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Wang Y, Shen Q, Yan R, Wang M, Xu M, Chen H, Li D. The Association Between Neonatal Respiratory Distress Syndrome and Plasma IgG N-Glycosylation: A Case-Control Study. J Inflamm Res 2025; 18:6439-6451. [PMID: 40416708 PMCID: PMC12103862 DOI: 10.2147/jir.s524188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 05/13/2025] [Indexed: 05/27/2025] Open
Abstract
Background Neonatal respiratory distress syndrome (NRDS) is the leading cause of neonatal death. Changes in plasma immunoglobulin G (IgG) N-glycosylation have been demonstrated in a variety of diseases. However, its implications and clinical significance in NRDS remain to be clarified. Methods To determine the effect of IgG N-glycosylation on NRDS, we recruited 88 NRDS participants and 120 control participants from December 2021 to September 2022. Plasma was collected, IgG was isolated and purified, and the glycogram was analyzed by ultra performance liquid chromatography (UPLC) with fluorescence detector. Results The occurrence of premature rupture of membranes (PROM) [OR=9.043(1.036-78.966), P=0.046] and the elevation of γ-glutamyltransferase (GGT) [OR=1.015(1.001-1.029), P=0.032] were independent risk factors for the occurrence of NRDS. Furthermore, the area percentages of GP1, GP3, GP4, GP11, GP13, and GP24 were significantly higher in NRDS patients compared with control group. Conversely, GP14 was observed to be significantly lower. Furthermore, an increase in plasma IgG sialylation and core fucosylation was observed in NRDS, whereas the modification with galactosylation was decreased. The model constructed using GP1, GP13, GP14, PROM, and GGT as composite indices demonstrated robust predictive performance (AUC=0.902, 95% CI: 0.851-0.953). Conclusion Patients with NRDS frequently exhibit alterations in the glycosylation of plasma IgG. These findings provide new insights into the diagnosis of NRDS and clinical treatment.
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Affiliation(s)
- Yingjie Wang
- Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong, People’s Republic of China
- School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
| | - Qingqing Shen
- Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, People’s Republic of China
| | - Ruxu Yan
- Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong, People’s Republic of China
- School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
| | - Meng Wang
- School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
- Jinshan District Center for Disease Control and Prevention, Shanghai, People’s Republic of China
| | - Min Xu
- Department of neonatology, Tai’an Maternal and Child Health Hospital, Tai’an, Shandong, People’s Republic of China
| | - Hanxiang Chen
- Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong, People’s Republic of China
| | - Dong Li
- School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China
- Jining Medical University, Jining, Shandong, People’s Republic of China
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Carter SWD, Kemp MW. A review of the potential off-target effects of antenatal steroid exposures on fetal development. J Dev Orig Health Dis 2025; 16:e18. [PMID: 40135629 DOI: 10.1017/s2040174425000078] [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] [Indexed: 03/27/2025]
Abstract
Antenatal steroids (ANS) are one of the most widely prescribed medications in pregnancy, being administered to women at risk of preterm delivery. In the setting of preterm delivery at or below 35 weeks' gestation, systematic review data show ANS reduce perinatal morbidity and mortality, primarily by promoting fetal lung maturation. However, with the expanding use of this intervention has come a growing appreciation for the potential off-target, adverse effects of ANS therapy on wider fetal development. We undertook a narrative literature review of the animal and clinical literature to assess current evidence for adverse effects of ANS exposure and fetal development. This review presents a summary of the evidence relating to the potential for wide-ranging, off-target, adverse effects of ANS therapy on fetal development and programming. We highlight an urgent need for further animal and clinical studies investigating the effects of ANS on the fetal immune, cardiovascular, renal and hepatic systems given a current sparsity of evidence. We also strongly suggest an emphasis on open disclosure, discussion and education of clinicians and patients with regard to the potential benefits and risks of ANS therapy, particularly in late preterm and term gestations where infants derive relatively few benefits from these drugs. We also propose further studies on the optimisation of ANS therapy through improved patient selection and improved dosing regimens based on a pharmacokinetic-pharmacodynamic informed understanding of ANS action on the fetal lung.
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Affiliation(s)
- Sean W D Carter
- Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore
- King Edward Memorial Hospital, Perth, Western Australia, Australia
- Women and Infants Research Foundation, Perth, Western Australia, Australia
| | - Matthew W Kemp
- Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore
- Women and Infants Research Foundation, Perth, Western Australia, Australia
- Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
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Wu Y, Zhou J, Zhang J, Li H. Cytokeratin 18 in nonalcoholic fatty liver disease: value and application. Expert Rev Mol Diagn 2024; 24:1009-1022. [PMID: 39387822 DOI: 10.1080/14737159.2024.2413941] [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: 02/07/2024] [Accepted: 10/04/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medical requirements, and lifestyle changes are the most basic strategy. Thus, early detection of NAFLD and timely lifestyle interventions are highly important. AREAS COVERED The traditional diagnostic methods for NAFLD are limited by accuracy, cost, and security issues. Cytokeratin 18 (CK18), which is a marker of apoptosis and overall cell death, is an excellent biomarker for NAFLD. Liver fat accumulation in NAFLD triggers the activation of caspases, which increases the CK18 cleavage and its release into the blood. CK18 can help diagnose different stages of NAFLD, especially the nonalcoholic steatohepatitis (NASH) stage. In evaluating the efficacy of the NAFLD treatment and predicting the risk of NAFLD-related diseases, CK18 plays a significant role. EXPERT OPINION CK18 can non-invasively monitor the pathological conditions of NAFLD patients and provide new hope for the early diagnosis of NAFLD. Adding CK18 to the NAFLD diagnostic criteria that are widely used in clinical settings may be efficient for the detection of NAFLD and early effective intervention.
