA cases from January to December 2017, 2018, and 2019. RESULTS: During January-June 2020 and 2021, there were only 8 and 12 presenting cases of BA in England and Wales, compared to 16, 13, and 18 for the same time periods in 2017, 2018, and 2019, respectively. This difference was significant in a two-sided t test for 2020 ( P = 0.035) but not for 2021 ( P = 0.385). There was no difference in the mean days to Kasai procedure in January-June 2020 and 2021 compared to 2017-2019; however average time to Kasai after the lockdown periods was significantly higher. CONCLUSIONS: There was a significant reduction in the presenting cases of BA during the first COVID-19 lockdown, with an increased time for BA referrals after the pandemic lockdowns were lifted in England and Wales.

Historical and Contemporary Management of Infantile Hepatic Hemangioma: A 30-year Single-center Experience.

OBJECTIVE: To describe outcome of infants with hemangioma(s) of the liver. SUMMARY OF BACKGROUND DATA: Infantile hepatic hemangiomas exhibit a diverse phenotype. We report our 30-year experience and describe optimal management based on precise radiological classification. METHODS: Retrospective review of 124 infants (66 female) 1986-2016. Categorical analysis with Chi2 and nonparametric comparison. Data expressed as median (range) and P < 0.05 considered significant. RESULTS: Lesions classified as focal (n = 70, 56%); multifocal (n = 47, 38%) or diffuse (n = 7, 6%) and of these 80(65%) were symptomatic (eg, cardiac failure n = 39, 31%; thrombocytopenia n = 12, 10%).Increased hepatic artery velocity was seen in 63 (56%). Median hepatic artery velocity was greatest in diffuse lesions [245 (175-376) cm/s vs focal 120 (34-242) cm/s vs multifocal 93 (36-313) cm/s; P = 0.0001]. Expectant management alone was followed in 55 (44%). Medical therapy was utilised in 57(46%) and sufficient for symptom control in 29/57 (51%). Propranolol therapy (from 2008) was sufficient for symptom control in 22/28 (79%). Surgery (hepatic artery ligation n = 26; resection n = 13; embolization n = 1) was required in 40 (32%). Median maximal lesion diameter was 3 (0.5-17.1) cm and greater in those requiring surgery (7 cm vs 4.9 cm; P = 0.04). The proportion requiring surgery decreased markedly in the propranolol era [pre-propranolol 25/48 (52%) vs post-propranolol 16/76 (21%) (P = 0.0003)]. Systematic follow-up with ultrasound to a median of 2.6 (0.02-16) years. CONCLUSIONS: A proportion of infantile hepatic hemangiomas remain asymptomatic permitting observation until resolution but the majority require complex multi-modal therapy. First-line pharmacotherapy with propranolol has reduced but not abolished the need for surgery.

Ventilation-to-perfusion relationships and right-to-left shunt during neonatal intensive care in infants with congenital diaphragmatic hernia.

BACKGROUND: We aimed to explore the postnatal evolution of ventilation/perfusion ratio (VA/Q) and right-to-left shunt in infants with congenital diaphragmatic hernia (CDH) and whether these indices predicted survival to discharge. METHODS: Retrospective cohort study at King's College Hospital, London, UK of infants admitted with CDH in 10 years (2011-2021). The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the VA/Q and shunt in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death. RESULTS: Eighty-two infants with CDH (71 left-sided) were included with a median (IQR) gestation of 38.1(34.8-39.0) weeks. Fifty-three (65%) survived to discharge from neonatal care. The median (IQR) VA/Q in the first 24 h was lower in the deceased infants [0.09(0.07-0.12)] compared to the ones who survived [0.28(0.19-0.38), p < 0.001]. In the infants who survived, the VA/Q was lower in the first 24 h [0.28 (0.19-0.38)] compared to pre-operation [0.41 (0.3-0.49), p < 0.001] and lower pre-operation compared to pre-extubation [0.48 (0.39-0.55), p = 0.027]. The shunt was not different in infants who survived compared to the infants who did not. CONCLUSIONS: Ventilation-to-perfusion ratio was lower in infants who died in the neonatal period compared to the ones that survived and improved in surviving infants over the immediate postnatal period. IMPACT: The non-invasive method of the oxyhaemoglobin dissociation curve was used to determine the ventilation/perfusion ratio VA/Q in infants with congenital diaphragmatic hernia (CDH) in the first 24 h of life, pre-operation, pre-extubation and in the deceased infants, before death. The VA/Q in the first 24 h of life was lower in the infants who did not survive to discharge from neonatal care compared to the ones who survived. In the infants who survived, the VA/Q improved over the immediate postnatal period. The non-invasive calculation of VA/Q can provide valuable information relating to survival to discharge.

