Search Results (93)

Pediatric (neonatal and infantile) jaundice resulting from underlying cholestasis (caused by conjugated hyperbilirubinemia) is always pathological and requires prompt evaluation. Pediatric cholestasis can be caused by medical or surgical factors and, if left untreated, can lead to irreversible liver damage. Timely recognition of pediatric cholestasis and identification of the underlying etiology are paramount to improve outcomes. The broad spectrum of causes potentially underlying pediatric cholestasis requires a multidisciplinary diagnostic approach, and each aspect must be interpreted in the concomitant clinical picture. A liver biopsy is one component of a complex diagnostic puzzle. However, interpreting a liver biopsy performed on a newborn/infant with conjugated/direct hyperbilirubinemia can be a challenging task, as these biopsies are rarely encountered in general hospitals. The aim of this review is to provide a practical and simplified approach to pediatric cholestasis with examples of real clinical cases we have encountered and discuss key features, both histological and clinical, that can help narrow the differential diagnosis and identify treatable causes. Full article

Biliary atresia (BA) is characterized by rapidly progressive hepatic fibrosis with unclear mechanisms. This study aimed to investigate the role of matrix metalloproteinase 7 (MMP7) in this process and its potential for targeted therapy. Serum and liver tissue samples from BA patients were collected to analyze the correlation between MMP7 and liver fibrosis. Gene set enrichment analysis (GSEA) based on GEO datasets was performed to explore MMP7-associated biological processes. Clinical samples were further used to examine the relationship between MMP7 and epithelial–mesenchymal transition (EMT) in biliary epithelial cells (BECs). The effects of MMP7 on BECs and the underlying mechanisms were validated in vitro. Finally, the profibrotic effects and therapeutic potential of MMP7 were explored in chronic BA mice. Results showed that MMP7 was positively correlated with liver fibrosis in BA patients. GSEA revealed that MMP7 was most significantly associated with EMT, which was further validated by EMT scoring in intrahepatic BECs of patients. In vitro, MMP7 induced EMT in BECs by cleaving E-cadherin and promoting β-catenin nuclear translocation. Blockade of MMP7 alleviated EMT and liver fibrosis in BA mice. In conclusion, MMP7 promotes liver fibrosis in BA by driving EMT via the E-cadherin/β-catenin pathway, and targeting MMP7 demonstrates anti-fibrotic effects. Full article

Background: To improve the early recognition of biliary atresia (BA) and timely treatment, this study developed a predictive model integrating combi-elastography, a novel form of elastography, to distinguish biliary atresia from other cholestatic liver diseases (non-BA) in infants. Method: A total of 69 children aged < 60 days with cholestatic hepatitis were retrospectively enrolled. All patients underwent conventional ultrasonography, combi-elastography, and laboratory testing. The variables were selected using logistic regression to construct a nomogram model, and the performance of the model was evaluated. Results: Multifactorial logistic regression analysis indicated that GGT (p = 0.015), the gallbladder morphology (p = 0.017), and the fibrosis index of the combi-elastography (p = 0.017) could be used as independent predictors to differentiate BA from other causes of cholestasis. A nomogram model constructed with these three indexes showed better performance, with an area under the operating characteristic curve (AUC) of 0.887 (0.823, 0.952) (p < 0.001), sensitivity of 86.4%, and specificity of 76.0%. Using 1000 Bootstrap resamples for internal validation of the model, the predictive effect of the nomogram model to identify biliary atresia from other cholestatic liver diseases was in good agreement with the actual situation. Decision-curve analysis showed that the use of the nomogram model to predict biliary atresia gained more clinical value at a risk threshold of 0.10–0.80. Conclusion: The nomogram constructed integrating combi-elastography and liver function indices shows promising value for predicting the risk for developing biliary atresia. Full article

Background: The nutrition support of children with biliary atresia after liver transplant is affected by multiple factors, and a connection between these factors and conditions present before transplant can potentially make the nutrition support more challenging. We aim to assess the adequacy of nutrition support, specifically energy and protein, during the first week of admission to the Pediatric Intensive Care Unit (PICU) in children after liver transplant secondary to biliary atresia. Methods: We performed a retrospective cohort study of 138 patients [13.9 median (9–33.4) IQR months; 62% female] with a diagnosis of biliary atresia admitted to the PICU after liver transplantation at Texas Children’s Hospital over a 14-year study period. We obtained nutrition adequacy of enteral and parenteral nutrition support for the first week after transplant during their PICU admission. Results: Goal adequacy was reached at the end of the first week of admission when combined enteral and parenteral nutrition support was provided (median 98% for energy and 101% for protein). Infants achieved significantly higher adequacies than older children during the first week (136% < 1 year vs. 0% > 1 year, p < 0.001 for calories, and 157% < 1 year vs. 0% > 1 year for protein; p < 0.01). Conclusions: These findings highlight the complex nutritional challenges faced by this population, and strategies are needed to meet the unique needs of children after liver transplantation. Full article