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Affiliation(s)
- Yuan Wu
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jing Zhou
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jun Zhang
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Hongshan Li
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
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Zhang G, Wang H, Hu J, Yang C, Tan B, Hu J, Zhang M. A nomogram for predicting choledochal cyst with perforation. Pediatr Surg Int 2024; 40:129. [PMID: 38727920 PMCID: PMC11087341 DOI: 10.1007/s00383-024-05710-3] [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: 04/21/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Choledochal cyst with perforation (CC with perforation) rarely occurs, early diagnosis and timely treatment plan are crucial for the treatment of CC with perforation. This study aims to forecast the occurrence of CC with perforation. METHODS All 1111 patients were conducted, who underwent surgery for choledochal cyst at our hospital from January 2011 to October 2022. We conducted univariate and multivariate logistic regression analysis to screen for independent predictive factors for predicting CC with perforation, upon which established a nomogram. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) curves. RESULTS The age of children with choledochal cyst perforation is mainly concentrated between 1 and 3 years old. Logistic regression analysis indicates that age, alanine aminotransferase, glutamyl transpeptidase, C-reactive protein, vomiting, jaundice, abdominal distension, and diarrhea are associated with predicting the occurrence of choledochal cyst perforation. ROC curves, calibration plots, and DCA curve analysis curves demonstrate that the nomogram has great discriminative ability and calibration, as well as significant clinical utility. CONCLUSION The age of CC with perforation is mainly concentrated between 1 and 3 years old. A nomogram for predicting the perforation of choledochal cyst was established.
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Affiliation(s)
- Guangwei Zhang
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Haoming Wang
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Jianyang Hu
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Chenyu Yang
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Bingqian Tan
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Jiqiang Hu
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Mingman Zhang
- Department of Hepatobiliary Surgery, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
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Chen K, Zhang S, Cai D, Zhang Y, Jin Y, Luo W, Huang Z, Hu D, Gao Z. Clinical characteristics of choledochal cysts with intrahepatic bile duct dilatations: an observational study. Ann Surg Treat Res 2024; 106:225-230. [PMID: 38586557 PMCID: PMC10995834 DOI: 10.4174/astr.2024.106.4.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 01/10/2024] [Accepted: 02/06/2024] [Indexed: 04/09/2024] Open
Abstract
Purpose Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.
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Affiliation(s)
- Ken Chen
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Shuhao Zhang
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Duote Cai
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Yuebin Zhang
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Yi Jin
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Wenjuan Luo
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Zongwei Huang
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Di Hu
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Zhigang Gao
- Department of General Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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Alhebbi H, El-Edreesi M, Abanemai M, Saadah O, Alhatlani M, Halabi H, Bader R, Sarkhy AA, Aladsani A, Wali S, Alguofi T, Alkhathran N, NasserAllah A, Bashir MS, Al-Hussaini A. Clinical and laboratory features of biliary atresia and patterns of management practices: Saudi national study (2000-2018). Saudi J Gastroenterol 2024; 30:89-95. [PMID: 37706420 PMCID: PMC10980299 DOI: 10.4103/sjg.sjg_151_23] [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: 04/12/2023] [Revised: 07/27/2023] [Accepted: 07/29/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND We utilized the data from the Saudi national biliary atresia (BA) study (2000-2018) to describe the clinical, biochemical, imaging, and histopathological features of BA and the perioperative clinical practices among local pediatric gastroenterologists. METHODS This is a retrospective, multicenter, nationwide study that included 10 tertiary care governmental hospitals including the four liver transplant (LT) centers in different regions across Saudi Arabia. RESULTS BA was diagnosed in 204 infants (106 females; 10% preterm). The median age at referral was 65 days. Congenital anomalies were present in 68 patients (33%); 22 were splenic malformation (10.8%). The medians of laboratory investigations were total bilirubin (189 μmol/l), direct bilirubin (139 μmol/l), ALT (164 u/l), and GGT (472 u/l). The level of serum GGT was normal in 26 cases (12.7%). The ultrasound findings included hypoplastic or atrophic gall bladder (GB) (65%), normal GB (30%), and cord sign (5%). A HIDA scan was performed in 99 cases (48.52%). Magnetic resonance cholangiopancreatography (MRCP) was performed in 27 cases (13%). A total of 179 liver biopsies (88%) were obtained. The most common histopathologic findings were bile duct proliferation (92%), canalicular cholestasis (96%), bile plugs (84%), and portal fibrosis (95%). Cholangiography was performed in 139 cases (68%): operative in 122 (60%) and percutaneous in 17 (8%). A total of 143 children (70%) underwent Kasai portoenterostomy (KPE) at a median age of 70 days. After KPE, steroid was used in 37% of the cases and 100 cases (70%) were prescribed prophylactic antibiotics for variable duration (ranging between 3 and 12 months). CONCLUSION Our data show marked variation in the diagnostic evaluation and perioperative management of BA cases among the different tertiary centers. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize pre- and postoperative clinical practices. Additionally, normal serum GGT level, normal GB size on ultrasound, and being a premature baby should not preclude the diagnostic workup for BA.
