|
1
|
Jessen AKG, Helt TW, Johansen LS, Gaardskær RN, Heiring C, Kvistgaard H, Madsen MA, Simonsen JA, Møller S, Christensen VB, Borgwardt L. Thresholds for conjugated hyperbilirubinaemia and hepatobiliary scintigraphy in biliary atresia: A 12-year national follow-up. Acta Paediatr 2025; 114:1143-1151. [PMID: 39648320 DOI: 10.1111/apa.17536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/05/2024] [Accepted: 11/28/2024] [Indexed: 12/10/2024]
Abstract
AIM To investigate liver biochemistry in infants screened for biliary atresia (BA) at the time of hepatobiliary scintigraphy (HS) and to evaluate the effect of change in threshold for HS. METHODS Infants born from 2010 to 2021, who underwent HS <6 months postpartum for BA, were included and data sourced from electronic medical records. The change in threshold in 2018 from ≥20 (and/or if conjugated bilirubin exceeds 20% of total bilirubin) to ≥17 μM (regardless of total bilirubin) was evaluated. RESULTS In the cohort of 635 infants, 48 had BA, 247 had AATD, and the remaining 343 were categorised as 'other'. After the threshold adjustment, HS timing was unaffected (p = 0.27), but the annual HS rate rose from 39 to 87, yet evaluations following the new guideline only accounted for 12%. All liver parameters were elevated in the BA group compared with the additional groups (p < 0.001). Amongst the 104 patients with non-excretory HS, gamma-glutamyl transferase (p < 0.001) and alanine aminotransferase (p = 0.002) remained elevated for BA. The lowest conjugated bilirubin measured in BA children was 36 μM. CONCLUSION After threshold change, HS use increased without earlier BA diagnostics, but most were not due to the new guideline. Alanine aminotransferase and gamma-glutamyl transferase should be considered in BA diagnostics.
Collapse
Affiliation(s)
- Anna Kajsa G Jessen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Thora W Helt
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lars S Johansen
- Department of Paediatric Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Rasmus N Gaardskær
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Christian Heiring
- Department of Neonatal and Pediatric Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Helene Kvistgaard
- Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Michael A Madsen
- Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Jane A Simonsen
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Vibeke B Christensen
- Department of Paediatric Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Comparative Pediatrics and Nutrition, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lise Borgwardt
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| |
Collapse
|
|
2
|
Prediction of Native Liver Survival in Patients With Biliary Atresia 20 Years After the Kasai Procedure. J Pediatr Surg 2025; 60:162158. [PMID: 39837209 DOI: 10.1016/j.jpedsurg.2025.162158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/12/2024] [Accepted: 01/03/2025] [Indexed: 01/23/2025]
Abstract
OBJECTIVE To establish risk models for long-term native liver survival (NLS) in patients with biliary atresia. METHODS In this retrospective study, we analyzed data from 1792 patients registered in the Japanese Biliary Atresia Registry. Using multivariate logistic regression, we created predictive models for NLS at 1, 5, 10, 15, and 20 years postoperatively. Variables at the first year of age and those at 1 and 5 years postoperatively were used. The variables used in this model were selected using a forward-backward stepwise selection method. The models were further assessed using C-statistics of internal validation with 1000 bootstrapping resamples. RESULTS The models using only variables at the first year of age showed insufficient predictive ability. The variables used in the model for NLS at 20 years postoperatively included the age at Kasai procedure, high levels of gamma-glutamyltranspeptidase at 1 year postoperatively, and low levels of cholinesterase at 5 years postoperatively. The models with internally validated C-statistics greater than 0.8 were as follows: NLS at 5 years postoperatively based on the variables at 1 year postoperatively (internally validated C-statistics: 0.88), at 10 years postoperatively based on the variables at 1 year postoperatively (0.86), and at 20 years postoperatively based on the variables at 1 year (0.81) and 5 years (0.83) postoperatively. CONCLUSION Overall, we developed satisfactory risk models for NLS up to 20 years postoperatively using variables up to 5 years postoperatively.
Collapse
|
|
3
|
Curran IL, Cowles RA. Preoperative evaluation of biliary atresia. Semin Pediatr Surg 2024; 33:151475. [PMID: 39892001 DOI: 10.1016/j.sempedsurg.2025.151475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/07/2025] [Indexed: 02/03/2025]
Abstract
Biliary atresia can be a challenging diagnosis to make as there is no single definitive diagnostic laboratory or imaging study available and no single agreed upon diagnostic algorithm. The purpose of this article is to review the complex puzzle of clinical, laboratory, and imaging studies that aid in the evaluation of infants suspected of having biliary atresia. We have reviewed historical and current manuscripts and society guidelines, added our own experience in evaluating infants for biliary atresia, and then summarized the findings to provide a concise review of what we feel is the modern approach to diagnosis of biliary atresia.
Collapse
Affiliation(s)
- Isabelle Lane Curran
- Division of Pediatric Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520, USA
| | - Robert A Cowles
- Division of Pediatric Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520, USA.
| |
Collapse
|
|
4
|
Kohlmaier B, Tichy H, Blatterer J, Till H, Schlagenhauf A, Knisely AS. Extrahepatic biliary atresia and normal-range serum gamma-glutamyltranspeptidase activity: A case report. JPGN REPORTS 2024; 5:533-537. [PMID: 39610416 PMCID: PMC11600354 DOI: 10.1002/jpr3.12131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/31/2024] [Accepted: 09/02/2024] [Indexed: 11/30/2024]
Abstract
An infant with biliary atresia had normal-range ('low') serum gamma-glutamyltranspeptidase (GGT) activity, exceptional because GGT generally is elevated in biliary atresia. Mechanisms underlying low-GGT cholestasis in biliary atresia are not defined, but the phenomenon is associated with worse clinical outcome. Testing in our patient revealed no variants in genes mutated in several disorders also associated with poor prognosis and with low-GGT cholestasis; indeed, at age 14 months she has stable disease with unremarkable biomarker values. Nonetheless, we recommend extended investigations in such patients, including genetic testing, to detect coexistent disorders and to expand understanding of GGT in biliary atresia.
Collapse
Affiliation(s)
- Benno Kohlmaier
- Department of Pediatrics and Adolescent Medicine, Division of General PediatricsMedical University of GrazGrazAustria
| | - Heidelis Tichy
- Diagnostic and Research Institute of Human GeneticsMedical University of GrazGrazAustria
| | - Jasmin Blatterer
- Diagnostic and Research Institute of Human GeneticsMedical University of GrazGrazAustria
| | - Holger Till
- Department of Paediatric and Adolescent SurgeryMedical University of GrazGrazAustria
| | - Axel Schlagenhauf
- Department of Pediatrics and Adolescent Medicine, Division of General PediatricsMedical University of GrazGrazAustria
| | - A. S. Knisely
- Diagnostic and Research Institute of PathologyMedical University of GrazGrazAustria
| |
Collapse
|
|
5
|
Toh Q, Chen Y, Lee YY, Mali VP, Choo SC, Chiang LW. Simple biliary atresia score-a validated diagnostic aid for infantile cholestasis. Pediatr Surg Int 2024; 40:212. [PMID: 39085697 DOI: 10.1007/s00383-024-05785-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2024] [Indexed: 08/02/2024]
Abstract
PURPOSE The workup of jaundiced infants may be variable and protracted, thereby delaying the diagnosis and timely intervention for biliary atresia (BA). This potentially leads to inferior outcomes. We developed a practical score to stratify infantile cholestasis according to the risk of having BA. METHOD The score (0-7) [gallbladder length ≤ 15 mm (+ 1), common bile duct (CBD) diameter < 0.5 mm(+ 1), pre-portal vein (PV) echogenicity(+ 1), direct-to-total bilirubin ratio (D/T) ≥ 0.7(+ 2), and gamma-glutamyl transferase (GGT) ≥ 200 IU/L(+ 2)] are derived from logistic regression of data from a retrospective cohort of cholestatic infants (n = 58, 41 BA) in our institution. It was then validated with a separate retrospective cohort (n = 28, 17 BA) from another institution. Final diagnoses were as per intraoperative cholangiogram (IOC) and liver histopathology. RESULTS A cutoff score of ≥ 3 diagnosed BA with 100% and 94% sensitivity in the derivative cohort (area under receiver operating characteristic curve, AUROC 0.869) and validation cohort (AUROC 0.807), respectively. D/T ratio was the most sensitive (93%) and CBD diameter was the most specific (88%) parameter. The score accurately predicted non-BA in 11(65%) and 7(63%) infants in the derivative and validation cohorts, respectively, with one missed BA in the latter. CONCLUSION We propose a validated, simple, yet sensitive diagnostic score to risk-stratify cholestatic infants, aiming to expedite definitive management of BA.
Collapse
Affiliation(s)
- Qi Toh
- Department of Pediatric Surgery, KK Women's and Children's Hospital, No. 100, Bukit Timah Road, Singapore, 229899, Singapore
| | - Yong Chen
- Department of Pediatric Surgery, KK Women's and Children's Hospital, No. 100, Bukit Timah Road, Singapore, 229899, Singapore
| | - Yang Yang Lee
- Department of Pediatric Surgery, National University Hospital, Singapore, Singapore
| | | | - Suet Cheng Choo
- Department of Pediatric Surgery, KK Women's and Children's Hospital, No. 100, Bukit Timah Road, Singapore, 229899, Singapore
| | - Li Wei Chiang
- Department of Pediatric Surgery, KK Women's and Children's Hospital, No. 100, Bukit Timah Road, Singapore, 229899, Singapore.
| |
Collapse
|
|
6
|
Zhao Y, Wang A, Wang D, Sun D, Zhao J, Zhang Y, Hua K, Gu Y, Li S, Liao J, Wang P, Sun J, Huang J. Development of a diagnostic model for biliary atresia based on MMP7 and serological tests using machine learning. Pediatr Surg Int 2024; 40:203. [PMID: 39030361 DOI: 10.1007/s00383-024-05740-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/09/2024] [Indexed: 07/21/2024]
Abstract
OBJECTIVE To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). METHODS A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. RESULTS A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. CONCLUSION Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.
Collapse
Affiliation(s)
- Yong Zhao
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - An Wang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Dingding Wang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
| | - Dayan Sun
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Jiawei Zhao
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yanan Zhang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Kaiyun Hua
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yichao Gu
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Shuangshuang Li
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Junmin Liao
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Peize Wang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Jie Sun
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Jinshi Huang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
| |
Collapse
|
|
7
|
Zhang Y, Li T, Wang T, Ji Q, Zhan J. Comparison for the diagnostic performance of early diagnostic methods for biliary atresia: a systematic review and network meta-analysis. Pediatr Surg Int 2024; 40:146. [PMID: 38822892 DOI: 10.1007/s00383-024-05730-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. METHODS We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. RESULTS A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. CONCLUSION MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.