Quality metrics for emergency abdominal surgery in children: a systematic review.

BACKGROUND: There is variation in care quality and outcomes for children undergoing emergency abdominal surgery, such as appedectomy. Addressing this requires paediatric-specific quality metrics. The aim of this study was to identify perioperative structure and process measures that are associated with improved outcomes for these children. METHODS: We performed a systematic review searching MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar for articles published between January 1, 1980 and September 29, 2020 about the perioperative care of children undergoing emergency abdominal surgery. We also conducted secondary searching of references and citations, and we included international professional publications. RESULTS: We identified and analysed 383 peer-reviewed articles and 18 grey literature publications. High-grade evidence pertaining to the perioperative care of this patient group is limited. Most of the evidence available relates to improving diagnostic accuracy using preoperative blood testing, imaging, and clinical decision tools. Processes associated with clinical outcomes include time lapse between time of presentation or initial assessment and surgery, and the use of particular analgesia and antibiotic protocols. Structural factors identified include hospital and surgeon caseload and the use of perioperative care pathways. CONCLUSIONS: This review summarises the structural and process measures associated with outcome in paediatric emergency abdominal surgery. Such measures provide a means of evaluating care and identifying areas of practice that require quality improvement, especially in children with appendicitis. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42017055285.

Prediction of survival in infants with congenital diaphragmatic hernia and the response to inhaled nitric oxide.

The use of inhaled nitric oxide (iNO) in treating pulmonary hypertension in infants with congenital diaphragmatic hernia (CDH) is controversial. Our aims were to identify factors associated with survival in CDH infants and whether this was influenced by the response to iNO. Results of CDH infants treated in a tertiary surgical and medical perinatal centre in a ten year period (2011-2021) were reviewed. Factors affecting survival were determined. To assess the response to iNO, blood gases prior to and 30 to 60 min after initiation of iNO were analysed and PaO2/FiO2 ratios and oxygenation indices (OI) calculated. One hundred and five infants were admitted with CDH; 46 (43.8%) infants died. The CDH infants who died had a lower median observed to expected lung to head ratio (O/E LHR) (p < 0.001) and a higher median highest OI on day 1 (HOId1) (p < 0.001). HOId1 predicted survival after adjusting for gestational age, Apgar score at 5 min and O/E LHR (odds ratio 0.948 (95% confidence intervals 0.913-0.983)). Seventy-two infants (68.6%) received iNO; 28 survived to discharge. The median PaO2 (46.7 versus 58.8 mmHg, p < 0.001) and the median PaO2/FiO2 ratio (49.4 versus 58.8, p = 0.003) improved post iNO initiation. The percentage change in the PaO2/FiO2 ratio post iNO initiation was higher in infants who survived (69.4%) compared to infants who died (10.2%), p = 0.018. CONCLUSION: The highest OI on day 1 predicted survival. iNO improved oxygenation in certain CDH infants and a positive response was more likely in those who survived. WHAT IS KNOWN: • The use of iNO is controversial in infants with CDH with respect to whether it improves survival. WHAT IS NEW: • We have examined predictors of survival in CDH infants including the response to iNO and demonstrated that the highest oxygenation index on day 1 predicted survival (AUCROC =0.908). • Certain infants with CDH responded to iNO and those with a greater response were more likely to survive.

Adult Liver Disease Prognostic Modelling for Long-term Outcomes in Biliary Atresia: An Observational Cohort Study.