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Affiliation(s)
- Homoud Alhebbi
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Mohammed El-Edreesi
- Division of Pediatric Gastroenterology, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Mohammed Abanemai
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Omar Saadah
- Division of Pediatric Gastroenterology, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Maher Alhatlani
- Al Imam Abdulrahman Bin Faisal Hospital, Ministry of National Guard Health Affairs, Dammam, Saudi Arabia
| | - Hana Halabi
- Maternity and Children’s Hospital, Makkah, Saudi Arabia
| | - Razan Bader
- Multi-organ Transplant Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Ahmed Al Sarkhy
- Department of Pediatrics, Gastroenterology Division, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Ahmed Aladsani
- Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Sami Wali
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Talal Alguofi
- Organ Transplant Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Nawaf Alkhathran
- Division of Pediatric Gastroenterology, Children’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | | | - Muhammed Salman Bashir
- Department of Biostatistics, Research Services Administration, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdulrahman Al-Hussaini
- Division of Pediatric Gastroenterology, Children’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Prince Abdullah Bin Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
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Abanemai M, AlEdreesi M, Al Sarkhy A, Saadah OI, Alhebbi H, Bader R, Alhatlani M, Halabi H, Aladsani A, Wali S, Alguofi T, Alsayed F, NasserAllah A, Almehmadi A, Qurban A, Bashir MS, Alamri A, Al-Hussaini A. Predictors of biliary atresia outcome: Saudi National Study (2000 - 2018). Saudi J Gastroenterol 2023; 29:286-294. [PMID: 37787348 PMCID: PMC10645002 DOI: 10.4103/sjg.sjg_512_22] [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: 11/25/2022] [Revised: 01/18/2023] [Accepted: 01/21/2023] [Indexed: 03/25/2023] Open
Abstract
Background Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes. Methods One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival. Results Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome. Conclusion Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome.
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Affiliation(s)
- Mohammed Abanemai
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mohammed AlEdreesi
- Women and Children’s Health Institute, Specialty Pediatrics Division, Pediatric Gastroenterology, Johns Hopkins Aramco Healthcare, Jeddah, Saudi Arabia
| | - Ahmed Al Sarkhy
- Department of Pediatrics, Gastroenterology Division, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Omar I. Saadah
- Pediatric Gastroenterology Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Homoud Alhebbi
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Razan Bader
- Multi-organ Transplant Center, King Fahad Specialist Hospital, Dammam, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Maher Alhatlani
- Al Imam Abdulrahman Bin Faisal Hospital, Ministry of National Guard Health Affairs, Dammam, Saudi Arabia
| | - Hana Halabi
- Maternity and Children’s Hospital, Makkah, Saudi Arabia
| | - Ahmed Aladsani
- Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Sami Wali
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Talal Alguofi
- Organs Transplant Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Fahad Alsayed
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | | | - Afnan Qurban
- Maternity and Children’s Hospital, Makkah, Saudi Arabia
| | - Muhammed Salman Bashir
- Department of Biostatistics, Research Services Administration, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Aisha Alamri
- East Jeddah General Hospital, Jeddah, Saudi Arabia
| | - Abdulrahman Al-Hussaini
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Division of Pediatric Gastroenterology, Children’s Specialized Hospital, Riyadh, Saudi Arabia
- Prince Abdullah Bin Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
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Gardin A, Mussini C, Héron B, Schiff M, Brassier A, Dobbelaere D, Broué P, Sevin C, Vanier MT, Habes D, Jacquemin E, Gonzales E. A Retrospective Multicentric Study of 34 Patients with Niemann-Pick Type C Disease and Early Liver Involvement in France. J Pediatr 2023; 254:75-82.e4. [PMID: 36265573 DOI: 10.1016/j.jpeds.2022.10.015] [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: 08/11/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 12/05/2022]
Abstract
OBJECTIVE To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder. STUDY DESIGN Patients with genetically confirmed NP-C (NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining. RESULTS At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients. CONCLUSIONS Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.
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Affiliation(s)
- Antoine Gardin
- Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France.
| | - Charlotte Mussini
- Department of Pathology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
| | - Bénédicte Héron
- Department of Pediatric Neurology, Reference Center for Lysosomal Diseases, Armand Trousseau-La Roche Guyon Hospital, Assistance Publique-Hôpitaux de Paris, Fédération Hospitalo-Universitaire I2-D2, Sorbonne-Université, Paris, France
| | - Manuel Schiff
- Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Filière G2M, Paris, France; Inserm UMR S1163, Institut Imagine, Université Paris Cité, Paris, France
| | - Anaïs Brassier
- Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Filière G2M, Paris, France
| | - Dries Dobbelaere
- Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Children's Hospital and Research Team for Rare Metabolic and Developmental Diseases (RADEME), EA 7364 CHRU Lille, Lille, France; MetabERN
| | - Pierre Broué
- Department of Pediatric Hepatology, Reference Center for Inborn Error of Metabolism, Toulouse Children Hospital, Toulouse, France
| | - Caroline Sevin
- Department of Pediatric Neurology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
| | - Marie T Vanier
- Inserm U820, Laboratoire Gillet-Mérieux, Hospices Civils de Lyon, Lyon, France
| | - Dalila Habes
- Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France
| | - Emmanuel Jacquemin
- Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR S1193, Université Paris-Saclay, Hépatinov, Orsay, France
| | - Emmanuel Gonzales
- Pediatric Hepatology and Liver Transplant Department, Centre de Référence de l'Atrésie des Voies Biliaires et des Cholestases Génétiques, European Reference Network RARE-LIVER, Filière de Santé des Maladies Rares du Foie de l'Enfant et de l'Adulte, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France; Inserm UMR S1193, Université Paris-Saclay, Hépatinov, Orsay, France
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9
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Al-Hussaini A, Asery A, Alharbi O. Urinary coproporphyrins as a diagnostic biomarker of Dubin-Johnson syndrome in neonates: A diagnostic pathway is proposed. Saudi J Gastroenterol 2023:369068. [PMID: 36751849 DOI: 10.4103/sjg.sjg_480_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Dubin-Johnson syndrome (DJS) presents during the neonatal period with a phenotype that overlaps with a broad list of causes of neonatal cholestasis (NC), which makes the identification of DJS challenging for clinicians. We conducted a case-controlled study to investigate the utility of urinary coproporphyrins (UCP) I% as a potential diagnostic biomarker. METHODS We reviewed our database of 533 cases of NC and identified 28 neonates with disease-causing variants in ATP-binding cassette-subfamily C member 2 (ABCC2) gene "Cases" (Study period 2008-2019). Another 20 neonates with cholestasis due to non-DJS diagnoses were included as "controls." Both groups underwent UCP analysis to measure CP isomer I percentage (%). RESULTS Serum alanine aminotransferase (ALT) levels were within the normal range in 26 patients (92%) and mildly elevated in 2 patients. ALT levels were significantly lower in neonates with DJS than in NC from other causes (P < 0.001). The use of normal serum ALT levels to predict DJS among neonates with cholestasis had a sensitivity of 93%, specificity 90%, positive predictive value (PPV) 34%, and negative predictive value (NPV) 99.5%. The median UCPI% was significantly higher in DJS patients [88%, interquartile range (IQR) 1-IQR3, 84.2%-92.7%] than in NC from other causes [67%, (IQR1-IQR3, 61%-71.5%; Confidence interval 0.18-0.28; P< 0.001)]. The use of UCPI% >80% to predict DJS had a sensitivity, specificity, PPV, and NPV of 100%. CONCLUSION Based on the results from our study, we propose sequencing of the ABCC2 gene in neonates with normal ALT, presence of cholestasis and UCP1% >80%.