Collapse
Affiliation(s)
- Yanran Zhang
- Clinical School of Paediatrics, Tianjin Medical University, Tianjin, 300400, China
| | - Tengfei Li
- Clinical School of Paediatrics, Tianjin Medical University, Tianjin, 300400, China
| | - Tong Wang
- Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300192, China
| | - Qi Ji
- Clinical School of Paediatrics, Tianjin Medical University, Tianjin, 300400, China
| | - Jianghua Zhan
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, 300134, China.
| |
Collapse
|
|
8
|
Fu M, Guo Z, Chen Y, Lamb JR, Zhong S, Xia H, Wen Z, Zhang R. Proteomics Defines Plasma Biomarkers for the Early Diagnosis of Biliary Atresia. J Proteome Res 2024; 23:1744-1756. [PMID: 38569191 PMCID: PMC11077583 DOI: 10.1021/acs.jproteome.3c00873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 03/08/2024] [Accepted: 03/19/2024] [Indexed: 04/05/2024]
Abstract
Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of pediatric patients with BA. Herein, we performed proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) to explore potential biomarkers for the early diagnosis of BA compared to other non-BA jaundice cases. Consequently, we detected and validated differential protein expression in the plasma of patients with BA compared to the plasma of patients with intrahepatic cholestasis. Bioinformatics analysis revealed the enriched biological processes characteristic of BA by identifying the differential expression of specific proteins. Signaling pathway analysis revealed changes in the expression levels of proteins associated with an alteration in immunoglobulin levels, which is indicative of immune dysfunction in BA. The combination of polymeric immunoglobulin receptor expression and immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), as revealed via machine learning, provided a useful early diagnostic model for BA, with a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and area under the curve value of 0.944. Thus, our study identified a possible effective plasma biomarker for the early diagnosis of BA and could help elucidate the underlying mechanisms of BA.
Collapse
Affiliation(s)
- Ming Fu
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| | - Zhipeng Guo
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| | - Yan Chen
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
- Faculty
of Medicine, Macau University of Science
and Technology, Avenida
Wai Long, Taipa, Macau China
| | - Jonathan R. Lamb
- Department
of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United
Kingdom
| | - Suirui Zhong
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| | - Huimin Xia
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| | - Zhe Wen
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| | - Ruizhong Zhang
- Provincial
Key Laboratory of Research in Structure Birth Defect Disease and Department
of Pediatric Surgery, Guangzhou Women and Children’s Medical
Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China
| |
Collapse
|
|
9
|
Kong F, Dong R, Chen G, Sun S, Yang Y, Jiang J, Meng L, Chen H, Zhu J, Zheng S. Progress in Biomarkers Related to Biliary Atresia. J Clin Transl Hepatol 2024; 12:305-315. [PMID: 38426193 PMCID: PMC10899875 DOI: 10.14218/jcth.2023.00260] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 12/12/2023] [Accepted: 01/02/2024] [Indexed: 03/02/2024] Open
Abstract
Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.
Collapse
Affiliation(s)
- Fanyang Kong
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Rui Dong
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Gong Chen
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Song Sun
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Yifan Yang
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Jingying Jiang
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Lingdu Meng
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Huifen Chen
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Jiajie Zhu
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| |
Collapse
|
|
10
|
Ali KM, Zalata KR, Barakat T, Elzeiny SM. Pathologic approach to Neonatal cholestasis with a simple scoring system for biliary atresia. Virchows Arch 2024; 484:93-102. [PMID: 38008855 PMCID: PMC10791702 DOI: 10.1007/s00428-023-03704-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/03/2023] [Accepted: 11/08/2023] [Indexed: 11/28/2023]
Abstract
A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1-191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.
Collapse
Affiliation(s)
- Khadiga M Ali
- Pathology Department, Faculty of Medicine, Mansoura University, Elgomhoria Street, Mansoura, Eldakahliya, 35516, Egypt.
| | - Khaled R Zalata
- Pathology Department, Faculty of Medicine, Mansoura University, Elgomhoria Street, Mansoura, Eldakahliya, 35516, Egypt
| | - Tarik Barakat
- Gastroenterology and Hepatology Unit, Mansoura Faculty of Medicine, Mansoura Children Hospital, Mansoura, Egypt
| | - Sherine M Elzeiny
- Gastroenterology and Hepatology Unit, Mansoura Faculty of Medicine, Mansoura Children Hospital, Mansoura, Egypt
| |
Collapse
|
|
11
|
Gong Z, Lin L, Lu G, Wan C. Development and validation of a model for early diagnosis of biliary atresia. BMC Pediatr 2023; 23:549. [PMID: 37907911 PMCID: PMC10617173 DOI: 10.1186/s12887-023-04370-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 10/06/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND AND AIMS Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation. METHODS Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses. RESULTS Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA. CONCLUSION A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.
Collapse
Affiliation(s)
- Zongrong Gong
- Department of Pediatrics, West China Second Hospital, Sichuan University and Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, No 20, 3rd Section of Renmin South Road, Chengdu, 610041, People's Republic of China
- Department of Respiration, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Lin Lin
- Department of Respiration, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Gen Lu
- Department of Respiration, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China
| | - Chaomin Wan
- Department of Pediatrics, West China Second Hospital, Sichuan University and Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, No 20, 3rd Section of Renmin South Road, Chengdu, 610041, People's Republic of China.
- Department of Pediatric Infectious Disease, West China Women's and Children's Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Second University Hospital, Sichuan University, Ministry of Education, No 20, 3rd section of Renmin South Road, 610041, Chengdu, P.R. China.
| |
Collapse
|
|
12
|
Lee CS, Ni YH, Chen HL, Wu JF, Hsu HY, Chien YH, Lee NC, Hwu WL, Yen TA, Chua HH, Chen YJ, Wang YL, Chang MH. A Pilot Study of Biliary Atresia Newborn Screening Using Dried Blood Spot Matrix Metalloproteinase-7. J Pediatr Gastroenterol Nutr 2023; 76:418-423. [PMID: 36946999 DOI: 10.1097/mpg.0000000000003701] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
OBJECTIVES Timely diagnosis is a critical challenge and is associated with improved survival of biliary atresia (BA) patients. We aimed to measure matrix metalloproteinase-7 (MMP-7) levels in BA patients within 3 days of birth using the dried blood spot (DBS) method and evaluate its potential as a screening tool. METHODS The study enrolled 132 patients, including 25 patients diagnosed with BA and 107 non-BA patients with other congenital or perinatal conditions from the National Taiwan University Children Hospital. The stored DBS samples collected from 48 to 72 hours of life were retrieved from newborn screening centers. MMP-7 on the DBS was quantified using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS The MMP-7 levels of BA patients on the DBS were significantly higher than those of non-BA patients (19.2 ± 10.4 vs 5.6 ± 2.7 ng/mL, P value < 0.0001). MMP-7 levels in non-BA patients, including 5 patients with hepatobiliary structural anomaly, 9 patients with intrahepatic cholestasis, and 93 patients with other perinatal diseases, were 11.6 ± 4.2 ng/mL, 6.9 ± 3.0 ng/mL, and 5.2 ± 2.1 ng/mL, respectively. The DBS MMP-7 level showed good accuracy for identifying BA, with an area under the curve of 93.7% [95% confidence interval (CI): 87.7%-99.7%]. The MMP-7 cutoff at 8.0 ng/mL showed a sensitivity of 92.0% (95% CI: 75.0%-98.6%) and specificity of 92.5% (95% CI: 85.9%-96.1%) for detecting BA from other congenital or perinatal diseases. CONCLUSIONS MMP-7 DBS analysis can be used to distinguish BA from other conditions as early as 3 days of age.
Collapse
Affiliation(s)
- Chee-Seng Lee
- From the Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsuan Ni
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Huey-Ling Chen
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- the Department and Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Feng Wu
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hong-Yuan Hsu
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yin-Hsiu Chien
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- the Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ni-Chung Lee
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- the Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Wuh-Liang Hwu
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- the Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-An Yen
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Huey-Huey Chua
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Ju Chen
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
| | - Yu-Lin Wang
- Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu, Taiwanthe
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Mei-Hwei Chang
- the Department of Pediatrics, National Taiwan University Hospital and Children's Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
13
|
Karbasian F, Mashhadiagha A, Anbardar MH, Ataollahi M, Dehghani SM, Honar N, Haghighat M, Imanieh MH, Sayadi M, Shahramian I, Aghsam A, Hosseini A, Mahadavi Mortazavi SM, Darban B, Avazpour A, Mirrahimi B, Ruzbahani AK, Tadayon A. Questioning Diagnostic Value of Serum Matrix Metalloproteinase 7 for Biliary Atresia. J Clin Exp Hepatol 2023; 13:265-272. [PMID: 36950494 PMCID: PMC10025680 DOI: 10.1016/j.jceh.2022.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 10/01/2022] [Indexed: 12/03/2022] Open
Abstract
Background Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population. Methods and materials In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany). Results 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13 ng/mL in the BA group and 1.85 ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA. Conclusion Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended.
Collapse
Key Words
- ALP, Alkaline phosphatase
- BA, Biliary atresia
- DB, Direct bilirubin
- GGT, Gamma-glutamyl transferase
- KPE, Kasai portoenterostomy
- LT, Liver transplantation
- MMP7, Matrix metalloproteinase 7
- MRCP, Magnetic resonance cholangiopancreatography
- PFIC, Progressive familial intrahepatic cholestasis
- PIBD, Paucity of interlobular bile ducts
- TSB, Total serum bilirubin
- biliary atresia
- cholestasis
- kasai portoenterostomy
- matrix metalloproteinase 7
Collapse
Affiliation(s)
- Fereshteh Karbasian
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirali Mashhadiagha
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Maryam Ataollahi
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed M. Dehghani
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Naser Honar
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Haghighat
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad H. Imanieh
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehrab Sayadi
- Medical Faculty, Kazerun Branch, Islamic Azad University, Kazerun, Iran
| | - Iraj Shahramian
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Aghsam
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirhossein Hosseini
- Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Behnaz Darban
- Department of Pediatrics, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Abbas Avazpour
- Department of Pediatrics, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Bahador Mirrahimi
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arian K. Ruzbahani
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Ali Tadayon
- Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
14
|
Zhang K, Tang Y, Liu R, Zheng Z, Tang C, Liu Y, Jin Z. Intraoperative hepatic subcapsular spider-like telangiectasia sign for the definitive diagnosis of biliary atresia. BMC Pediatr 2023; 23:63. [PMID: 36747150 PMCID: PMC9900992 DOI: 10.1186/s12887-022-03831-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 12/29/2022] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To evaluate the accuracy of intraoperative hepatic subcapsular spider-like telangiectasia (HSST) sign for differentiating biliary atresia (BA) from other causes of hepatic cholestasis. METHODS The data of 69 patients with jaundice treated from January 2019 to December 2021 were retrospectively analyzed. Based on intraoperative cholangiography (IOC), the patients were divided into two groups: the BA group (n = 49) and the non-BA group (n = 20). The biochemistry tests, liver ultrasound, liver stiffness value and HSST sign of the two groups were compared. RESULTS The incidence of abnormal gallbladder, elevated γ-glutamyl transpeptidase (γ-GGT) > 182.0U/L and abnormal liver stiffness (> 6.4 kPa) in BA group were significantly higher than those in non-BA group (P < 0.001). The HSST sign was present in all BA patients and not found in non-BA group. The area under receiver operating curve of direct bilirubin(DBIL), γ-GGT, abnormal gallbladder, liver stiffness value and HSST sign were 0.53, 0.84, 0.78, 0.96, and 1.00, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of HSST sign in the diagnosis of BA were all 100%. CONCLUSION Presence of HSST sign on diagnostic laparoscopy is highly suggestive of BA.It can be used in the differential diagnosis of BA and non-BA. LEVEL OF EVIDENCE Level III.
