Post-Kasai portoenterostomy (KPE) cholangitis is one of the most common complications that has a negative impact on liver function and native liver survival. Early diagnosis and judicious empiric antimicrobial management are, therefore, important to prevent further liver damage and decompensation. However, there is no consensus regarding the standard definition of post-KPE cholangitis, and established guidelines on evaluation and management are also lacking. Metagenomic next-generation sequencing, a new molecular diagnostic technique, has the potential for detecting broader spectrum of pathogens, especially in blood culture-negative patients. Antibiotic prophylaxis to prevent cholangitis has been widely used, but questions over the choice of antibiotics, route of administration, and optimal duration remain unsettled. The available evidence on the efficacy of antibiotic prophylaxis in preventing cholangitis has shown conflicting results. This review offers a summary of the current research on advances in diagnostic approaches, including molecular techniques, and therapeutic challenges in managing intractable cholangitis.

Pediatric surgeons often obtain intraoperative liver wedge biopsies during Kasai portoenterostomy for biliary atresia despite an existing preoperative core needle biopsy. We conducted a single-institution retrospective review analyzing preoperative factors, Batts-Ludwig fibrosis stage (preoperative percutaneous core needle and intraoperative wedge biopsies), and survival with native liver from 2004 to 2023. Of 116 patients, 87 underwent both preoperative and intraoperative biopsies, with discordant results observed in 30/87 (34.5 ​%) patients. Of the discordant samples, intraoperative wedge biopsies upstaged the Batts-Ludwig scoring system in 97 ​% of biopsies. Neither the core needle (p ​= ​0.80) nor wedge (p ​= ​0.18) fibrosis stage correlated with native liver survival at one year. Age at surgery (58 vs. 63 days, p ​= ​0.04), aspartate transferase (145 vs. 195 U/L, p ​= ​0.05), and alanine transferase (108 vs. 143 U/L, p ​= ​0.03) demonstrated associations with native liver survival at one year. Our data suggests that routine intraoperative wedge biopsies may not be necessary after preoperative core biopsies.

Biliary atresia (BA) is the most common cause of end-stage liver disease in children. Around 5 %-15 % of patients with BA have a congenital heart disease (CHD) diagnosis. Despite high prevalence of a CHD diagnosis in patients with BA, outcomes of Kasai portoenterostomy (KPE) in the CHD population remain unexplored.

This is a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database from 2012 to 2022. All patients undergoing KPE were included. Patients with CHD were identified using previously validated ICD9/10 codes.

A total of 854 patients underwent a KPE during the study period. Of this cohort, 502 (59 %) were female, 342 (40 %) White Non-Hispanic, median age of 57.0[IQR: 40.0-72.0] days, and a median weight of 9.4 [IQR: 8.1-10.7] kilograms. A total of 89 (10 %) patients had a diagnosis of CHD. Of those, 63 (7 %) had a simple-CHD diagnosis and 26 (3 %) a complex-CHD diagnosis. A single-ventricle (SV-CHD) diagnosis was present in 7 (1 %) patients. Notably, no in-hospital mortalities were found. When compared to non-CHD, simple-CHD (OR: 2.51; 95 % CI: 1.45-4.36, p = 0.001) and complex-CHD (OR: 3.20; 95 % CI: 1.30-7.87, p = 0.011) had increased risk for any complication. Furthermore, when compared to non-CHD complex-CHD patients had higher odds of undergoing a Kasai related reintervention (OR: 5.01; 95 % CI: 1.76-14.22, p = 0.002. After propensity score matching, when compared to non-CHD a CHD diagnosis was only associated with an increased risk for any complication (OR: 2.50; 95 % CI: 1.30-4.81, p = 0.005).

A CHD diagnosis is present in 10 % of children undergoing KPE. KPE appears to be safe in patients with CHD, but associated with increased in-hospital resource utilization. Further studies are needed to understand the impact of a CHD diagnosis on the long-term outcomes after KPE.

Retrospective Review.

Level 3.

To develop a machine learning algorithm with prognosis data to identify different clinical phenotypes of biliary atresia (BA) and provide instructions for choosing treatment schemes.

Six hundred thirty-nine cases of type III BA were retrospectively collected from the Children's Hospital of Fudan University from Jan 1st, 2017 to Dec 1st, 2019 as a training dataset, and a survival-based forward clustering method, which can also be used to predict the subtype of a new patient was developed to identify BA subtypes.