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Affiliation(s)
- Abdulrahman Al-Hussaini
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City College of Medicine, Alfaisal University; Prince Abdullah bin Khalid Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Ali Asery
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Omar Alharbi
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
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10
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Berhane B, van Rheenen PF, Verkade HJ. Gamma-glutamyl transferase and disease course in pediatric-onset primary sclerosing cholangitis: A single-center cohort study. Health Sci Rep 2023; 6:e1086. [PMID: 36751275 PMCID: PMC9892024 DOI: 10.1002/hsr2.1086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/29/2022] [Accepted: 01/16/2023] [Indexed: 02/05/2023] Open
Abstract
Background and Aims Patients with pediatric-onset primary sclerosing cholangitis (PSC) are at risk of developing hepatic complications with liver transplantation as only curative treatment. Complications usually occur over many years, underlining the need for reliable surrogate markers to predict the clinical course. Recently, gamma-glutamyl transferase (GGT) has been suggested to allow prediction of the clinical course. In a single-center cohort study, we tested the potency of GGT in this respect. Methods We used longitudinal data of patients from our academic center, diagnosed with pediatric-onset PSC between 2000 and 2020. Patients with a GGT decrease from baseline >25% (n = 36) were compared with those who did not have this decrease (n = 7). We performed Kaplan-Meier analysis and log-rank testing to assess the occurrence of portal hypertensive or biliary complications, hepatobiliary malignancies, liver transplantation, or death. Results The median age diagnosis was 15.2 years and 12.1 years in the group with ≤25% decrease of GGT and the group with >25% decrease, respectively (p = 0.078). The probability of developing ≥1 complications in the first 5 years after diagnosis was 50% in the group with ≤25% decrease of GGT and 20% in the group with >25% decrease of GGT (p = 0.031). The use of medication was not associated with the development of complications. Conclusion In a retrospective cohort study, we report that a GGT decrease of >25% within 1 year of diagnosis of pediatric-onset PSC is associated with a lower occurrence of complications within 5 years. Our results provide further support for the recently hypothesized predictive value of first-year GGT change in predicting the disease course in pediatric-onset PSC.
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Affiliation(s)
- Besrat Berhane
- Pediatric Gastroenterology & Hepatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Patrick F. van Rheenen
- Pediatric Gastroenterology & Hepatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Henkjan J. Verkade
- Pediatric Gastroenterology & Hepatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
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11
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Muñoz-Prieto A, Cerón JJ, Rubio CP, Contreras-Aguilar MD, Pardo-Marín L, Ayala-de la Peña I, Martín-Cuervo M, Holm Henriksen IM, Arense-Gonzalo JJ, Tecles F, Hansen S. Evaluation of a Comprehensive Profile of Salivary Analytes for the Diagnosis of the Equine Gastric Ulcer Syndrome. Animals (Basel) 2022; 12:ani12233261. [PMID: 36496782 PMCID: PMC9740180 DOI: 10.3390/ani12233261] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/14/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022] Open
Abstract
In this report, the measurement of salivary biomarkers as an aid for diagnosis of equine gastric ulcer syndrome (EGUS) was studied. A comprehensive panel of 23 salivary analytes was measured in the saliva of horses affected by EGUS and compared to healthy animals and horses with other diseases clinically similar to EGUS but with a negative diagnosis at gastroscopic examination. A total of 147 horses were included in the study and divided into heathy population (n = 12), the EGUS group (n = 110), and the group of horses with other diseases (n = 25). From the 23 analytes studied, 17 showed increased values in EGUS horses when compared to healthy ones, and uric acid, triglycerides, and calcium were significantly increased in horses with EGUS compared to the group of other diseases. The receiver operating characteristic curve analyses showed a modest but significant discriminatory power of those three analytes to identify EGUS from other diseases with similar symptoms. The discriminatory power enhanced when the results of the three analytes were combined. In conclusion, the results showed that selected salivary analytes could have potential use as biomarkers in horses with EGUS.