Background: Biliary atresia (BA) is a rare, immune-mediated cholangiopathy in children and a leading cause of neonatal cholestasis and pediatric liver transplantation (LT). Gamma-glutamyl transpeptidase (GGT) is commonly elevated in BA and is used as a diagnostic marker; however, recent studies have suggested that a subset of BA patients present with normal or low GGT levels, potentially indicating a more severe disease course. Methods: This retrospective study evaluated the prognostic value of serum GGT levels in 47 children diagnosed with BA at a single center over 15 years. Patients were stratified by GGT levels at diagnosis, and outcomes were compared, including survival with native liver, need for LT, and mortality. GGT thresholds of 200 U/L and 300 U/L were used to define normal and elevated levels. Results: The study found that 12% of patients had normal or low GGT at diagnosis. Still, there were no statistically significant differences in age at diagnosis, severity of liver fibrosis, age at Kasai portoenterostomy (KPE), or overall outcomes between low and high GGT groups. Although patients with lower GGT tended to require LT at a younger age, this difference was not significant. Receiver operating characteristic (ROC) curve analysis showed that GGT levels at diagnosis, before, and after KPE were not reliable predictors of outcome. Conclusions: The findings contrast with some previous reports suggesting that low GGT is associated with a worse prognosis. Low GGT level alone should not delay diagnosis or surgical intervention in suspected BA. Early referral for KPE remains critical, and patients with low GGT may benefit from earlier LT evaluation. Larger, multicenter studies are needed to clarify the prognostic role of GGT in BA. Full article

Cholangiopathies encompass a wide range of chronic liver diseases that target biliary epithelial cells, leading to significant morbidity and mortality due to their progressive nature, limited treatment options, and complex clinical management. Currently, clinically validated biomarkers capable of distinguishing obstructive cholangiopathies, such as biliary atresia (BA), from other cholangiopathies are lacking, hindering timely intervention. RNA-binding proteins (RBPs) have been increasingly linked to human diseases but their roles in cholangiopathies remain underexplored. We assessed the expression of the RBP epithelial splicing regulatory protein 1 (ESRP1) in murine models of cholangiopathies and in the human system. Our findings demonstrate that ESRP1 is highly and specifically expressed in cholestatic liver injury models, including bile duct-ligated, diethoxycarboncyl-1,4-dihydrocollidine-treated, and Mdr2^−/− mice when compared with other liver injury models. Importantly, ESRP1 is markedly elevated in the livers of patients with BA and cystic fibrosis-related liver disease, localizing to cholangiocytes and peri-biliary hepatic cells, but is minimal in primary sclerosing cholangitis and primary biliary cholangitis. Moreover, patient-derived BA organoids and biliatresone-treated healthy organoids also display ESRP1 expression. Bioinformatics analysis further implicates ESRP1 in key cholangiopathy-associated pathways, warranting deeper mechanistic investigation. Thus, ESRP1 holds potential as a molecular marker for obstructive cholangiopathies, warranting further mechanistic studies. Full article

Many familial diseases are caused by genetic accidents, which affect the genome and its epigenetic environment, summarized as an interaction network between genes. We wish to study the existence or absence of robustness for such genetic interaction networks centered on the gene SP1 and involved in three familial diseases: familial angioedema, osteogenesis imperfecta, and biliary atresia. The updating of gene states at the vertices of the interaction graph of the genetic network (1 if a gene is activated, 0 if it is inhibited) can be performed in multiple ways that have been well-studied over the last 20 years: parallel, block-parallel, sequential, block-sequential, random, etc. We add to these classic updating modes two new ones, the intricate and the state-dependent. We have studied the robustness of three particular interaction graphs related to the familial diseases chosen as examples. The comparison of the interaction graphs and dynamics of the chosen familial diseases of different etiology shows common points in their interaction graphs and similarities in their dynamics according to their expression clock. Full article