A total of 2 clusters were identified (cluster 1 = 324 and cluster 2 = 315), where cluster 2 had a lower 2 y native liver survival post-Kasai rate. The infant patients in cluster 2 have higher weight, liver, and spleen volume, wider portal vein width, and older operative age; worse coagulation and liver function results; higher grade of liver fibrosis and detection rate of hepatic portal fibrous mass, and higher recent infection detection rate of herpes simplex virus type I. With the proposed prognostic classification system, the authors predicted the subtypes of the 187 cases of type III BA in a testing dataset collected from the whole year of 2020. The p-value computed from the log-rank testing for the Kaplan-Meier survival curves of the predicted two testing groups was 0.0113.

This classification system would be a convenient tool to choose appropriate treatment and accelerate the choice-making between clinicians and infant patients.

Biliary atresia (BA) is a progressive disease affecting the bile duct structure and function, leading to poor outcomes without timely surgical intervention. Kasai portoenterostomy (KPE) is a commonly used treatment to restore bile flow. However, the success rate and postoperative outcomes of KPE vary with different surgical techniques, including laparoscopic, robot-assisted, and open approaches.

Following the PRISMA guidelines, this study systematically searched PubMed, EMBASE, and Cochrane databases for literature on BA surgical techniques of KPE. Studies comparing two or all three techniques-laparoscopic, robot-assisted, and open-in terms of postoperative outcomes of KPE in BA patients were included. Utilizing the "gemtc" package in R version 4.3.3, NMA was conducted to compare postoperative clearance of jaundice (COJ) among different surgical techniques. We also performed traditional paired meta-analysis in which multiple surgical outcomes were compared.

According to the traditional definition of a successful KPE surgery, in terms of successful postoperative COJ, robotic-assisted Kasai portoenterostomy (RAKPE) shows advantage over open Kasai portoenterostomy (OKPE) and laparoscopic Kasai portoenterostomy (LKPE), while the outcomes between OKPE and LKPE are equivalent. However, statistically speaking, there is no significant difference among the three techniques. LKPE has a longer operation time and less intraoperative bleeding compared to OKPE. There are no statistically significant differences in hospital stay, cholangitis incidence, or liver survival rates at 6 months, 1 year, 2 years, or 5 years.

The surgical success rates of KPE with various technical aids are similar, highlighting the need to consider individual patient conditions and cost when choosing a surgical technique. Effective postoperative management is vital for preventing complications and slowing liver fibrosis. Future research should focus on improving surgical techniques and postoperative care to enhance long-term outcomes for BA patients. For those who cannot maintain liver function with KPE, timely LT consideration is crucial.

This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE).

This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve.

Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75).

In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up.

Level III.

In recent decades, the survival of children with congenital anomalies and paediatric cancer has improved dramatically such that there has been a steady shift towards understanding their lifelong health outcomes. Paediatric surgeons will actively manage such conditions in childhood and adolescence, however, adult surgeons must later care for these 'grown-ups' in adulthood. This article aims to highlight some of those rare disorders encountered by paediatric surgeons requiring long-term follow-up, their management in childhood and their survivorship impact, in order that the adult specialist may be better equipped with skills and knowledge to manage these patients into adulthood.

A comprehensive literature review was performed to identify relevant publications. Research studies, review articles and guidelines were sought, focusing on the paediatric management and long-term outcomes of surgical conditions of childhood. The article has been written for adult surgeon readership.

This article describes the aforementioned conditions, their management in childhood and their lifelong implications, including: oesophageal atresia, tracheo-oesophageal fistula, malrotation, short bowel syndrome, duodenal atresia, gastroschisis, exomphalos, choledochal malformations, biliary atresia, Hirschsprung disease, anorectal malformations, congenital diaphragmatic hernia, congenital lung lesions and paediatric cancer.

The increasing survivorship of children affected by surgical conditions will translate into a growing population of adults with lifelong conditions and specialist healthcare needs. The importance of transition from childhood to adulthood is becoming realized. It is hoped that this timely review will enthuse the readership to offer care for such vulnerable patients, and to collaborate with paediatric surgeons in providing successful and seamless transitional care.

Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.

To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA.

This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test.

Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival.

In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.

This study analyzed the results of a transition program in a patient population with a rare liver disease of pediatric onset.

Data were collected on the clinical course of an adolescent population with a rare disease of pediatric onset and enrolled in a transition program between 1994 and 2022.

A total of 238 adolescents (including 34 having undergone a liver transplant on enrolling in the program) were included. Eight patients were lost to follow-up before the first transition consultation and 16 families requested follow-up in an adult hepatology department closer to their home. Overall, 214 initial transition consultations were carried out; 29 patients were subsequently lost to follow-up and 13 switched center. Overall, 15.4 % of the patients enrolled in our program were lost to follow-up. Five adult patients underwent a liver transplantation during this 28-year period. Overall mortality was 3.2 %, graft survival was 91.5 %, and posttransplant survival was 92 %. In total, the current active file represents 183 patients with a median age of 24.3 years (18-51) and a median follow-up period of 5.8 years (6 months to 28 years).