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Affiliation(s)
- Alberto Muñoz-Prieto
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
- Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - José J. Cerón
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
| | - Camila P. Rubio
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
| | - María Dolores Contreras-Aguilar
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
| | - Luis Pardo-Marín
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
| | - Ignacio Ayala-de la Peña
- Animal Medicine and Surgery Department, Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
| | - María Martín-Cuervo
- Animal Medicine, Faculty of Veterinary Medicine of Cáceres, University of Extremadura, Av. de la Universidad S-N, 10005 Cáceres, Spain
| | - Ida-Marie Holm Henriksen
- Department of Veterinary Clinical Sciences, Veterinary School of Medicine, Sektion Medicine and Surgery, University of Copenhagen, Hoejbakkegaard Allé 5, DK-2630 Høje-Taastrup, Denmark
| | - Julián J. Arense-Gonzalo
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar, 30120 Murcia, Spain
- Division of Preventive Medicine and Public Health Sciences, School of Medicine, University of Murcia, Espinardo, 30100 Murcia, Spain
| | - Fernando Tecles
- Interdisciplinary Laboratory of Clinical Analysis of the University of Murcia (Interlab-UMU), Regional Campus of International Excellence ‘Campus Mare Nostrum’, University of Murcia, Campus de Espinardo s/n, Espinardo, 30100 Murcia, Spain
- Correspondence: ; Tel.: +34-868887082
| | - Sanni Hansen
- Department of Veterinary Clinical Sciences, Veterinary School of Medicine, Sektion Medicine and Surgery, University of Copenhagen, Hoejbakkegaard Allé 5, DK-2630 Høje-Taastrup, Denmark
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12
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Ilott NE, Neyazi M, Oxford Translational Gastroenterology Unit Investigators, Arancibia-Cárcamo CV, Powrie F, Geremia A. Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease. Wellcome Open Res 2022; 6:199. [PMID: 36447600 PMCID: PMC9664024 DOI: 10.12688/wellcomeopenres.16901.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2022] [Indexed: 06/30/2024] Open
Abstract
Background: Patients with primary sclerosing cholangitis (PSC) frequently have co-ocurring ulcerative colitis (UC) and develop colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Understanding the molecular and microbial basis for differences between these two patient groups and how these vary across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (ileum n = 7, caecum n = 7, rectum n = 7), UC (ileum n = 9, caecum n = 10, rectum n = 10) and healthy controls (ileum n = 11, caecum n = 9, rectum n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.
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Affiliation(s)
- Nicholas E. Ilott
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
| | - Mastura Neyazi
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Oxford Translational Gastroenterology Unit Investigators
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Carolina V. Arancibia-Cárcamo
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Fiona Powrie
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Alessandra Geremia
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
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13
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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.
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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
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14
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Quelhas P, Jacinto J, Cerski C, Oliveira R, Oliveira J, Carvalho E, dos Santos J. Protocols of Investigation of Neonatal Cholestasis-A Critical Appraisal. Healthcare (Basel) 2022; 10:2012. [PMID: 36292464 PMCID: PMC9602084 DOI: 10.3390/healthcare10102012] [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: 08/29/2022] [Revised: 10/06/2022] [Accepted: 10/08/2022] [Indexed: 11/04/2022] Open
Abstract
Neonatal cholestasis (NC) starts during the first three months of life and comprises extrahepatic and intrahepatic groups of diseases, some of which have high morbimortality rates if not timely identified and treated. Prolonged jaundice, clay-colored or acholic stools, and choluria in an infant indicate the urgent need to investigate the presence of NC, and thenceforth the differential diagnosis of extra- and intrahepatic causes of NC. The differential diagnosis of NC is a laborious process demanding the accurate exclusion of a wide range of diseases, through the skillful use and interpretation of several diagnostic tests. A wise integration of clinical-laboratory, histopathological, molecular, and genetic evaluations is imperative, employing extensive knowledge about each evaluated disease as well as the pitfalls of each diagnostic test. Here, we review the difficulties involved in correctly diagnosing the cause of cholestasis in an affected infant.
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Affiliation(s)
- Patricia Quelhas
- Faculty of Health Sciences, Health Science Investigation Center of University of Beira Interior (CICS-UBI), 6200-506 Covilha, Portugal
| | - Joana Jacinto
- Medicine Department, University of Beira Interior (UBI), Faculty of Health Sciences, 6201-001 Covilha, Portugal
| | - Carlos Cerski
- Pathology Department of Universidade Federal do Rio Grande do Sul (UFRGS), Pathology Service of Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Brazil
| | - Rui Oliveira
- Centro de Diagnóstico Histopatológico (CEDAP), 3000-377 Coimbra, Portugal
| | - Jorge Oliveira
- Center for Predictive and Preventive Genetics (CGPP), IBMC, UnIGENe, i3S, University of Porto, 4200-135 Porto, Portugal
| | - Elisa Carvalho
- Department of Gastroenterology and Hepatology, Hospital de Base do Distrito Federal, Hospital da Criança de Brasília, Brasília 70330-150, Brazil
| | - Jorge dos Santos
- Faculty of Health Sciences, Health Science Investigation Center of University of Beira Interior (CICS-UBI), 6200-506 Covilha, Portugal
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15
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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.
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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.
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16
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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.
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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.
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17
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Shin YJ, Godin R, Walters RA, Niu J, Kahn DJ. Effect of Phenobarbital on Elevated Direct Bilirubin Concentrations in Neonates and Infants in the Neonatal Intensive Care Unit. J Pediatr Pharmacol Ther 2022; 27:545-550. [DOI: 10.5863/1551-6776-27.6.545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/24/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVE
Few studies have evaluated the effect of phenobarbital (PB) on elevated direct bilirubin (DB) plasma concentrations in neonates and infants, and none have compared its effect with a control group with matched study baseline DB values. The purpose of this study was to quantify changes in elevated DB plasma concentrations (≥2 mg/dL) in neonates and infants between a PB-treated and control group.