OBJECTIVES: To assess the utility of prognostic scoring systems for adolescents with biliary atresia (BA) surviving with native liver, for predicting the subsequent requirement for liver transplantation (LT). METHODS: Single-centre retrospective analysis of 397 BA patients who received Kasai Portoenterostomy (KP) 1980-1996 and survived with the native liver at 16 years. Laboratory and clinical variables at 16 years (timepoint 16 years) were used to calculate (i) LT allocation scores; Model for End-Stage Liver Disease [MELD/MELD-sodium (Na)], and UK End-Stage Liver Disease (UKELD); (ii) Mayo Primary Sclerosing Cholangitis risk score (MayoPSC) and (iii) a modified Paediatric End-Stage Liver Disease (PELD) score. Scores were compared between patients requiring LT after 16 years of age (LT > 16 years), and those who survived with native liver, at the latest follow-up. Additional subgroup analysis for patients with data available at 12 years (timepoint 12 years). RESULTS: MELD (area under the receiver operating characteristic [AUROC] 0.847) and UKELD (AUROC: 0.815) at 16 years of age predict the need for LT > 16 years. No advantage for MELD-Na over MELD was demonstrated. MELD >8.5 and UKELD >47 predicted LT > 16 years with 84% and 79% sensitivity and 73% and 73% specificity. PELD had a similar performance to MELD, but superiority to UKELD. MayoPSC revealed predictive accuracy for LT >16 years (AUROC 0.859), with a score of >0.87 predicting LT > 16 years with 85% sensitivity and 82% specificity. At timepoint 12 years, MELD and MayoPSC predicted LT >16 years. Change in MELD, PELD and MayoPSC between 12 and 16 years of age, was associated with LT >16 years. CONCLUSIONS: Adult LT allocation scores may help monitor progress in adolescent BA, but the omission of relevant risk factors limits their utility for listing in this cohort. A BA-specific prognostic score would improve the management of adolescent BA.

Developmental histology of the portal plate in biliary atresia: observations and implications.

PURPOSE: The key characteristic of biliary atresia (BA) is obliteration of the extrahepatic bile ducts at the level of the porta hepatis. We aimed to relate the immunohistochemical features of remnant biliary ductules at the porta hepatis with clinical features and outcomes. METHODS: Samples were immunostained with anti-cytokeratin 20 (CK20), vimentin and alpha-smooth muscle actin (aSMA). Primary outcome was set as clearance of jaundice (bilirubin ≤ 20 µmol/L) following Kasai portoenterostomy (KPE). RESULTS: Eighty-two cases were classified into syndromic BA (n = 10), cystic BA (n = 7), CMV IgM+ BA (n = 9) and isolated BA (n = 56). CK20 expression was confirmed in 40/82 (49%), and vimentin expression in 19/82 (23%). aSMA was negative in all cases studied. CK20 expression was less common in isolated BA (n = 20/56, 36%) compared to CMV IgM+ BA (n = 8/9, 89%), cystic BA (n = 7/7, 100%) (isolated BA vs non-isolated BA, P = 0.0008). There was no difference in vimentin expression among the sub-groups (isolated BA vs. non-isolated BA; P = 0.39). CoJ was achieved in 52/82 (63%) overall with significant difference depending simply on sub-group [e.g. syndromic BA 9/10 (90%)]. CK20 expression was associated with a diminished rate of CoJ in the entire cohort [CK20+ 32/56 (57%) vs. CK20- 20/26 (77%); P = 0.04]. By contrast no correlation was observed between vimentin expression and CoJ (P = 0.13). CONCLUSION: CK20+ expression was associated with reduced clearance of jaundice in BA and a trend towards reduced native liver survival.

Endoscopic Retrograde Cholangiopancreatography in Infants: Availability Under Threat: A Survey on Availability, Need, and Clinical Practice in Europe and Israel.

Endoscopic retrograde cholangiopancreatography (ERCP) in infants (younger than 1 year of age) is a highly specialized procedure. Since 2014 opportunities to maintain or purchase duodenoscopes for ERCP in infants have disappeared. In a survey among European hepatology centers (including Israel) we evaluated the availability, need, indications, and practice of ERCP procedures in infants. It shows that infant ERCP is a low-volume procedure (median 5 procedures/year) in the 14 centers that perform this procedure. Since 2014 several centers no longer have an infant ERCP duodenoscope due to breakdown. In addition, substantial differences exist between centers in indications, types of interventions performed, and practical execution of ERCP procedures in infants. We conclude that a concerted effort by the pediatric hepatology community is needed to secure the future availability of infant ERCP. In addition, consensus on the indications and optimal use of infant ERCP could improve the quality of ERCP care for infants.