Collapse
Affiliation(s)
- Kaizhi Zhang
- grid.413390.c0000 0004 1757 6938Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 China ,Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000 China
| | - Yan Tang
- grid.411292.d0000 0004 1798 8975Clinical Medical College, Chengdu University, Chengdu, 610081 China
| | - Rui Liu
- grid.413390.c0000 0004 1757 6938Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 China ,Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000 China
| | - Zebing Zheng
- grid.413390.c0000 0004 1757 6938Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 China ,Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000 China
| | - Chengyan Tang
- grid.413390.c0000 0004 1757 6938Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 China ,Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000 China
| | - Yuanmei Liu
- grid.413390.c0000 0004 1757 6938Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 China ,Department of Pediatric Surgery, Guizhou Children’s Hospital, Zunyi, 563000 China
| | - Zhu Jin
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China. .,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, 563000, China.
| |
Collapse
|
|
15
|
Findings in percutaneous trans-hepatic cholecysto-cholangiography in neonates and infants presenting with conjugated hyperbilirubinemia: emphasis on differential diagnosis and cholangiographic patterns. BMC Pediatr 2023; 23:22. [PMID: 36639762 PMCID: PMC9840309 DOI: 10.1186/s12887-022-03816-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 12/21/2022] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Biliary atresia (BA) is one of the causes of conjugated hyperbilirubinemia in infants which if untreated leads to end-stage liver disease and death. Percutaneous Trans-hepatic Cholecysto-Cholangiography (PTCC) is a minimally invasive study which can be utilized in the diagnostic work-up of these patients. This study's purpose is to describe the experience with PTCC in neonates, the imaging findings encountered, and the abnormal patterns which warrant further investigation. METHODS A 16-year single-center retrospective study of patients with persistent neonatal cholestasis (suspected BA) undergoing PTCC. Patient demographics, laboratory values, PTCC images, pathology and surgical reports were reviewed. RESULTS 73 patients underwent PTCC (68% male, mean age 8.7 weeks, mean weight 4.0 Kg). The majority of studies were normal (55%). Abnormal patterns were identified in 33 cases, 79% were diagnosed with BA and 12% with Alagille syndrome. Non-opacification of the common hepatic duct with a narrowed common bile duct (42%) and isolated small gallbladder (38%) were the most common patterns in BA. CONCLUSION PTCC is a minimally invasive study in the diagnostic work-up of infants presenting with conjugated hyperbilirubinemia (suspected BA). Further invasive investigations or surgery can be avoided when results are normal.
Collapse
|
|
16
|
Selective enlargement of left lateral segment liver volume as a potential diagnostic predictor for biliary atresia. Pediatr Surg Int 2022; 38:1815-1820. [PMID: 36109363 DOI: 10.1007/s00383-022-05227-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2022] [Indexed: 10/14/2022]
Abstract
PURPOSE To determine an early diagnostic indicator of biliary atresia (BA), we focused on morphological left-right differences of BA livers. METHODS Of 74 infants with suspected BA at our hospital in the last 12 years, 25 met the conditions for investigation: 15 infants with BA (BA group) and 10 with other pathologies (non-BA group). CT volumetry of the liver in each patient was performed using a 3D image analysis system. Patient characteristics, blood data, and proportion of the left lateral segment to the total liver volume (LLS ratio) were compared between the two groups. RESULTS Among the patient characteristics and liver function tests, only γ-glutamyl transpeptidase (GGT) were significantly higher in the BA group (p < 0.001). The LLS ratio was 0.321 (0.227-0.382) in the BA group and 0.243 (0.193-0.289) in the non-BA group (p = 0.01). The summary cut-off, area under the curve, sensitivity, and specificity were 0.322, 0.813, 53.3, and 100% for the LLS ratio and 94.26, 0.95, 86.7, and 100% for the GGT × LLS ratio, respectively. CONCLUSIONS The LLS ratio is highly specific and may be an early diagnostic predictor of BA. Moreover, this segmental LLS enlargement may be associated with the etiology of BA.
Collapse
|
|
17
|
Zhang R, Huang J, Shan J, Chen Y, Xia H. Peripheral blood CD177 + cells as an early diagnostic marker for biliary atresia: A prospective multicentre study in pediatric patients with cholestasis. J Hepatol 2022; 77:1714-1716. [PMID: 35995126 DOI: 10.1016/j.jhep.2022.08.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/10/2022] [Accepted: 08/11/2022] [Indexed: 12/04/2022]
Affiliation(s)
- Ruizhong Zhang
- Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China; Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Junyu Huang
- Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China
| | - Jiarou Shan
- Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China
| | - Yan Chen
- Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China; Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
| | - Huimin Xia
- Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
| |
Collapse
|
|
18
|
Value of gallbladder length-to-width ratio for diagnosis of biliary atresia by correlation with age. Updates Surg 2022:10.1007/s13304-022-01427-x. [PMID: 36418718 DOI: 10.1007/s13304-022-01427-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/14/2022] [Indexed: 11/25/2022]
|
|
19
|
Weng Z, Zhou W, Wu Q, Ma H, Fang Y, Dang T, Ling W, Liu M, Zhou L. Gamma-Glutamyl Transferase Combined With Conventional Ultrasound Features in Diagnosing Biliary Atresia: A Two-Center Retrospective Analysis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:2805-2817. [PMID: 35229893 DOI: 10.1002/jum.15968] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/09/2022] [Accepted: 02/12/2022] [Indexed: 06/14/2023]
Abstract
OBJECTIVES To develop and validate a biliary atresia (BA) diagnostic score based on serum gamma-glutamyl transferase (GGT) levels and conventional ultrasound features for discriminating BA in patients with jaundice from two centers. METHODS A total of 958 patients from one hospital were classified as the derivation cohort, and 725 patients from another hospital were classified as the validation cohort. The optimal GGT cutoff value for diagnosing BA was calculated in the derivation cohort and subsequently verified in the validation cohort. Gallbladder abnormalities and the triangular cord (TC) sign were evaluated in all patients. A BA diagnostic score was developed for diagnosing BA using the GGT levels, gallbladder abnormalities and the TC sign based on the data from the derivation cohort followed by external validation. RESULTS Based on the optimal cutoff value 350.0 U/L, GGT yielded a sensitivity of 59.3% and specificity of 85.4% in diagnosing BA. The area under the receiver operating characteristic curve (AUC 0.724) was inferior to that of the gallbladder (AUC 0.911, P < .001) and comparable to that of the TC sign (AUC 0.771, P = .128). The combination of GGT and ultrasound diagnosis could help to reduce the misdiagnosis of 9 infants with BA. The BA diagnostic score yielded a sensitivity of 93.3% and specificity of 95.0% with the highest AUC in this study (0.941). CONCLUSIONS GGT can add diagnostic value to ultrasound examination when diagnosing BA. The BA diagnostic score based on GGT, gallbladder abnormalities and the TC sign shows satisfactory discrimination abilities in BA.
Collapse
Affiliation(s)
- Zongjie Weng
- Department of Medical Ultrasonics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Wenying Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Qiumei Wu
- Department of Medical Ultrasonics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Hong Ma
- Department of Pathology, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Yifan Fang
- Department of Pediatric Surgery, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Tingting Dang
- Department of Medical Ultrasonics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Wen Ling
- Department of Medical Ultrasonics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Min Liu
- Department of Medical Ultrasonics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou City, China
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| |
Collapse
|
|
20
|
Salvi PS, Fawaz R, Cowles RA. Comparing Serum Matrix Metalloproteinase-7 in Parenteral Nutrition-Associated Liver Disease and Biliary Atresia. J Pediatr 2022; 249:97-100. [PMID: 35714967 DOI: 10.1016/j.jpeds.2022.06.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/17/2022] [Accepted: 06/09/2022] [Indexed: 11/26/2022]
Abstract
In this cross-sectional study, serum matrix metalloproteinase-7 levels were significantly lower in infants with jaundice and parenteral nutrition-associated liver disease compared with those with confirmed biliary atresia. Serum metalloproteinase-7 may aid in excluding biliary atresia and thus may minimize invasive testing in infants with a history of parenteral nutrition.
Collapse
Affiliation(s)
- Pooja S Salvi
- Department of Surgery, Division of Pediatric Surgery, Yale School of Medicine, New Haven, CT
| | - Rima Fawaz
- Section of Pediatric Gastroenterology and Hepatology, Yale-New Haven Hospital, New Haven, CT
| | - Robert A Cowles
- Department of Surgery, Division of Pediatric Surgery, Yale School of Medicine, New Haven, CT.
| |
Collapse
|
|
21
|
Bai Y, Wang P, Qi Y, Li Y, Liu W, Gao L, Jiao H, An Y, Gong Y. Diagnostic value of HA, PC-III, IV-C, and LN in infants with congenital biliary atresia. Medicine (Baltimore) 2022; 101:e29752. [PMID: 35960122 PMCID: PMC9371546 DOI: 10.1097/md.0000000000029752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Hyaluronic acid (HA), type III procollagen III (PC-III), type IV collagen IV (IV-C), and laminin (LN) have certain diagnostic value for hepatobiliary diseases. No published studies have compared the diagnostic accuracy of these 4 indicators for the diagnosis of congenital biliary atresia (CBA) in infants. This study aimed to investigate the diagnostic value of HA, PC-III, IV-C, and LN in infants with CBA. From January 2017 to December 2020, 185 infants with nonphysiological jaundice in the Second Department of General Surgery at the Children's Hospital of Hebei were enrolled in this study. Forty-six infants with CBA (CBA group) and 139 infants without CBA (noncongenital biliary atresia group) were diagnosed using ultrasonography, magnetic resonance imaging, intraoperative exploration, and intraoperative cholangiography. The levels of HA, PC-III, IV-C, and LN in the 2 groups were statistically analyzed. The diagnostic accuracy was determined using receiver operating characteristic curves and by calculating the area under the curve. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors. Compared to the noncongenital biliary atresia group, the levels of HA, PC-III, IV-C, and LN were significantly increased in the CBA group (P <.05). The receiver operating characteristic analysis showed the optimal cutoff values for HA, PC-III, IV-C, and LN were 162.7, 42.5, 199.7, and 101.2 ng/mL, and the area under the curves were 0.892, 0.762, 0.804, and 0.768, respectively. The sensitivity values for the diagnosis of CBA were 76.82%, 71.61%, 70.32%, and 72.28%, and the specificity values for the diagnosis of biliary atresia were 70.22%, 70.44%, 66.34%, and 68.71%, respectively. In the multivariate model, HA ≥162.7 ng/mL (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 3.15-8.37), PC-III ≥42.5 ng/mL (OR = 4.61, 95% CI: 2.54-7.16), IV-C ≥199.7 ng/mL (OR = 5.02, 95% CI: 2.98-7.64), and LN ≥101.2 ng/mL (OR = 6.25, 95% CI: 2.41-10.07) remained associated with the occurrence of CBA. HA, PC-III, IV-C, and LN have high accuracy for the diagnosis of CBA in infants, and these factors are potential diagnostic biomarkers for CBA.