METHODS
A retrospective, observational, matched, cohort study was performed comparing patients between a PB-treated group and a control group with similar study baseline plasma DB values ≥2 mg/dL over an 8-week period. The percent change in DB plasma concentrations from study baseline was compared for each week of the study period.
RESULTS
During the 8-year study period, 310 patients had DB plasma concentrations ≥2 mg/dL, of which 26 remained in each group after exclusions. The PB group had increased DB concentrations and the control group had decreased DB concentrations when compared with their study baseline DB concentrations each week of the study period. By study end, the mean DB concentration increased by 11.2% in the PB group and decreased by 48.5% in the control group (p = 0.02). In multiple regression analysis, only birth weight (standardized coefficient = 0.44, p = 0.02), and gastrointestinal obstruction (standardized coefficient = −0.4, p = 0.03) were associated with significant percent change in DB concentrations.
CONCLUSIONS
This study demonstrated PB does not improve cholestasis in neonates and infants.
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Affiliation(s)
- Young J. Shin
- Department of Pharmacy (YJS, RG, RAW), Joe DiMaggio Children's Hospital, Hollywood, FL
| | - Robert Godin
- Department of Pharmacy (YJS, RG, RAW), Joe DiMaggio Children's Hospital, Hollywood, FL
| | - Ryan A. Walters
- Department of Pharmacy (YJS, RG, RAW), Joe DiMaggio Children's Hospital, Hollywood, FL
| | - Jianli Niu
- Office of Human Research, Memorial Healthcare System (JN), Hollywood, FL
| | - Doron J. Kahn
- Division of Neonatology (DJK), Joe DiMaggio Children's Hospital, Hollywood, FL
- Pediatrix Medical Group (DJK), Sunrise, FL
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18
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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.
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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
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19
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Kalas MA, Chavez L, Leon M, Taweesedt PT, Surani S. Abnormal liver enzymes: A review for clinicians. World J Hepatol 2021; 13:1688-1698. [PMID: 34904038 PMCID: PMC8637680 DOI: 10.4254/wjh.v13.i11.1688] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/24/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting, especially with the automatization of testing in this technological era. These tests include aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time and international normalized ratio (INR). Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation. Generally, abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild [< 5 × upper limit of normal (ULN)], moderate (> 5-< 15 × ULN) and severe (> 15 × ULN). Hepatocellular pattern causes include but are not limited to; non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, alcohol use, chronic viral hepatitis, liver cirrhosis (variable), autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, celiac disease, medication-induced and ischemic hepatitis. Cholestatic pattern causes include but is not limited to; biliary pathology (obstruction, autoimmune), other conditions with hyperbilirubinemia (conjugated and unconjugated). It is crucial to interpret these commonly ordered tests accurately as appropriate further workup, treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.
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Affiliation(s)
- M Ammar Kalas
- Department of Internal Medicine, Texas Tech University Health Science Center, El Paso, TX 79905, United States
| | - Luis Chavez
- Department of Internal Medicine, Texas Tech University Health Science Center, El Paso, TX 79905, United States
| | - Monica Leon
- Department of General Surgery, University of Mexico, Ciudad de Mexico 01120, Mexico
| | - Pahnwat Tonya Taweesedt
- Department of Medicine, Corpus Christi Medical Center, Corpus Christi, TX 78412, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States.
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20
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Al-Hussaini A, Lone K, Bashir MS, Alrashidi S, Fagih M, Alanazi A, AlYaseen S, Almayouf A, Alruwaithi M, Asery A. ATP8B1, ABCB11, and ABCB4 Genes Defects: Novel Mutations Associated with Cholestasis with Different Phenotypes and Outcomes. J Pediatr 2021; 236:113-123.e2. [PMID: 33915153 DOI: 10.1016/j.jpeds.2021.04.040] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 04/17/2021] [Accepted: 04/20/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To characterize the clinical, laboratory, histologic, molecular features, and outcome of gene-confirmed progressive familial intrahepatic cholestasis (PFIC) 1-3 among Arabs and to evaluate for "genotype-phenotype" correlations. STUDY DESIGN We retrospectively reviewed charts of 65 children (ATP8B1 defect = 5, ABCB11 = 35, ABCB4 = 25) who presented between 2008 and 2019 with cholestasis. The clinical phenotype of a disease was categorized based on response of cholestasis and itching to ursodeoxycholic acid and ultimate outcome, into mild (complete response), intermediate (partial response, nonprogressive), and severe (progression to end-stage liver disease). RESULTS Overall, 27 different mutations were identified (ATP8B1, n = 5; ABCB11, n = 11; ABCB4, n = 11), comprising 10 novel ones. Six patients with heterozygous missense mutations (ATP8B1, n = 2; ABCB11, n = 4) had transient cholestasis. Of the remaining 3 patients with PFIC1, 2 developed severe phenotype (splicing and frameshift mutations). Of the remaining 31 patients with PFIC2, 25 developed severe disease (15 due to frameshift and splicing mutations). Of 25 patients with PFIC3, 10 developed a severe phenotype (1 splicing and 3 frameshift mutations; 6 missense). Patients with PFIC2 had significantly shorter survival time and more rapid disease progression than patients with PFIC3 (P < .001). Patients with frameshift mutations in ABCB11 gene (p.Thr127Hisfs∗6) and ABCB4 gene (p.Phe210Serfs∗5) had significantly shorter survival time than missense mutations (P = .011; P = .0039, respectively). CONCLUSIONS We identified genotype-phenotype correlations among mutations in ABCB11 and ABCB4 genes, which underscore the prognostic value of early genetic diagnosis. The disease course in patients with PFIC3 could be favorably modified by ursodeoxycholic acid therapy.