Background/Objectives: This study conducted a secondary and integrative analysis of qualitative data on adolescents and young adults (AYAs) with biliary atresia who survive with their native livers. These individuals struggle with independence and self-care due to prolonged parental involvement. Prior studies have insufficiently clarified how AYAs and parents jointly navigate daily responsibility transitions during this period. Therefore, we aimed to elucidate this process and develop a practical model to support nursing care. Methods: Semi-structured interview data from eight adolescent–parent dyads (one male and seven females, aged 17–25; one father and seven mothers, aged 40–60) were reanalyzed using the modified grounded theory approach. By reframing the analytical focus on dyadic interactions, four transition phases were identified, which were then integrated with the findings of two prior studies to construct an integrative process model. Results: The transition comprised four phases: (1) parent-led recuperation, (2) a vicious cycle of control and rebellion, (3) passing the axis of responsibility, and (4) aligning the parent–child rhythm to create a patient-centered life. The transition processes were shaped by changes in cognition and behavior. The model illustrates mutual adaptation through communication, negotiation, and reflection, identifying opportunities for nursing intervention. Conclusions: This process model offers a practical framework for nurses to assess readiness for care transitions, support transitional role shifts, and co-develop care strategies. The model provides insights into relationship-based communication and shared decision-making in transitional care by capturing the relational dynamics between AYAs and their parents. Full article

Cholangiopathies, a diverse group of diseases affecting the biliary tract, are characterized by the activation of cholangiocytes, fibrosis, and inflammation. Recent research has identified extracellular vesicles (EVs) as crucial mediators of communication within the hepatobiliary system. This review aims to explore the impact of EVs on cholangiocyte behavior and their role in disease development. EVs originating from cholangiocytes, hepatocytes, and immune cells carry a variety of molecules, including non-coding RNAs, proteins, and lipids, which influence immune responses, fibrosis, and epithelial repair. Specifically, EVs released by activated or senescent cholangiocytes can worsen inflammation and fibrosis by delivering molecules such as lncRNA H19, miR-21, and damage-associated molecular patterns (DAMPs) to hepatic stellate and immune cells. Additionally, the polarity and content of EVs are influenced by specific subcellular domains of cholangiocytes, indicating distinct signaling functions. In conditions such as primary sclerosing cholangitis (PSC), cholangiocarcinoma (CCA), and biliary atresia, EVs play a role in disease progression and offer potential as non-invasive biomarkers and therapeutic targets. This review underscores the importance of in-depth profiling and validation of EVs to fully utilize their diagnostic and therapeutic capabilities. Overall, EV-mediated signaling is a critical mechanism in cholangiopathies, providing a new avenue for understanding disease progression and developing precision medicine approaches. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

Liver fibrosis is a frequent pathological outcome of long-term liver diseases, arising from sustained damage to the liver. Two main types of liver damage can trigger fibrotic progression: hepatocellular injury, often caused by viral infections, alcohol, or metabolic disorders, and cholestatic injury, associated with impaired bile flow due to autoimmune or congenital conditions. Despite diverse etiologies, liver fibrosis exhibits conserved biological processes, including hepatocyte death, chronic inflammation, disruption of epithelial or endothelial barriers, and excessive deposition of extracellular matrix (ECM) components. These coordinated events reflect the complex interplay among parenchymal damage, immune activation, and fibrogenic signaling pathways. If unresolved, fibrosis may progress to cirrhosis, liver failure, or hepatocellular carcinoma. In the pursuit of non-invasive biomarkers for early detection and monitoring of fibrosis, extracellular vesicles (EVs) have garnered significant attention. Among the diverse cargoes within EVs, microRNAs (miRNAs) have emerged as particularly promising due to their stability, disease-specific expression patterns, and involvement in fibrogenic signaling. This review explores the role of EV-associated miRNAs in liver fibrosis, highlighting key candidates implicated in hepatocellular and cholestatic injury and their clinical potential as diagnostic and prognostic biomarkers, with special focus on MAFLD/MASH, primary sclerosing cholangitis, primary biliary cholangitis, and biliary atresia as representatives. Full article

Objectives: The aim of this study was to investigate the diagnostic value of a scoring system based on diffusion tensor imaging (DTI) and blood biochemistry tests for biliary atresia (BA) in infants. Methods: Seventy-four patients who had undergone DTI and blood biochemistry tests were included in this study. Among them, 51 (36 BA patients and 15 non-BA patients) were assigned to the training cohort, and 23 (14 BA patients and 9 non-BA patients) were assigned to the validation cohort. The characteristics that significantly differed between the groups in the training cohort were used to develop a scoring system for predicting the presence or absence of BA through binary logistic regression analysis. The scoring system was subsequently validated in the validation cohort, and its diagnostic performance was assessed with receiver operating characteristic curve analysis. Results: The mean apparent diffusion coefficient values of the hepatic right and caudate lobes and the serum levels of gamma glutamyl transpeptidase were selected for constructing the scoring system. The accuracy, sensitivity, and specificity of the system in predicting BA were 82.35%, 91.67% and 60%, respectively, in the training cohort and 95.65%, 100% and 88.89%, respectively, in the validation cohort. The areas under the receiver operating characteristic curve in the training cohort and validation cohort for predicting BA were 0.87 and 0.94 (p ≤ 0.001 each), respectively. Conclusions: We developed a relatively noninvasive scoring system for diagnosing BA according to the results of DTI and blood biochemistry tests, which demonstrated good performance and may be a potential method for differentiating BA in infants. Full article