Collapse
Affiliation(s)
- Yukun Bai
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Ping Wang
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Yanwei Qi
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Yang Li
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Weidong Liu
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Lei Gao
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Hanliang Jiao
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Yanxiao An
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
| | - Yingxin Gong
- The Second Department of General Surgery, Children’s Hospital of Hebei, Shijiazhuang City, Hebei Province, China
- *Correspondence: Ying-Xin Gong, The Second Department of General Surgery, Children’s Hospital of Hebei, No 133 Jianhua South Street, Yuhua District, Shijiazhuang City, Hebei Province 050030, China (e-mail: )
| |
Collapse
|
|
22
|
Sun Y, Dai S, Shen Z, Yang Y, Hong S, Dong R, Sun S, Zheng S, Lynn HS, Chen G. Gamma-glutamyl transpeptidase has different efficacy on biliary atresia diagnosis in different hospital patient groups: an application of machine learning approach. Pediatr Surg Int 2022; 38:1131-1141. [PMID: 35713702 DOI: 10.1007/s00383-022-05148-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/24/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. METHODS Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children's Hospital of Fudan University were enrolled, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups. RESULTS Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC = 0.855) for patients with hemoglobin (HGB) ≤ 105 g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB > 105 g/L (AUC = 0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p = 0.002) prediction performance. CONCLUSIONS This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT.
Collapse
Affiliation(s)
- YuQi Sun
- Department of Biostatistics, Key Laboratory on Public Health, Safety of the Ministry of Education, School of Public Health, Fudan University, 130 Dong'an Rd, Shanghai, 200032, China
| | - ShuYang Dai
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Zhen Shen
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Yifan Yang
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Shangzhi Hong
- Department of Statistics and Programming, Shanghai Shengdi Pharmaceutical Company Limited, Jiangsu Hengrui Medicine Company Limited, Shanghai, 200120, China
| | - Rui Dong
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Song Sun
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China
| | - Shan Zheng
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
| | - Henry S Lynn
- Department of Biostatistics, Key Laboratory on Public Health, Safety of the Ministry of Education, School of Public Health, Fudan University, 130 Dong'an Rd, Shanghai, 200032, China.
| | - Gong Chen
- Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
| |
Collapse
|
|
23
|
Liu Y, Xu R, Wu D, Wang K, Tu W, Peng C, Chen Y. Development and validation of a novel nomogram and risk score for biliary atresia in patients with cholestasis. Dig Liver Dis 2022; 54:1109-1116. [PMID: 34654678 DOI: 10.1016/j.dld.2021.09.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 09/22/2021] [Accepted: 09/23/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Timely discriminating biliary atresia (BA) from other causes of cholestasis is important but challenging. AIMS To develop a useful diagnostic nomogram and a simplified scoring system to diagnosing BA. STUDY DESIGN All medical records of the patients who were consecutively admitted to our institution with cholestasis from March 2016 to December 2020 were retrospectively searched. The patients were allocated to the derivation cohort (n = 343) and the validation cohort (n = 246). Multivariable logistic regression models were used to construct the nomogram. The nomogram was validated in both cohorts. The simplified risk score was derived from the nomogram. RESULTS The nomogram was constructed based on presence of clay stool, gallbladder length, gallbladder emptying index, shear wave elastography value, and gamma-glutamyl transferase level. This model showed good calibration and discrimination ability, with the C-index of 0.968 (95% CI: 0.951-0.984). The discriminating ability is most prominent in the 61-90 days group, with AUC of 0.982 (95% CI: 0.955-1.000). The simplified risk score identified most patients with very high or low risk of BA, and was capable of exempting 64.3% non-BA patients from intraoperative cholangiogram procedure. CONCLUSIONS This novel diagnostic nomogram had good discrimination and calibration abilities. The simplified scoring system showed significant clinical utility.
Collapse
Affiliation(s)
- Yakun Liu
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi St, Beijing 100045, China
| | - Ruone Xu
- Shanghai Medical College, Fudan University, No. 138 Yixueyuan St, Shanghai 200032, China
| | - Dongyang Wu
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi St, Beijing 100045, China
| | - Kai Wang
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi St, Beijing 100045, China
| | - Wenjun Tu
- Key Lab of Cerebral Microcirculation in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, No. 619 Changcheng St, Taian, Shandong 271000, China
| | - Chunhui Peng
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi St, Beijing 100045, China.
| | - Yajun Chen
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi St, Beijing 100045, China.
| |
Collapse
|
|
24
|
Antala S, Taylor SA. Biliary Atresia in Children: Update on Disease Mechanism, Therapies, and Patient Outcomes. Clin Liver Dis 2022; 26:341-354. [PMID: 35868678 PMCID: PMC9309872 DOI: 10.1016/j.cld.2022.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Biliary atresia is a rare disease but remains the most common indication for pediatric liver transplantation as there are no effective medical therapies to slow progression after diagnosis. Variable contribution of genetic, immune, and environmental factors contributes to disease heterogeneity among patients with biliary atresia. Developing a deeper understanding of the disease mechanism will help to develop targeted medical therapies and improve patient outcomes.
Collapse
Affiliation(s)
- Swati Antala
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA
| | - Sarah A. Taylor
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA
| |
Collapse
|
|
25
|
He L, Chung PHY, Lui VCH, Tang CSM, Tam PKH. Current Understanding in the Clinical Characteristics and Molecular Mechanisms in Different Subtypes of Biliary Atresia. Int J Mol Sci 2022; 23:ijms23094841. [PMID: 35563229 PMCID: PMC9103665 DOI: 10.3390/ijms23094841] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/23/2022] [Accepted: 04/24/2022] [Indexed: 02/01/2023] Open
Abstract
Biliary atresia is a severe obliterative cholangiopathy in early infancy that is by far the most common cause of surgical jaundice and the most common indicator for liver transplantation in children. With the advanced knowledge gained from different clinical trials and the development of research models, a more precise clinical classification of BA (i.e., isolated BA (IBA), cystic BA (CBA), syndromic BA (SBA), and cytomegalovirus-associated BA (CMVBA)) is proposed. Different BA subtypes have similar yet distinguishable clinical manifestations. The clinical and etiological heterogeneity leads to dramatically different prognoses; hence, treatment needs to be specific. In this study, we reviewed the clinical characteristics of different BA subtypes and revealed the molecular mechanisms of their developmental contributors. We aimed to highlight the differences among these various subtypes of BA which ultimately contribute to the development of a specific management protocol for each subtype.
Collapse
Affiliation(s)
- Lin He
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China;
| | - Patrick Ho Yu Chung
- Division of Paediatric Surgery, Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (V.C.H.L.); (C.S.M.T.); (P.K.H.T.)
- Correspondence: ; Tel.: +852-22554850; Fax: +852-28173155
| | - Vincent Chi Hang Lui
- Division of Paediatric Surgery, Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (V.C.H.L.); (C.S.M.T.); (P.K.H.T.)
| | - Clara Sze Man Tang
- Division of Paediatric Surgery, Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (V.C.H.L.); (C.S.M.T.); (P.K.H.T.)
| | - Paul Kwong Hang Tam
- Division of Paediatric Surgery, Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (V.C.H.L.); (C.S.M.T.); (P.K.H.T.)
- Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China
| |
Collapse
|
|
26
|
Liu Y, Peng C, Wang K, Wu D, Yan J, Tu W, Chen Y. The utility of shear wave elastography and serum biomarkers for diagnosing biliary atresia and predicting clinical outcomes. Eur J Pediatr 2022; 181:73-82. [PMID: 34191129 DOI: 10.1007/s00431-021-04176-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 06/20/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022]
Abstract
To investigate the utility of liver stiffness measurement by shear wave elastography (SWE) and several commonly used biomarkers in differentiating biliary atresia (BA) from other causes of cholestasis (non-BA) patients within 45 days and in predicting the postoperative prognosis. A consecutive series of medical records of patients presenting with cholestasis within 45 days in our institution between February 2016 and December 2020 was collected. The BA diagnosis was confirmed by intraoperative cholangiography (IOC). Other causes of cholestasis were confirmed by IOC, liver biopsy, genetic analysis, or recovery after conservative treatment. Preoperative and postoperative data were analyzed. A total of 156 patients were included, consisting of BA (n = 83) and non-BA (n = 73) cases. SWE and serum gamma-glutamyl transferase (GGT) showed better discriminative utility. The optimal cutoff values for SWE and GGT were > 7.10 kPa and > 195.4 U/L, with AUC of 0.82 (95% CI, 0.76-0.89; p < 0.0001) and 0.87 (95% CI, 0.82-0.93; p < 0.0001), respectively. Subgroup analysis showed the increased discriminative performance of SWE with age. Multivariable logistic regression analysis showed better diagnostic performance for SWE (adjusted OR, 35.03; 95% CI, 7.12-172.50) and GGT (adjusted OR, 24.70; 95% CI, 6.55-93.18) after adjusting for other confounders. The 30-day postoperative to preoperative serum direct bilirubin (DB) level, DB (post-30:pre), of > 0.3 showed the best predictive value for the need of liver transplantation, with HR of 6.15 (95% CI 1.95-19.38, P = 0.042).Conclusion: Serum GGT level and liver stiffness measurement by SWE showed the best discriminative utility. The diagnostic performance of SWE increased with age. A DB (post-30:pre) value > 0.3 was associated with the need for liver transplantation in later life. What is Known: • Liver stiffness measurement by shear wave elastography (SWE) could help discriminate biliary atresia (BA) from other causes of cholestasis, with sensitivity of 70-90%. • The postoperative total bilirubin less than 2 mg/dL within the first 3 months was a predictor of transplant-free survival. What is New: • The diagnostic performance of liver stiffness measurement by SWE increased with age. • The 30-day postoperative direct bilirubin (DB) level to preoperative DB level, DB (post-30:pre), is a predictor for short-term clinical outcomes.
Collapse
Affiliation(s)
- Yakun Liu
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China
| | - Chunhui Peng
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China
| | - Kai Wang
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China
| | - Dongyang Wu
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China
| | - Jun Yan
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China
| | - Wenjun Tu
- Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, No. 238 Baidi St, Tianjin, 300192, China.
- Key Lab of Cerebral Microcirculation in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, No. 619 Changcheng St, Taian, 271000, Shandong, China.
| | - Yajun Chen
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, No. 56 Nanlishi St, Beijing, 100045, China.
| |
Collapse
|
|
27
|
Zhao J, Xu X, Gou Q, Zheng Q, Ge L, Chen L, Zhang C, Ma H, Lin S, Hu X, Zhan J. TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia. Front Pediatr 2022; 10:901888. [PMID: 35928681 PMCID: PMC9345500 DOI: 10.3389/fped.2022.901888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/20/2022] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE Biliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA. METHODS A total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves. RESULTS LECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; r s = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90-1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2. CONCLUSION LECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.