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Affiliation(s)
- Abdulrahman Al-Hussaini
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Prince Abdullah bin Khalid Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Khurram Lone
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Muhammed Salman Bashir
- Department of Biostatistics, Research Services Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Sami Alrashidi
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mosa Fagih
- Department of Pathology and Laboratory Medicine, King Saud Medical City, Riyadh, Saudi Arabia
| | - Alanoud Alanazi
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Salem AlYaseen
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdulaziz Almayouf
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Muhanad Alruwaithi
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ali Asery
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
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21
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Yakupovich A, Rajeswaran S, Green J, Donaldson JS. Role of Interventional Radiology in Children with Biliary and Gallbladder Diseases. Semin Intervent Radiol 2021; 38:356-363. [PMID: 34393346 DOI: 10.1055/s-0041-1731374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Biliary and gallbladder diseases in infants and children often present unique diagnostic and therapeutic challenges that require a fundamental understanding of notable biliary diseases and anatomical variations. Surgical and endoscopic approaches that are often the gold standard in adult biliary treatment may be technically challenging and are associated with a high morbidity that may warrant a multidisciplinary treatment approach. This article will provide a comprehensive overview of the biliary conditions where interventional radiology can play a vital role in the diagnosis, management, and treatment. Differences in approach or technique between children and adults will be highlighted.
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Affiliation(s)
- Anel Yakupovich
- Department of Radiology, Rush University Medical Center, Chicago, Illinois
| | - Shankar Rajeswaran
- Department of Radiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine at Northwestern University, Chicago, Illinois
| | - Jared Green
- Department of Radiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine at Northwestern University, Chicago, Illinois
| | - James S Donaldson
- Department of Radiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine at Northwestern University, Chicago, Illinois
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22
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Ilott NE, Neyazi M, Oxford Translational Gastroenterology Unit Investigators, Arancibia-Cárcamo CV, Powrie F, Geremia A. Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease. Wellcome Open Res 2021; 6:199. [PMID: 36447600 PMCID: PMC9664024 DOI: 10.12688/wellcomeopenres.16901.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2021] [Indexed: 06/30/2024] Open
Abstract
Background: Primary sclerosing cholangitis (PSC) is a disease of the bile duct and liver. However, patients frequently have co-morbidities including inflammatory bowel disease (IBD) and colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Further, clinical and immunological features, and involved intestinal sites differ between PSC/UC and UC. Understanding the molecular and microbial basis for differences in cancer risk between these two patient groups and how these differ across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals. Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (n = 8), UC (n = 10) and healthy controls (n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC and host-microbiome associations. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 ( GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.
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Affiliation(s)
- Nicholas E. Ilott
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
| | - Mastura Neyazi
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Oxford Translational Gastroenterology Unit Investigators
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Carolina V. Arancibia-Cárcamo
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Fiona Powrie
- The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
| | - Alessandra Geremia
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
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23
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Neonatale Cholestase. Monatsschr Kinderheilkd 2021. [DOI: 10.1007/s00112-020-01042-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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24
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Lipiński P, Bogdańska A, Socha P, Tylki-Szymańska A. Liver Involvement in Congenital Disorders of Glycosylation and Deglycosylation. Front Pediatr 2021; 9:696918. [PMID: 34291020 PMCID: PMC8286991 DOI: 10.3389/fped.2021.696918] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 06/07/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Congenital disorders of glycosylation (CDG) and NGLY1-CDDG (NGLY1-congenital disorder of deglycosylation) usually represent multisystem (especially neurovisceral) diseases with liver involvement reported in some of them. The aim of the study was to characterize the liver phenotype in CDG and NGLY1-CDDG patients hospitalized in our Institute, and to find the most specific features of liver disease among them. Material and Methods: The study involved 39 patients (from 35 families) with CDG, and two patients (from two families) with NGLY1-CDDG, confirmed molecularly, for whom detailed characteristics of liver involvement were available. They were enrolled based on the retrospective analysis of their medical records. Results: At the time of the first consultation, 13/32 patients were diagnosed with hepatomegaly; none of them with splenomegaly. As many as 23/32 persons had elevated serum transaminases, including 16 (70%) who had mildly elevated levels. During the long-term follow-up (available for 19 patients), serum transaminases normalized in 15/19 (79%) of them, including a spontaneous normalization in 12/15 (80%) of them. The GGT activity was observed to be normal in all study cases. Protein C, protein S and antithrombin activities in plasma were observed in 16 patients, and they were decreased in all of them. Conclusions: It is necessary to conduct a long-term follow-up of liver disease in CDG to obtain comprehensive data.