The implementation of a transition program to adult medicine for adolescents with a rare liver disease should follow the recommendations but must be adapted in line with local practice conditions. This process requires close collaboration between the pediatric and adult medicine teams based on a mutual desire to constantly improve practices and enhance knowledge.

Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis.

There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute.

There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001).

The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients.

What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

Biliary atresia (BA) is rare liver disease of unknown etiology, and is a major indication for liver transplant (LT). Previous data indicate improved outcomes with early referral for Kasai portoenterostomy (KPE).

Evaluate the long-term outcomes in BA, with particular focus on those transitioned to adult care with native livers.

Patients with BA treated between1980 and 2012 were identified. Data were collected from the time of referral, transition to adult care, and the most recent clinic notes, from which patient and native liver survival were calculated.

Four hundred and fifty-four patients with BA were identified, who were followed up for median of 16.4 years from birth; 74 died (41 of whom had a LT), giving a 20-year survival rate of 83.6%. Two hundred and seventy-two patients received an LT, with the median native liver survival being 35 months. Of patients who transitioned to adult care, 54 of 180 (30.0%) retained their native liver. Of these, 72% (39 of 54) had evidence of chronic liver disease at transition, of whom 8 were subsequently lost to follow-up, 9 were transplanted, and 22 remained stable with compensated liver disease. Of the 15 of 54 patients (28%) with no evidence of chronic disease in their native liver disease at transition, 3 were subsequently lost to follow-up; none received transplants, although 3 patients developed new-onset liver disease. All patients transitioned to adult care completed secondary school education (N = 180), with 49% having attended college/university and 87% being in employment or education at the last follow-up. Of female patients, 34% had at least one pregnancy (27 children in 21 women), while 22% of males had fathered a child.

Long-term outcomes in BA are good, with patients surviving into adult life. Progression of chronic liver disease and associated morbidity is common in those who retained their native livers, suggesting that these patients require monitoring of liver disease throughout adult life, and early recognition of the need for LT.

Timing for liver transplantation (LT) in biliary atresia (BA) children with end-stage liver disease (ESLD) is associated with all-cause mortality. The cut-off value of pediatric end-stage liver disease (PELD) score for LT consideration varies across institutions. We aimed to determine the cost-effectiveness of LT to prevent death among BA children registered on the waiting list with different severities of ESLD.

Subjects were BA children aged < 12 years at a transplant center between 2010 and 2021. A decision tree was developed for cost-effectiveness analysis from a hospital perspective to compare all-cause death between patients initially registered with a low PELD score (< 15) and a high PELD score (≥ 15). Each patient's direct medical cost was retrieved from the beginning of registration until 5 years after LT, adjusted with an inflation rate to 2022 Thai Baht (THB).

Among 176 children, 138 (78.4%) were initially registered with the high PELD score. The cost and mortality rate of the low PELD score group (THB1,413,424 or USD41,904 per patient and 31.6% mortality) were less than the high PELD score group (THB1,781,180 or USD52,807 per patient and 47.9% mortality), demonstrating the incremental cost-effectiveness ratio (ICER) of THB2,259,717 or USD66,994 per death prevented. The cost of early post-operative admission had the highest effect on the ICER. Considering the break-even analysis, cost among children initially registered at the low PELD score was also less expensive over time.

Registration for LT at PELD score < 15 was more cost-effective to prevent death among BA children with ESLD.

To evaluate the response and outcome with prolonged intravenous antibiotics including home-based intravenous antibiotics in children with intractable cholangitis (IC) after Kasai portoenterostomy (KPE) for biliary atresia (BA).

A retrospective review of treatment and outcome of children with IC post KPE (no resolution after four weeks of antibiotics) was done between 2014 and 2020. A protocol-based antibiotic regimen was used based on sensitivity and hospital antibiogram. Children afebrile for more than three days were discharged on home intravenous antibiotics (HIVA).

Twenty children with IC were managed with prolonged antibiotic regimen, including HIVA. All patients were initially listed for liver transplantation (LT) with indication being IC (n = 20) with portal hypertension (n = 12). Seven patients had bile lakes of which four underwent percutaneous transhepatic biliary drainage. Bile culture grew Klebsiella in four and Escherichia coli and Pseudomonas one each. There were eight children with IC who had positive blood culture with most of these organisms being gram-negative (Escherichia coli: 5, Klebsiella pneumoniae: 2, Enterococcus: 1). Median duration of antibiotics was 58 days (interquartile range [IQR] 56-84). Median follow-up period post cholangitis was three years (IQR 2-4). Following treatment, 14 patients were successfully delisted from LT waitlist and are presently jaundice-free. Two of the five patients undergoing LT died of sepsis. One patient died awaiting LT.