Collapse
Affiliation(s)
- Jinfeng Zhao
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Xiaodan Xu
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Qingyun Gou
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Qipeng Zheng
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Liang Ge
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Lingzhi Chen
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Cong Zhang
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Hui Ma
- Department of Laboratory Medicine, Tianjin Children's Hospital, Tianjin, China
| | - Shuxiang Lin
- Department of Pediatric Research Institute, Tianjin Children's Hospital, Tianjin, China
| | - Xiaoli Hu
- Department of Pathology, Tianjin Children's Hospital, Tianjin, China
| | - Jianghua Zhan
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| |
Collapse
|
|
28
|
Lyu H, Ye Y, Lui VCH, Wu W, Chung PHY, Wong KKY, Li HW, Wong MS, Tam PKH, Wang B. Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia. Front Surg 2022; 9:931637. [PMID: 36132201 PMCID: PMC9483031 DOI: 10.3389/fsurg.2022.931637] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 08/08/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown. METHOD Plasma samples of 11 BA and 24 controls were collected for liver function test, Aβ40 and Aβ42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann-Whitney U test was performed to assess differences between groups. Correlation between Aβ42/Aβ40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of Aβ42/Aβ40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aβ42/Aβ40 combined with other hepatic function parameters. RESULTS Plasma Aβ42/Aβ40 was elevated in BA patients. Aβ42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson's correlation = 0.349), while there was no correlation for Aβ40 with hepatic functions. Aβ42/Aβ40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson's correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson's correlation = 0.337). Aβ42/Aβ40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552-0.941), p < 0.05]. Diagnostic powers of Aβ42/Aβ40 together with hepatic function parameters for cholestasis were markedly improved compared to any indicator alone. Neither Aβ42/Aβ40 nor hepatic function parameters displayed sufficient power in discriminating BA from choledochal cysts (CC); however, combinations of Aβ42/Aβ40 + GGT along with any other hepatic function parameters could differentiate BA from CC-cholestasis (AUC = 1.000, p < 0.05) with a cut-off value as 0.02371, -0.28387, -0.34583, 0.06224, 0.01040, 0.06808, and 0.05898, respectively. CONCLUSION Aβ42/Aβ40 is a good indicator for cholestasis, but alone is insufficient for a distinction of BA from non-BA. However, Aβ42/Aβ40 combined with GGT and one other hepatic function parameter displayed a high predictive power as a screening test for jaundiced neonates who are more likely to be BA, enabling them to early intraoperative cholangiography for BA confirmation and KPE to improve surgical outcomes. However, a multi-centers validation is needed before introduction into daily clinical practice.
Collapse
Affiliation(s)
- Hongyu Lyu
- Graduate School, China Medical University, Shenyang, China
| | - Yongqin Ye
- Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, China
- Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau SAR, China
| | - Vincent Chi Hang Lui
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
- Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Weifang Wu
- Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, China
- Medical College, Shantou University Medical College, Shantou, China
| | - Patrick Ho Yu Chung
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
- Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Kenneth Kak Yuen Wong
- Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
- Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Hung-Wing Li
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Man Shing Wong
- Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China
| | - Paul Kwong Hang Tam
- Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau SAR, China
- Correspondence: Paul Kwong Hang Tam Bin Wang
| | - Bin Wang
- Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, China
- Correspondence: Paul Kwong Hang Tam Bin Wang
| |
Collapse
|
|
29
|
Sun S, Zheng S, Shen C, Dong R, Dong K, Jiang J, Yang Y, Chen G. Low gamma-glutamyl transpeptidase levels at presentation are associated with severity of liver illness and poor outcome in biliary atresia. Front Pediatr 2022; 10:956732. [PMID: 36210948 PMCID: PMC9537731 DOI: 10.3389/fped.2022.956732] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE To investigate the clinical features and prognosis of biliary atresia (BA) with normal or minimally elevated gamma-glutamyl transpeptidase (GGT). METHODS The clinical data of patients with BA in our hospital between 2012 and 2017 were retrospectively studied. The patients were divided into a low-GGT group (GGT ≤ 300 IU/L) and a high-GGT group (GGT > 300 IU/L) according to the preoperative GGT level. The perioperative clinical parameters, the postoperative jaundice clearance within 6 months, and the 2-year native liver survival were compared among the groups. RESULTS A total of 1,998 children were included in this study, namely, 496 in the low-GGT group and 1,502 in the high-GGT group. The ages and weights at the surgery in the low-GGT group were significantly lower than those in the high-GGT group (64.71 ± 21.35 vs. 68.64 ± 22.42 days, P = 0.001; 4.67 ± 1.03 vs. 4.89 ± 0.98 kg, P < 0.001). The levels of serum ALP, ALT, and AST in the low-GGT group were significantly higher than those in the high-GGT group before and 2 weeks after the surgery (ALP: 647.52 ± 244.10 vs. 594.14 ± 228.33 U/L, P < 0.001; ALT: 119.62 ± 97.14 vs. 96.01 ± 66.28 U/L, P < 0.001; AST: 218.00 ± 173.82 vs. 160.71 ± 96.32 U/L; P < 0.001). The INR of the low-GGT group was higher than that of the high-GGT group (1.05 ± 0.34 vs. 0.98 ± 0.20, P < 0.001), while FIB was lower than the high-GGT group (2.54 ± 0.67 vs. 2.73 ± 1.44 g/L; P = 0.006). The decreasing amplitude of TB and DB within 2 weeks after surgery in the low-GGT group was smaller than those in the high-GGT group (TB: 51.62 ± 71.22 vs. 61.67 ± 53.99 μmol/L, P = 0.003; DB: 33.22 ± 35.57 vs. 40.20 ± 35.93 μmol/L, P < 0.001). The jaundice clearance rate in the low-GGT group was significantly lower than that in the high-GGT group at 1, 3, and 6 months after surgery (17.70 vs. 26.05%; 35.17 vs. 48.58%; 38.62 vs. 54.64%, P < 0.001). In addition, the 2-year native liver survival rate in the low-GGT group was significantly lower than that of the high-GGT group (52.5 vs. 66.3%, P < 0.001 HR 1.80, 95% CI 1.38-2.33). CONCLUSION Compared to patients with high GGT, patients with normal or minimally elevated pre-operative GGT in BA were found to have poorer pre-operative liver function parameters, and post-operatively had lower jaundice clearance rates and worse 2-year native liver survival. This suggests a lower GGT at presentation in biliary atresia could be a sign of more severe liver injury.
Collapse
Affiliation(s)
- Song Sun
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Shan Zheng
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Chun Shen
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Rui Dong
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Kuiran Dong
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Jingying Jiang
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Yifan Yang
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| | - Gong Chen
- Surgical Department, Children's Hospital of Fudan University, Shanghai, China
| |
Collapse
|
|
30
|
Chen YT, Gao MJ, Zheng ZB, Huang L, Du Q, Zhu DW, Liu YM, Jin Z. Comparative analysis of cystic biliary atresia and choledochal cysts. Front Pediatr 2022; 10:947876. [PMID: 36090570 PMCID: PMC9448952 DOI: 10.3389/fped.2022.947876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 07/27/2022] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment. METHOD The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA (n = 12) and CC (n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups. RESULTS The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group (P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size. CONCLUSION For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants.
Collapse
Affiliation(s)
- Yu-Tong Chen
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Ming-Juan Gao
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Ze-Bing Zheng
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Lu Huang
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Qing Du
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Dai-Wei Zhu
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Yuan-Mei Liu
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| | - Zhu Jin
- Department of Pediatric Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.,Department of Pediatric Surgery, Guizhou Children's Hospital, Zunyi, China
| |
Collapse
|
|
31
|
Mohamadien NRA, Makboul R, Galal SM, Mostafa NM. Role of hepatobiliary scintigraphy with different semi-quantitative parameters along with histopathological scoring in differentiating biliary atresia from neonatal hepatitis. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00482-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Abstract
Background
Biliary atresia (BA) and neonatal hepatitis (NH) are the two major causes of neonatal cholestasis (NC). However, both conditions had entirely different therapeutic schedule and prognosis. Considering BA as a surgical emergency, it is pretty important to accurately differentiate the two entities. The aim of the study is to evaluate the diagnostic utility of hepatobiliary scintigraphy (HBS) using a semi-quantitative technique as well as 15-point histopathological scoring system in differentiating BA from NH.
Results
The sensitivity, specificity, and overall accuracy of HBS in the diagnosis of BA was 90.5%, 80%, and 83.6%, respectively. The median values of kidney-liver ratio (KLR), intestinal-liver ratio (ILR), and background-liver ratio (BLR) were significantly higher in patients with BA, while that of the liver-kidney ratio (LKR) was significantly lower in cases with BA. Moreover, KLR had the largest area under curve (AUC); advocates it to be the best of the semi-quantitative parameters that can predicts BA. Histopathological scoring using a cutoff point ≥ 7 was helpful in discriminating BA from NH with 85.7% sensitivity, 95% specificity and 91.8% accuracy.
Conclusions
HBS is a non-invasive diagnostic tool frequently used in diagnosis of BA, yet it has a relatively low specificity. To overcome this challenge, we kindly recommend the use of semi-quantitative parameters that could possibly improve the accuracy of HBS for diagnosing BA. Additionally, the use of 15-point scoring for liver biopsy was useful.
Collapse
|
|
32
|
Wang G, Zhang N, Zhang X, Zhou W, Xie X, Zhou L. Ultrasound characteristics combined with gamma-glutamyl transpeptidase for diagnosis of biliary atresia in infants less than 30 days. Pediatr Surg Int 2021; 37:1175-1182. [PMID: 34008061 DOI: 10.1007/s00383-021-04923-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/05/2021] [Indexed: 01/09/2023]
Abstract
PURPOSE To retrospectively assess the diagnostic performance of grey-scale ultrasound (US) characteristics and gamma-glutamyl transpeptidase (GGT) alone or combined in distinguishing biliary atresia (BA) from other cholestasis diseases in infants younger than 30 days. MATERIALS AND METHODS Between January 2012 and October 2020, the demographic characteristics, laboratory results and US characteristics of 35 BA and 52 non-BA infants younger than 30 days were retrospectively evaluated. Areas under the receiver operating characteristic curves (AUCs) were used to estimate the probability of predicting BA, which were compared by DeLong test. RESULTS The diagnostic performance of gallbladder classification in identifying BA was higher than that of fibrotic cord thickness (AUC 0.900 vs. 0.771, P = 0.03). With the cutoff level of 188 IU/L, serum GGT had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 77.1%, 69.2%, 62.8%, and 81.8%, respectively. Combined with gallbladder classification and GGT, the sensitivity, specificity, PPV, NPV and accuracy were 100.0%, 63.5%, 64.8%, 100.0% and 78.2%. CONCLUSIONS Gallbladder classification was more valuable than fibrotic cord thickness in the diagnosis of BA among infants less than 30 days. Combined with gallbladder classification and GGT, the sensitivity for the diagnosis of BA can reach 100.0%.
Collapse
Affiliation(s)
- Guotao Wang
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Nan Zhang
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Xiaoer Zhang
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Wenying Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China.
| |
Collapse
|
|
33
|
Practical approach for the diagnosis of biliary atresia on imaging, part 2: magnetic resonance cholecystopancreatography, hepatobiliary scintigraphy, percutaneous cholecysto-cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous liver biopsy, risk scores and decisional flowchart. Pediatr Radiol 2021; 51:1545-1554. [PMID: 33974103 DOI: 10.1007/s00247-021-05034-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/23/2020] [Accepted: 02/21/2021] [Indexed: 12/11/2022]
Abstract
We aim to present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses to biliary cirrhosis, end-stage liver failure and death within the first years of life. Differentiating biliary atresia from other nonsurgical causes of neonatal cholestasis is difficult as there is no single method for diagnosing biliary atresia and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. In this second part, we discuss the roles of magnetic resonance (MR) cholecystopancreatography, hepatobiliary scintigraphy, percutaneous biopsy and percutaneous cholecysto-cholangiography. Among imaging techniques, ultrasound (US) signs have a high specificity, although a normal US examination does not rule out biliary atresia. Other imaging techniques with direct opacification of the biliary tree combined with percutaneous liver biopsy have roles in equivocal cases. MR cholecystopancreatography and hepatobiliary scintigraphy are not useful for the diagnosis of biliary atresia. We propose a decisional flowchart for biliary atresia diagnosis based on US signs, including elastography, percutaneous cholecysto-cholangiography or endoscopic retrograde cholangiopancreatography and liver biopsy.