Rotavirus (RV) is the most common cause of severe acute gastroenteritis (AGE) in children under five years of age. This review summarizes current knowledge on RV infections, with a particular focus on viral structure, pathophysiological mechanisms, and age-dependent clinical presentation. Special attention is given to systemic manifestations, including central nervous system involvement, autoimmune responses such as type 1 diabetes and celiac disease, and rare associations with biliary atresia. The mechanisms of RV-induced diarrhea and vomiting are discussed in detail. Clinical severity scoring systems—such as the Vesikari and Clark scales—and dehydration assessment tools—the Clinical Dehydration Scale (CDS) and the Dehydration: Assessing Kids Accurately (DHAKA) score—are compared. The review highlights differences in disease course between children under and over five years, emphasizing that RV is not limited to early childhood. A major section addresses the global effectiveness of vaccination programs, their role in reducing disease burden, coverage challenges, and decreased efficacy in low-income countries. Particular focus is placed on high-risk groups, including preterm and immunocompromised infants. Full article

Background/Objectives: Biliary atresia (BA) is the most common etiology for pediatric liver transplantation (LT). However, whether a previous Kasai hepatoportoenterostomy (KP) and its timing influence the outcomes of BA patients who undergo LT remains controversial. Methods: Pediatric patients with BA who underwent LT at Beijing Friendship Hospital, Capital Medical University, between June 2013 and November 2022 were recruited. The patients were divided into non-KP, early-KP (before 90 days of life), and late-KP subgroups. The clinical data were compared among the groups. A nomogram to predict the 1-, 3-, and 5-year graft survival probabilities based on a multivariate Cox model was constructed and validated. Results: Among the 475 BA patients, the no-KP group accounted for 31.8%, the early KP for 60.4%, and the late KP for 7.8%, respectively. The incidences of LT complications were comparable among the groups. From the multivariate Cox analyses, an intensive care unit (ICU) stay and bleeding were identified as the independent risk factors for postoperative patient survival, and the LT type, graft type, vascular complications, and biliary complications were those for graft survival. A nomogram for graft survival was constructed, with a C-index of 0.82, and areas under the curves (AUCs) of 0.829, 0.824, and 0.824 for the 1-, 3-, and 5-year survival nomograms, respectively. The calibration and decision curve analysis (DCA) curves showed good discrimination ability and clinical applicability. A risk classification system was further developed, and the Kaplan–Meier curves demonstrated high discrimination between the high- and low-risk groups (p < 0.0001). Conclusions: A previous KP has no impact on patients or graft survival after LT in BA patients. The established nomogram may be helpful for counseling BA patients about their clinical prognosis after LT. Full article

Ciliopathies are disorders that affect primary or secondary cellular cilia or structures associated with ciliary function. Primary cilia (PC) are essential for metabolic regulation and embryonic development, and pathogenic variants in cilia-related genes are linked to several pediatric conditions, including renal-hepatic diseases and congenital defects. Biliary atresia (BA) is a progressive infantile cholangiopathy and the leading cause of pediatric liver transplantation. Although the exact etiology of BA remains unclear, evidence suggests a multifactorial pathogenesis influenced by both genetic and environmental factors. Patients with BA and laterality defects exhibit genetic variants associated with ciliopathies. Interestingly, even isolated BA without extrahepatic anomalies presents morphological and functional ciliary abnormalities, suggesting that environmental triggers may disrupt the ciliary function. Among these factors, hypoxia has emerged as a potential modulator of this dysfunction. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a central role in hepatic responses to oxygen deprivation, influencing bile duct remodeling and fibrosis, which are key processes in BA progression. This review explores the crosstalk between hypoxia and hepatic ciliopathies, with a focus on BA. It discusses the molecular mechanisms through which hypoxia may drive disease progression and examines the therapeutic potential of targeting hypoxia-related pathways. Understanding how oxygen deprivation influences ciliary function may open new avenues for treating biliary ciliopathies and improving patient outcomes. Full article