Antenatal corticosteroids and outcomes in gastroschisis: A multicenter retrospective cohort study.

OBJECTIVE: In gastroschisis, there is evidence to suggest that gut dysfunction develops secondary to bowel inflammation; we aimed to evaluate the effect of maternal antenatal corticosteroids administered for obstetric reasons on time to full enteral feeds in a multicenter cohort study of gastroschisis infants. METHODS: A three center, retrospective cohort study (1992-2013) with linked fetal/neonatal gastroschisis data was conducted. The primary outcome measure was time to full enteral feeds (a surrogate measure for bowel function) and secondary outcome measure was length of hospital stay. Analysis included Mann-Whitney and Cox regression. RESULTS: Of 500 patients included in the study, 69 (GA at birth 34 [25-38] weeks) received antenatal corticosteroids and 431 (GA at birth 37 [31-41] weeks) did not. Antenatal corticosteroids had no effect on the rate of reaching full feeds (Hazard ratio HR 1.0 [95% CI: 0.8-1.4]). However, complex gastroschisis (HR 0.3 [95% CI: 0.2-0.4]) was associated with an increased time to reach full feeds and later GA at birth (HR 1.1 per week increase in GA [95% CI: 1.1-1.2]) was associated with a decreased time to reach full feeds. CONCLUSION: Maternal antenatal corticosteroids use, under current antenatal steroid protocols, in gastroschisis is not associated with an improvement in neonatal outcomes such as time to full enteral feeds or length of hospital stay.

Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood.

BACKGROUND & AIMS: In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age. METHODS: This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980-96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6-17.4 years). RESULTS: The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively. CONCLUSIONS: BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value. LAY SUMMARY: Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.

Acute-on-chronic liver failure in children with biliary atresia awaiting liver transplantation.

OBJECTIVES: Acute-on-chronic liver failure (ACLF) is an acute decompensation of cirrhosis complicated by other organ failure and is associated with increased mortality and morbidity. ACLF has not been studied in children with biliary atresia (BA), which is the commonest indication for pediatric liver transplantation (LT) worldwide. This study aims to evaluate ACLF and outcomes in children with BA while awaiting deceased donor LT. METHODS: This was a subanalysis of the dataset from a prospective cohort study of patients aged 0-18 years who underwent portoenterostomy for BA and were listed for LT at King's College Hospital, London, between 1999 and 2003. Outcomes included the development of ACLF, mortality, and complications. RESULTS: Ninety-nine (41 male) children were included, and follow-up was 10 [6.0-15.0] years. A total of 20/99 children developed ACLF. ACLF was associated with increased mortality while awaiting LT (20% vs 4%; P = 0.03). There were no associations between biochemical parameters at listing and death. Increased bilirubin levels 3 months post-portoenterostomy was predictive of development of ACLF (AUROC = 0.72, P < 0.01). Age at LT and time on the waiting list in the ACLF subgroup were both lower compared to the non-ACLF group (P > 0.05). Sepsis and gastrointestinal bleeding were the commonest precipitants of ACLF. Complications included ascites, hepatic encephalopathy, and hepatorenal syndrome; the ACLF subgroup required multisystem support and longer intensive care unit stay. CONCLUSIONS: ACLF in children with BA awaiting deceased donor LT carries increased mortality and morbidity. This warrants stratification of patients for earlier wait-listing and prioritization for LT.

Choledochal malformations: global research, scientific advances and key controversies.

Choledochal malformations (CMs) represent a spectrum of relatively rare and complex congenital anomalies, characterized by abnormal dilatation of the biliary tract in the absence of any acute obstruction. Today, almost 20% of CMs can be detected in-utero using maternal ultrasonography. Formal scientometric analysis was used to identify where modern CM research is taking place and perhaps where our attention should be directed in the future. Thus, this article offers a comprehensive review of recent scientific advances relating to CMs including the current understanding of etiology and classification, whilst also discussing key controversies such as risk of malignant transformation and the role of newer modalities of surgical treatment. Although laparoscopic excision of CMs and biliary reconstruction is nowadays feasible and safe, care should be taken before dispensing with standard open techniques, which have minimal complication rates and proven long-term benefit.

Correction to: Choledochal malformations: global research, scientific advances and key controversies.

The last sentence in the first paragraph under subheading "Minimally invasive treatment" was incorrect in the original publication.