Collapse
|
|
34
|
Galina P, Alexopoulou E, Mentessidou A, Mirilas P, Zellos A, Lykopoulou L, Patereli A, Salpasaranis K, Kelekis NL, Zarifi M. Diagnostic accuracy of two-dimensional shear wave elastography in detecting hepatic fibrosis in children with autoimmune hepatitis, biliary atresia and other chronic liver diseases. Pediatr Radiol 2021; 51:1358-1368. [PMID: 33755748 DOI: 10.1007/s00247-020-04959-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/13/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although fibrosis is the main determinant of liver stiffness, other disease-related factors usually disregarded in studies on liver elastography, such as inflammation and cholestasis, may influence liver stiffness. OBJECTIVE To evaluate the accuracy of two-dimensional (2-D) shear wave elastography in assessing liver fibrosis in children with chronic liver disease by controlling for the confounding role of several disease- and patient-related factors. MATERIALS AND METHODS Three disease groups were studied: 1) various chronic liver diseases, 2) autoimmune hepatitis and 3) biliary atresia. The METAVIR (meta-analysis of histological data in viral hepatitis) score was used for fibrosis staging and grading of necroinflammatory activity. Multiple linear regression was used to evaluate the relationship between liver stiffness measurements and disease-related factors. The diagnostic accuracy of elastography for predicting fibrosis stages was assessed by calculating the area under the receiver operating characteristic curves. RESULTS The various chronic liver diseases group (n=32; 7.1±4.9 [mean±standard deviation] years) showed liver stiffness of 8.9±5.0 (mean±standard deviation) kPa, the autoimmune hepatitis group (n=33; 8.1±4.4 years) of 7.1±2.7 kPa, and the biliary atresia group (n=19; 0.2±0.1 years) of 19.7±15.2 kPa. Liver stiffness measurements differed across METAVIR fibrosis categories in all disease groups. The highest values were found in biliary atresia, at fibrosis stages ≥F2 (F2: 12.4±1.6 kPa, F3: 17.8±2 kPa, F4: 41.5±12.4 kPa). Liver stiffness was strongly associated only with fibrosis (P<0.0001) in various chronic liver diseases, but with necroinflammatory activity (P<0.0001) and fibrosis (P=0.002) in autoimmune hepatitis, and with age (P<0.0001), fibrosis (P<0.0001) and cholestasis (P=0.009) in biliary atresia. Optimal cutoffs for detecting advanced fibrosis (≥F3) were 16 kPa (area under curve: 0.98; sensitivity: 87.5%; specificity: 96.7%) in biliary atresia and 8.7 kPa (area under curve: 0.98; sensitivity: 93.8%; specificity: 96.1%) in other chronic liver diseases. CONCLUSION Two-dimensional shear wave elastography is reliable in assessing liver fibrosis in children with chronic liver diseases.
Collapse
Affiliation(s)
- Paraskevi Galina
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece. .,2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Efthymia Alexopoulou
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Mentessidou
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Petros Mirilas
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Aglaia Zellos
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Lilia Lykopoulou
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Amalia Patereli
- Department of Pathology, Aghia Sofia General Children's Hospital, Athens, Greece
| | | | - Nikolaos L Kelekis
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Zarifi
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece
| |
Collapse
|
|
35
|
He L, Ip DKM, Tam G, Lui VCH, Tam PKH, Chung PHY. Biomarkers for the diagnosis and post-Kasai portoenterostomy prognosis of biliary atresia: a systematic review and meta-analysis. Sci Rep 2021; 11:11692. [PMID: 34083585 PMCID: PMC8175424 DOI: 10.1038/s41598-021-91072-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 05/18/2021] [Indexed: 12/11/2022] Open
Abstract
To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and quality assessment were performed in duplicate. A total of 51 eligible studies were included in the systematic review, and data from 12 (4182 subjects) were extracted for meta-analysis regarding the following 2 domains: (1) serum matrix metallopeptidase-7 (MMP-7), interleukin33 (IL-33) and γ-glutamyl transferase (GGT) to differentiate BA from non-BA; (2) the aspartate aminotransferase to platelet ratio index (APRi) to predict post-KPE liver fibrosis/cirrhosis. The summary sensitivity, specificity and area under the curve (AUC) of MMP-7 for diagnosing BA were 96%, 91% and 0.9847, respectively, and those of GGT were 80%, 79% and 0.9645, respectively. The summary sensitivity and specificity of IL-33 for diagnosing BA were 77% and 85%, respectively. The summary sensitivity and specificity of APRi for predicting post-KPE liver fibrosis were 61% and 80%, respectively, and the summary sensitivity, specificity and AUC of APRi for predicting post-KPE cirrhosis were 78%, 83% and 0.8729, respectively. Moreover, good evidence was shown in investigations of serum IL-18 and IL-33 in distinguishing BA from healthy controls, serum IL-18 for prognosis of post-KPE persistent jaundice, and serum hyaluronic acid and MMP-7 for prognosis of post-KPE significant liver fibrosis. MMP-7, IL-33 and GGT are useful biomarkers to assist in the diagnosis of BA. APRi might be used to predict post-KPE significant liver fibrosis and cirrhosis. These noninvasive biomarkers can be integrated into the management protocol of BA.
Collapse
Affiliation(s)
- Lin He
- Department of Radiotherapy, Tangdu Hospital, Air Force Military Medical University, Xi'an, China
| | - Dennis Kai Ming Ip
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR
| | - Greta Tam
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR
| | - Vincent Chi Hang Lui
- Departmet of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR
| | - Paul Kwong Hang Tam
- Departmet of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR
| | - Patrick Ho Yu Chung
- Departmet of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR.
| |
Collapse
|
|
36
|
Liang J, Li H, Fu J, Liang Q, Liu T, Yang F, Zhang B, Bai X, Wen Z. A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:47-58. [PMID: 34029644 DOI: 10.1016/j.gastrohep.2021.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/01/2021] [Accepted: 02/08/2021] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. PATIENTS AND METHODS The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. RESULTS A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. CONCLUSIONS Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.
Collapse
Affiliation(s)
- Jiankun Liang
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Huixian Li
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Jie Fu
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Qifeng Liang
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Tao Liu
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Fengxia Yang
- Isolation Clinic, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Bingbing Zhang
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Xiaoling Bai
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Zhe Wen
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
| |
Collapse
|
|
37
|
Misra S, Majumdar K, Sakhuja P, Jain P, Singh L, Kumar P, Dubey AP. Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies. Pediatr Dev Pathol 2021; 24:103-115. [PMID: 33439108 DOI: 10.1177/1093526620983730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND AIMS Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. METHODS A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. RESULTS Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR)2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. CONCLUSIONS Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.
Collapse
Affiliation(s)
- Sunayana Misra
- Department of Pathology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India
| | - Kaushik Majumdar
- Department of Pathology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India
| | - Priyanka Jain
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Lavleen Singh
- Department of Pathology, Chacha Nehru Bal Chikitsalaya, New Delhi, India
| | - Praveen Kumar
- Department of Pediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India
| | - A P Dubey
- Department of Pediatrics, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India
| |
Collapse
|
|
38
|
Practical approach to imaging diagnosis of biliary atresia, Part 1: prenatal ultrasound and magnetic resonance imaging, and postnatal ultrasound. Pediatr Radiol 2021; 51:314-331. [PMID: 33201318 DOI: 10.1007/s00247-020-04840-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/16/2020] [Accepted: 09/07/2020] [Indexed: 12/27/2022]
Abstract
We present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses towards biliary cirrhosis, end-stage liver failure and death by age 3. Differentiation of biliary atresia from other nonsurgical causes of neonatal cholestasis is challenging because there is no single method for diagnosing biliary atresia, and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. Concerning imaging, our systematic literature review shows that ultrasonography is the main tool for pre- and neonatal diagnosis. Key prenatal features, when present, are non-visualisation of the gallbladder, cyst in the liver hilum, heterotaxy syndrome and irregular gallbladder walls. Postnatal imaging features have a very high specificity when present, but a variable sensitivity. Triangular cord sign and abnormal gallbladder have the highest sensitivity and specificity. The presence of macro- or microcyst or polysplenia syndrome is highly specific but less sensitive. The diameter of the hepatic artery and hepatic subcapsular flow are less reliable. When present in the context of acholic stools, dilated intrahepatic bile ducts rule out biliary atresia. Importantly, a normal US exam does not rule out biliary atresia. Signs of chronic hepatopathy and portal hypertension (portosystemic derivations such as patent ductus venosus, recanalised umbilical vein, splenomegaly and ascites) should be actively identified for - but are not specific for - biliary atresia.
Collapse
|
|
39
|
Ling DXH, Bolisetty S, Krishnan U. Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre. J Paediatr Child Health 2021; 57:87-95. [PMID: 32808395 DOI: 10.1111/jpc.15131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 07/17/2020] [Accepted: 07/26/2020] [Indexed: 11/27/2022]
Abstract
AIM To (i) review the aetiologies of neonatal cholestasis among term and preterm neonates at a single tertiary centre in Australia; (ii) identify clinical variables associated with biliary atresia (BA) and non-BA aetiology of neonatal cholestasis; (iii) investigate the utility of hepatobiliary scintigraphy in predicting BA among term and preterm neonates. METHODS A retrospective cohort study of neonates born and investigated for cholestasis at two co-located neonatal and children facilities from January 2013 to December 2017. RESULTS Of the 139 neonates with cholestasis, BA and intestinal-failure-associated liver-disease was the most common cause of neonatal cholestasis in term (18%) and preterm (66%) cohorts, respectively. Incidence of BA was higher in term (1:6) than preterm (1:50) neonates (OR 10.29; 95% CI 2.06-49.97, P = 0.0024). Higher birthweight, acholic stool, absent or abnormal gallbladder on ultrasound was significantly associated with BA while gestational age ≤32 weeks, total parenteral nutrition ≥14 days and low albumin were associated with non-BA aetiology of cholestasis. In diagnosing BA, non-draining hepatobiliary scintigraphy demonstrated a lower specificity (73% vs. 90%) and lower positive predictive value (25% vs. 78%) in preterm compared to term neonates. CONCLUSION Aetiology of cholestasis among preterm neonates differs from those in term neonates and currently existing diagnostic algorithm for neonatal cholestasis may need to be modified for preterm cohort, taking into account the prevalence for each aetiology, potential predictors and cost-efficiency.