Timely and aggressive step-up antibiotic regimen may successfully treat IC and prevent/delay LT. HIVA provides a cost-effective and comfortable environment for a child which might improve compliance with intravenous antibiotics.

Prior to 1955, when Morio Kasai first performed the hepatic portoenterostomy procedure which now bears his name, Biliary atresia (BA) was a uniformly fatal disease. Both the Kasai procedure and liver transplantation have markedly improved the outlook for infants with this condition. Although long-term survival with native liver occurs in the minority, survival rates post liver transplantation are high. Most young people born with BA will now survive into adulthood but their ongoing requirements for health care will necessitate their transition from a family-centred paediatric service to a patient-centred adult service. Despite a rapid growth in transition services over recent years and progress in transitional care, transition from paediatric to adult services is still a risk for poor clinical and psychosocial outcomes and increased health care costs. Adult hepatologists should be aware of the clinical management and complications of biliary atresia and the long-term consequences of liver transplantation in childhood. Survivors of childhood illness require a different approach to that for young adults presenting after 18 years of age with careful consideration of their emotional, social, and sexual health. They need to understand the risks of non-adherence, both for clinic appointments and medication, as well as the implications for graft loss. Developing adequate transitional care for these young people is based on effective collaboration at the paediatric-adult interface and is a major challenge for paediatric and adult providers alike in the 21st century. This entails education for patients and adult physicians in order to familiarise them with the long-term complications, in particular for those surviving with their native liver and the timing of consideration of liver transplantation if required. This article focusses on the outcome for children with biliary atresia who survive into adolescence and adult life with considerations on their current management and prognosis.

Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.

The age at Kasai portoenterostomy (KPE) was reported to correlate with the prognosis of patients with biliary atresia (BA) and that a late KPE is bounded to be failure. Herewith, we reported the outcome of patients receiving KPE after day 70 of life. In addition, the prognostic indicators were evaluated.

This was a retrospective analysis and all BA patients receiving KPE after day 70 of life in a tertiary centre between 1980 and 2018 were evaluated.

A total of 164 KPE procedures were performed during the study period and 62 cases were done after day 70 of life which were included in this study. The median follow up period of these patients was 10.6 years (range: 4.5 to 41.5 years). Thirty-nine patients (62.9%) patients were able to achieve jaundice clearance at 6 months after KPE. The NLS rate was 53.2% (n = 33) as recorded at the time of writing. There was no statistical difference in the age at KPE between native liver survivors and patients requiring liver transplant. For complications among the native liver survivors (n = 33), portal hypertension and recurrent cholangitis were found in 63.6% and 30.3% of these patients. There was also no significant difference in the age at KPE between those who developed portal hypertension and recurrent cholangitis (p = 0.451 and p = 0.173 respectively). Regarding the prognostic indicators in predicting NLS, pre-KPE bilirubin, alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were significantly higher among patients requiring liver transplant (p = 0.012, =0.011 and =0.017 respectively). The bilirubin level at 6 months after KPE was also higher among patients who required liver transplant (p = 0.016).

More than half of the BA patients can survive for 10 years with their native liver despite KPE was performed after day 70 of life. However, they have a higher chance to develop BA-related complications. The level of pre-KPE bilirubin and ductal enzymes as well as post-KPE bilirubin are prognostic indicators to predict NLS.

Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of liver development with a focus on cholangiocyte differentiation and how use of technical platforms, including rodent, zebrafish and organoid models, advances our understanding of Biliary Atresia. This is followed by a description of potential pathomechanisms, such as autoimmune responses, inflammation, disturbed apical-basal cell polarity, primary cilia dysfunction as well as beta-amyloid accumulation. Finally, we describe current and emerging diagnostic opportunities and recent translation breakthroughs for Biliary Atresia in the area of emerging therapy development, including immunomodulation and organoid-based systems for liver and bile duct repair.

Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver. The chronic cholangiopathy progresses to cirrhosis, complications of portal hypertension, recurrent cholangitis or hepatobiliary tumors necessitating LT later in life. Other common related health problems include impaired bone health, neuromotor development and quality of life. Only few high-quality trials are available for evidence-based guidance of post-PE adjuvant medical therapy or management of the disease complications. Better understanding of the pathophysiological mechanisms connecting native liver injury to clinical outcomes is critical for development of accurate follow-up tools and novel therapies designed to improve native liver function and survival.