Collapse
Affiliation(s)
- David X H Ling
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Srinivas Bolisetty
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,Department of Newborn Care, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Usha Krishnan
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,Department of Gastroenterology, Sydney Children Hospital, Sydney, New South Wales, Australia
| |
Collapse
|
|
40
|
Shen Q, Tan SS, Wang Z, Cai S, Pang W, Peng C, Chen Y. Combination of gamma-glutamyl transferase and liver stiffness measurement for biliary atresia screening at different ages: a retrospective analysis of 282 infants. BMC Pediatr 2020; 20:276. [PMID: 32498678 PMCID: PMC7271542 DOI: 10.1186/s12887-020-02172-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 05/27/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This study aims to explore the diagnostic accuracy of the combination of gamma-glutamyl transferase (GGT) and liver stiffness measurement (LSM) for biliary atresia (BA) screening at different ages. METHODS Our retrospective study involved 282 infants under the age of 120 days with jaundice who were admitted into Beijing Children's Hospital between January 2016 to December 2018. The GGT and LSM levels of infants were obtained. A parallel test was used, and ROC curve was created to obtain cutoff values of GGT and LSM for BA infants at different ages. RESULTS Of the 282 infants, 135 were diagnosed with BA and 147 were non-BA infants. In all age groups (A: ≤60 days; B: 61-90 days; C: 91-120 days), the LSM and GGT levels of the BA group were significantly higher than that of the non-BA group, P < 0.05. The cutoff value of GGT and LSM to diagnosis BA was 191.2 U/L, 213.2 U/L, 281.5 U/L and 7.5 kPa, 10.0 kPa, 11.0 kPa in groups A, B and C, respectively. The parallel test was used to determine a sensitivity of 97.3, 98.1 and 100% in group A, B and C when either GGT or LSM levels were met in BA infants. The sensitivities of parallel testing for group A and B were higher than LSM or GGT used alone. CONCLUSIONS Cutoff values of GGT and LSM to screen BA increased with age. Parallel testing of GGT and LSM in infants who are younger than 90 days old can decrease the rate of BA misdiagnosis.
Collapse
Affiliation(s)
- Qiulong Shen
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Sarah Siyin Tan
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Zengmeng Wang
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Siyu Cai
- Center for Clinical Epidemiology and Evidence-based Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Wenbo Pang
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Chunhui Peng
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China
| | - Yajun Chen
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi St, Xicheng District, Beijing, 100045, China.
| |
Collapse
|
|
41
|
Yoshii D, Inomata Y, Yamamoto H, Irie T, Kadohisa M, Okumura K, Isono K, Honda M, Hayashida S, Oya Y, Hibi T. The duodenal tube test is more specific than hepatobiliary scintigraphy for identifying bile excretion in the differential diagnosis of biliary atresia. Surg Today 2020; 50:1232-1239. [PMID: 32314016 DOI: 10.1007/s00595-020-02010-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 03/17/2020] [Indexed: 11/24/2022]
Abstract
PURPOSE Confirmation of bile excretion into the gastrointestinal tract is important to exclude biliary atresia (BA). We compared the duodenal tube test (DTT) with hepatobiliary scintigraphy (HS) for their efficiency in detecting bile secretion. METHODS The subjects of this retrospective study were 47 infants who underwent both DTT and HS to diagnose or exclude BA between January 2000 and March 2018. RESULTS BA was diagnosed in 32 of the 47 patients, and 7 of the remaining 15 non-BA patients underwent intraoperative cholangiography. Among the various DTT parameters, the total bile acid in duodenal fluid (DF-TBA)/serum (S) gamma-glutamyl transferase (γGTP) ratio was found to be the most specific for BA, with sensitivity and specificity of 98.0-100%, respectively. One BA patient in whom cut off values were not met was a premature infant. The sensitivity and specificity of HS were 100-56.3%, respectively. The diagnostic accuracy of the DF-TBA/S-γGTP parameter was higher than that of HS (98.6% vs. 85.1%, respectively). CONCLUSIONS The DTT could be more a specific method than HS to detect bile excretion. Thus, the DTT should be incorporated into the multidisciplinary diagnostic approach for the differential diagnosis of BA to prevent unnecessary intraoperative cholangiography in patients who do not have BA.
Collapse
Affiliation(s)
- Daiki Yoshii
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| | - Yukihiro Inomata
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. .,Department of Pediatric Surgery and Transplantation, Kumamoto Rosai Hospital, 1670 Takeharamachi, Yatsushiro, Kumamoto, 866-8533, Japan.
| | - Hirotoshi Yamamoto
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.,Department of Pediatric Surgery, Kumamoto City Hospital, 4-1-60 Higashimachi, Higashi-ku, Kumamoto, Kumamoto, 862-8505, Japan
| | - Tomoaki Irie
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| | - Masashi Kadohisa
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| | - Kenji Okumura
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.,Department of Pediatric Surgery, Kumamoto City Hospital, 4-1-60 Higashimachi, Higashi-ku, Kumamoto, Kumamoto, 862-8505, Japan
| | - Kaori Isono
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| | - Masaki Honda
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| | - Shintaro Hayashida
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.,Department of Pediatric Surgery and Transplantation, Kumamoto Rosai Hospital, 1670 Takeharamachi, Yatsushiro, Kumamoto, 866-8533, Japan
| | - Yuki Oya
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.,Department of Pediatric Surgery and Transplantation, Kumamoto Rosai Hospital, 1670 Takeharamachi, Yatsushiro, Kumamoto, 866-8533, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan
| |
Collapse
|
|
42
|
Chen Y, Zhao D, Gu S, Li Y, Pan W, Zhang Y. Three-color risk stratification for improving the diagnostic accuracy for biliary atresia. Eur Radiol 2020; 30:3852-3861. [PMID: 32162000 DOI: 10.1007/s00330-020-06751-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 02/10/2020] [Accepted: 02/14/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVES It is challenging to early differentiate biliary atresia from other causes of cholestasis. We aimed to develop an algorithm with risk stratification to distinguish biliary atresia from infantile cholestasis. METHODS In this study, we enrolled infants with cholestasis into 2 subgroups from January 2010 to April 2019. A prospective cohort (subgroup 2) of 187 patients (107 with biliary atresia and 80 without biliary atresia) underwent acoustic radiation force impulse elastography. Stepwise regression was used to identify significant predictors of biliary atresia. A sequential algorithm with risk stratification was constructed. RESULTS Among 187 patients, shear wave speed > 1.35 m/s and presence of the triangular cord sign were considered high risk for biliary atresia (red), in which 73 of 78 patients (accuracy of 93.6%) with biliary atresia were identified. Afterwards, γ-GT, abnormal gallbladder, and clay stool were introduced into the algorithm and 55 intermediate-risk infants were identified (yellow) with a diagnostic accuracy of 60% for biliary atresia. Of the remaining 54 infants who were classified as low-risk patients (green), the accuracy for excluding biliary atresia was 98.1%. By applying a three-color risk stratification tool, 70.6% patients were identified as either high risk or low risk for biliary atresia (area under the curve, 0.983; sensitivity, 98.7%; specificity, 91.4%). We also estimated the risk of biliary atresia in different color groups, which was 94.7% (95%CI, 94.3-95.5%) in the red group and 7.2% (95%CI, 6.6-8.3%) in the green group. CONCLUSIONS Our simple noninvasive approach was able to identify biliary atresia with high accuracy. KEY POINTS • Five predictors, namely shear wave speed, triangle cord sign, γ-glutamyl transferase, abnormal gallbladder, and clay stool, were selected to identify biliary atresia in cholestasis. • Shear wave speed > 1.35 m/s and presence of the triangle cord sign were considered high-risk patients with a diagnostic accuracy of 93.6% for biliary atresia. • Risk for biliary atresia was high (red), intermediate (yellow), or low (green). In the red and green group, we achieved an extremely high diagnostic performance (area under the curve, 0.983; sensitivity, 98.7%; specificity, 91.4%).
Collapse
Affiliation(s)
- Yan Chen
- Department of Neonatology, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China
| | - Dongying Zhao
- Department of Neonatology, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China
| | - Shengli Gu
- Department of Ultrasound, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yahui Li
- Department of Neonatology, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China
| | - Weihua Pan
- Department of Pediatric Surgery, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China.
| | - Yongjun Zhang
- Department of Neonatology, Xinhua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092, China.
| |
Collapse
|
|
43
|
Normal Gamma Glutamyl Transferase Levels at Presentation Predict Poor Outcome in Biliary Atresia. J Pediatr Gastroenterol Nutr 2020; 70:350-355. [PMID: 31738295 DOI: 10.1097/mpg.0000000000002563] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVES Gamma-glutamyl transferase levels (GGT) are typically elevated in biliary atresia (BA), but normal GGT levels have been observed. This cohort of "normal GGT" BA has neither been described nor has the prognostic value of GGT level on outcomes in BA. We aimed to describe outcomes of a single-centre Australian cohort of infants with BA and assess the impact of GGT level at presentation on outcomes in BA. METHODS Infants diagnosed with BA between 1991 and 2017 were retrospectively analysed. Outcomes were defined as survival with native liver, liver transplantation (LT), and death. Patients were categorized into normal (<200I U/L) or high GGT groups based on a mean of 3 consecutive GGT values done before Kasai portoenterostomy (KPE). Baseline parameters, age at surgery, clearance of jaundice (COJ), and outcomes were compared between the 2 groups. RESULTS One hundred thirteen infants underwent KPE at median 61 (30-149) days. At a median follow-up of 14.2 (0.9-26.3) years, 35% (39/113) patients were surviving with native liver, 55% (62/113) underwent LT and 11% (12/113) died pretransplant. 12.3% (14/113) patients had normal GGT. Age at KPE and time to COJ were similar between normal and high GGT groups. Normal GGT group had shorter time from KPE to LT (11 vs 18 months, P = 0.02), underwent LT at a younger age (14 vs 20 months, P = 0.04), and had poorer transplant-free survival (P = 0.04) than high GGT group. CONCLUSIONS 12.3% of infants with BA had normal GGT levels at diagnosis. Low GGT levels at presentation in BA was associated with a poorer outcome.
Collapse
|
|
44
|
Liu J, Dai S, Chen G, Sun S, Jiang J, Zheng S, Zheng Y, Dong R. Diagnostic Value and Effectiveness of an Artificial Neural Network in Biliary Atresia. Front Pediatr 2020; 8:409. [PMID: 32903817 PMCID: PMC7438882 DOI: 10.3389/fped.2020.00409] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/15/2020] [Indexed: 12/12/2022] Open
Abstract
Objectives: Biliary atresia (BA) is a devastating pediatric liver disease. Early diagnosis is important for timely intervention and better prognosis. Using clinical parameters for non-invasive and efficient BA diagnosis, we aimed to establish an artificial neural network (ANN). Methods: A total of 2,384 obstructive jaundice patients from 2012 to 2017 and their 137 clinical parameters were screened for eligibility. A standard binary classification feed-forward ANN was employed. The network was trained and validated for accuracy. Gamma-glutamyl transpeptidase (GGT) level was used as an independent predictor and a comparison to assess the network effectiveness. Results: We included 46 parameters and 1,452 patients for ANN modeling. Total bilirubin, direct bilirubin, and GGT were the most significant indicators. The network consisted of an input layer, 3 hidden layers with 12 neurons each, and an output layer. The network showed good predictive property with a high area under curve (AUC) (0.967, sensitivity 97.2% and specificity 91.0%). Five-fold cross validation showed the mean accuracy for training data of 93.2% and for validation data of 88.6%. Conclusions: The high accuracy and efficiency demonstrated by the ANN model is promising in the noninvasive diagnosis of BA and could be considered as in a low-cost and independent expert diagnosis system.
Collapse
Affiliation(s)
- Jia Liu
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - ShuYang Dai
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - Gong Chen
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - Song Sun
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - JingYing Jiang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| | - YiJie Zheng
- Department of Medicine, Pulmonary Hospital Affiliated to Tongji University, Shanghai, China
| | - Rui Dong
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China
| |
Collapse
|
|
45
|
Fu HY, Zhao RQ, Bai GL, Yin CL, Yin RK, Li HH, Shi WN, Liu YL, Cheng LJ, Jia XY, Li GG, Zhao SG. [Value of serum gamma-glutamyl transpeptidase combined with direct bilirubin in the diagnosis of biliary atresia in infants]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21. [PMID: 31874659 PMCID: PMC7389014 DOI: 10.7499/j.issn.1008-8830.2019.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
OBJECTIVE To study the value of serum gamma-glutamyl transpeptidase (GGT) combined with direct bilirubin (DB) in the diagnosis of biliary atresia. METHODS A total of 667 infants with cholestasis who were hospitalized and treated from July 2010 to December 2018 were enrolled as subjects. According to the results of intraoperative cholangiography and follow-up, they were divided into biliary atresia group with 234 infants and cholestasis group with 433 infants. The two groups were compared in terms of age of onset, sex, and serum levels of total bilirubin (TB), DB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and GGT. A receiver operating characteristic (ROC) curve analysis was performed for indices with statistical significance, and the area under the ROC curve (AUC) and the optimal cut-off value for diagnosis were calculated. RESULTS The biliary atresia group had a significantly younger age of onset than the cholestasis group (P<0.001). There were no significant differences in sex, ALT, and AST between the two groups (P>0.05), while the biliary atresia group had significantly higher serum levels of TB, DB, TBA, and GGT than the cholestasis group (P<0.05). GGT combined with DB had the highest AUC of 0.892 (95% confidence interval: 0.868-0.916) in the diagnosis of biliary atresia. At the optimal cut-off values of 324.0 U/L for GGT and 115.1 μmmol/L for DB, GGT combined with DB had a sensitivity of 79.8% and a specificity of 83.2% in the diagnosis of biliary atresia. CONCLUSIONS GGT combined with DB has high sensitivity and specificity in the diagnosis of biliary atresia and can be used as an effective indicator for diagnosis of biliary atresia in infants.
Collapse
Affiliation(s)
- Hai-Yan Fu
- Department of Infectious and Digestive Diseases, Hebei Children's Hospital, Shijiazhuang 050031, China.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Jiang J, Wang J, Shen Z, Lu X, Chen G, Huang Y, Dong R, Zheng S. Serum MMP-7 in the Diagnosis of Biliary Atresia. Pediatrics 2019; 144:peds.2019-0902. [PMID: 31604829 DOI: 10.1542/peds.2019-0902] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/19/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. METHODS We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. RESULTS The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P < .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with γ glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P < .001). CONCLUSIONS MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.
Collapse
Affiliation(s)
- Jingying Jiang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Junfeng Wang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Zhen Shen
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Xuexin Lu
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Gong Chen
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Yanlei Huang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Rui Dong
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China
| |
Collapse
|
|
47
|
Tsuda N, Shiraishi S, Sakamoto F, Ogasawara K, Tomiguchi S, Yamashita Y. Tc-99m PMT scintigraphy in the diagnosis of pediatric biliary atresia. Jpn J Radiol 2019; 37:841-849. [PMID: 31571132 DOI: 10.1007/s11604-019-00882-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 09/17/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Hepatobiliary scintigraphy plays an important role in the differentiation of biliary atresia (BA) and non-BA. The usefulness of 99mTc-iminodiacetic acid (IDA) derivatives in BA diagnosis is reported in several papers. In contrast, there are no comprehensive data on differentiating BA from non-BA using 99mTc-N-pyridoxyl-5-methyl-tryptophan (PMT). Our objective was to evaluate the usefulness of 99mTc-PMT scintigraphy in the diagnosis of BA. MATERIALS AND METHODS 52 infants who received 99mTc-PMT scintigraphy for suspected BA were retrospectively evaluated. Preoperative cholangiograms or follow-ups were used as the gold standard for diagnosis of BA. We analyzed the utility of 99mTc-PMT scintigraphy, various clinical and investigational parameters in the diagnosis of BA. RESULTS The final diagnoses in this group were BA (67.3%) and non-BA (32.7%). 99mTc-PMT scintigraphy, stool color change, total bilirubin, direct bilirubin, aspartate aminotransferase (AST) and γ-glutamyl transferase (γ-GTP) led to distinguishing between BA and non-BA in univariate analysis. Subsequent multivariate logistic regression analysis indicated that 99mTc-PMT scintigraphy and γ-GTP were independent predictors of BA. The diagnostic accuracy of 99mTc-PMT scintigraphy was 94.2%. CONCLUSIONS 99mTc-PMT scintigraphy is more accurate in the diagnosis of BA than other conventional examinations. In addition, false positives of 99mTc-PMT scintigraphy could be reduced by combining γ-GTP level monitoring.
Collapse
Affiliation(s)
- Noriko Tsuda
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
| | - Shinya Shiraishi
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Fumi Sakamoto
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Koji Ogasawara
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Seiji Tomiguchi
- Department of Diagnostic Medical Imaging, School of Health Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasuyuki Yamashita
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| |
Collapse
|
|
48
|
Chen P, Zhong Z, Jiang H, Chen H, Lyu J, Zhou L. Th17-associated cytokines multiplex testing indicates the potential of macrophage inflammatory protein-3 alpha in the diagnosis of biliary atresia. Cytokine 2019; 116:21-26. [PMID: 30684914 DOI: 10.1016/j.cyto.2019.01.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/27/2018] [Accepted: 01/02/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Biliary atresia (BA) is a neonatal obliterative cholangiopathy with high prevalence in south China. Accurate identification of BA among infants with obstructive jaundice is still difficult by noninvasive diagnostic tools. Th17 cells have been reported closely related with the development of BA, which suggest that Th17-associated cytokines were potential biomarkers for the diagnosis of BA patients. METHODS In the training study, 76 infants who were divided into 2 groups, including BA group (n = 31) and non-BA jaundice group (n = 45). Clinical and routine laboratory data were collected from all subjects. Totally 25 Th17-associated cytokines were tested and compared between groups. The diagnostic value of each differential cytokine was evaluated by the area under the receiver operating characteristic curve (AUC). The best potential diagnostic biomarker was further validated in a cohort including 68 jaundice infants from our partnering institution in a blinded fashion. RESULTS Data from the training study showed that gamma-glutamyl transferase (GGT) and clay stool would be helpful in the identification of BA patients in jaundice subjects. Th17-associated cytokines assay indicated that IL-17F, IL-10, macrophage inflammatory protein-3alpha (MIP3a), IL-22, IL-13, IL-33, IL-6, IL-17E, IL-27, IL-31, TNF-a and TNF-b were differentially expressed in BA patients, and the AUC of MIP3a was higher than other markers. MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA. The diagnostic value of MIP3a was further confirmed in our validation study. CONCLUSION MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA.
Collapse
Affiliation(s)
- Peisong Chen
- Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Zhihai Zhong
- Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Hong Jiang
- Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Huadong Chen
- Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Junjian Lyu
- Department of Neonatal Surgery, Guangzhou Women and Children's Medical Center, PR China.
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, PR China.
| |
Collapse
|
|
49
|
Yang L, Zhou Y, Xu P, Mourya R, Lei H, Cao G, Xiong X, Xu H, Duan X, Wang N, Fei L, Chang X, Zhang X, Jiang M, Bezerra JA, Tang S. Diagnostic Accuracy of Serum Matrix Metalloproteinase-7 for Biliary Atresia. Hepatology 2018; 68:2069-2077. [PMID: 30153340 PMCID: PMC6519383 DOI: 10.1002/hep.30234] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 08/10/2018] [Indexed: 02/02/2023]
Abstract
The diagnosis of biliary atresia (BA) remains a clinical challenge because affected infants have signs, symptoms, and serum liver biochemistry that are also seen in those with other causes of neonatal cholestasis (non-BA). However, an early diagnosis and prompt surgical treatment are required to improve clinical outcome. Recently, the relative abundance of serum matrix metalloproteinase-7 (MMP-7) was suggested to have discriminatory features for infants with BA. To test the hypothesis that elevated serum concentration of MMP-7 is highly diagnostic for BA, we determined the normal serum concentration of MMP-7 in healthy control infants, and then in 135 consecutive infants being evaluated for cholestasis. The median concentration for MMP-7 was 2.86 ng/mL (interquartile range, IQR: 1.32-5.32) in normal controls, 11.47 ng/mL (IQR: 8.54-24.55) for non-BA, and 121.1 ng/mL (IQR: 85.42-224.4) for BA (P < 0.0001). The area under the curve of MMP-7 for the diagnosis of BA was 0.9900 with a cutoff value of 52.85 ng/mL; the diagnostic sensitivity and specificity were 98.67% and 95.00%, respectively, with a negative predictive value of 98.28%. Conclusion: Serum MMP-7 assay has high sensitivity and specificity to differentiate BA from other neonatal cholestasis, and may be a reliable biomarker for BA.
Collapse
Affiliation(s)
- Li Yang
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children’s Hospital Medical CenterCincinnatiOH
| | - Ying Zhou
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Pei‐pei Xu
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Reena Mourya
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children’s Hospital Medical CenterCincinnatiOH
| | - Hai‐yan Lei
- Department of Pediatric SurgeryWuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Guo‐qing Cao
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Xiao‐li Xiong
- Department of Traditional Chinese MedicineWuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Hui Xu
- Department of PediatricsHubei Women and Children’s HospitalWuhanChina
| | - Xu‐fei Duan
- Department of Pediatric SurgeryWuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Na Wang
- Department of PediatricsUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Lin Fei
- Division of Biostatistics and EpidemiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH
| | - Xiao‐pan Chang
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Xi Zhang
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Meng Jiang
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Jorge A. Bezerra
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children’s Hospital Medical CenterCincinnatiOH
| | - Shao‐tao Tang
- Department of Pediatric SurgeryUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| |
Collapse
|
|
50
|
Lertudomphonwanit C, Mourya R, Fei L, Zhang Y, Gutta S, Yang L, Bove KE, Shivakumar P, Bezerra JA. Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia. Sci Transl Med 2018; 9:9/417/eaan8462. [PMID: 29167395 DOI: 10.1126/scitranslmed.aan8462] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Accepted: 10/20/2017] [Indexed: 12/24/2022]
Abstract
Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time-consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with γ-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and an experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target.
Collapse
Affiliation(s)
- Chatmanee Lertudomphonwanit
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA.,Division of Gastroenterology and Hepatology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Reena Mourya
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Lin Fei
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Yue Zhang
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Sridevi Gutta
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Li Yang
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA.,Division of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Kevin E Bove
- Division of Pathology, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Pranavkumar Shivakumar
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA
| | - Jorge A Bezerra
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3031, USA.
| |
Collapse
|