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Affiliation(s)
- Patryk Lipiński
- Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland
| | - Anna Bogdańska
- Department of Biochemistry, Radioimmunology and Experimental Medicine, Children's Memorial Health Institute, Warsaw, Poland
| | - Piotr Socha
- Department of Gastroenterology, Hepatology, Feeding Difficulties and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland
| | - Anna Tylki-Szymańska
- Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland
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25
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Al-Hussaini A, AlSaleem B, AlHomaidani H, Asery A, Alruwaithi M, Alameer M, Afashah W, Salman BM, Almontashiri N. Clinical, Biochemical, and Molecular Characterization of Neonatal-Onset Dubin-Johnson Syndrome in a Large Case Series From the Arabs. Front Pediatr 2021; 9:741835. [PMID: 34858902 PMCID: PMC8631451 DOI: 10.3389/fped.2021.741835] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/20/2021] [Indexed: 11/22/2022] Open
Abstract
Background: There are only a few case reports and small case series on neonatal-onset Dubin-Johnson syndrome (DJS), particularly from Far-East Asia, Iranian and Moroccan Jews, and Europe. Objectives: In this first study from the Arabs and the largest series reported to date, we characterized the clinical, laboratory, and molecular features and outcome of gene-confirmed neonatal-onset DJS. Methods: We reviewed our database of 533 cases of neonatal cholestasis that presented to our center during the period from 2008 to 2019. We identified neonates with a disease-causing mutation in ABCC2 gene. Results: Twenty-eight neonates with DJS were diagnosed (5.3%). All of the 28 were full-term, well looking neonates without hepatosplenomegaly, with cholestasis, and normal liver synthetic function since the 1 week of life that resolved within 3-6 months of age, followed by a benign course punctuated by recurrent episodes of jaundice in 43% during a median follow up period of 9.25 (range 2.5-14 years). Alanine aminotransferase levels were within normal range in 26 patients (92%) and mildly elevated in two patients. ALT levels were significantly lower in neonates with DJS than in other cases with neonatal cholestasis from other causes (p < 0.001). The median urinary coproporphyrin I% was 88% (IQ1-IQ3 = 84.2-92.7%). We identified four homozygous variants in the ABCC2 gene (from 22 unrelated families), one splicing variant (c.3258+1G>A; p.?), and three were missense variants; two of which were novel missense variants [c.1594G>A (p.Glu532Lys) and c.2439G>C (p.Lys813Asn)]. The p.Gly758Val mutation has occurred in 23 patients (from 19 unrelated families). Conclusions: Our study suggests that normal ALT-cholestasis in a well-looking neonate should trigger evaluation for DJS. The p.Gly758Val variant in ABCC2 is the most predominant mutation among Arabs with "founder effects." Identification of the predominant ABCC2 variant in any population is likely to facilitate rapid molecular analysis by future targeting of that specific mutation.
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Affiliation(s)
- Abdulrahman Al-Hussaini
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.,Prince Abdullah bin Khalid Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Badr AlSaleem
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Hamad AlHomaidani
- Department of Molecular Genetics, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ali Asery
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Muhanad Alruwaithi
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mohammed Alameer
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Waleed Afashah
- The Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Bashir Muhammed Salman
- Department of Biostatistics, Research Services Administration, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Naif Almontashiri
- Center for Genetics and Inherited Diseases, Taibah University, Medina, Saudi Arabia.,Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
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26
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Xu Y, Wu Y. Atorvastatin associated with gamma glutamyl transpeptidase elevation in a hyperlipidemia patient: A case report and literature review. Medicine (Baltimore) 2020; 99:e22572. [PMID: 33019469 PMCID: PMC7535555 DOI: 10.1097/md.0000000000022572] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 07/26/2020] [Accepted: 09/07/2020] [Indexed: 12/24/2022] Open
Abstract
RATIONALE Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS Blood lipid test showed mixed dyslipidemia. INTERVENTION Atorvastatin 10 mg/day was given to the patient. OUTCOMES The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.
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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.
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Lipiński P, Ciara E, Jurkiewicz D, Pollak A, Wypchło M, Płoski R, Cielecka-Kuszyk J, Socha P, Pawłowska J, Jankowska I. Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders-Single-Center Experience. Front Pediatr 2020; 8:414. [PMID: 32793533 PMCID: PMC7393978 DOI: 10.3389/fped.2020.00414] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 06/16/2020] [Indexed: 12/19/2022] Open
Abstract
Objective: To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Study design: Patients with diagnosis of chronic cholestatic liver disease of an unknown etiology underwent NGS of targeted genes panel. Group 1 included five patients (prospectively recruited) hospitalized from January to December 2017 while group 2 included seventeen patients (retrospectively recruited) hospitalized from 2010 to 2017 presenting with low-GGT PFIC phenotype (group 2a, 11 patients) or indeterminant cholestatic liver cirrhosis (group 2b, 6 patients). Results: Among 22 patients enrolled into the study, 21 various pathogenic variants (including 11 novel) in 5 different genes (including ABCB11, ABCB4, TJP2, DGUOK, CYP27A1) were identified. The molecular confirmation was obtained in 15 out of 22 patients (68%). In group 1, two out of five patients presented with low-GGT cholestasis, and were diagnosed with BSEP deficiency. Out of three patients presenting with high-GGT cholestasis, one patient was diagnosed with PFIC-3, and the remaining two were not molecularly diagnosed. In group 2a, seven out of eleven patients, were diagnosed with BSEP deficiency and two with TJP-2 deficiency. In group 2b, three out of six patients were molecularly diagnosed; one with PFIC-3, one with CYP27A1 deficiency, and one with DGUOK deficiency. Conclusions: Panel-based NGS appears to be a very useful tool in diagnosis of monogenic cholestatic liver disorders in cases when extrahepatic causes have been primarily excluded. NGS presented the highest diagnosis rate to identify the molecular background of cholestatic liver diseases presenting with a low-GGT PFIC phenotype.
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Affiliation(s)
- Patryk Lipiński
- Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.,Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Elżbieta Ciara
- Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Dorota Jurkiewicz
- Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Agnieszka Pollak
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
| | - Maria Wypchło
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.,Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Rafał Płoski
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
| | | | - Piotr Socha
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Joanna Pawłowska
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Irena Jankowska
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
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Wadhwani SI. 50 Years Ago in TheJournalofPediatrics: The Diagnostic Value of Gamma Glutamyl Transpeptidase in Children and Adolescents with Liver Disease. J Pediatr 2019; 214:164. [PMID: 31655694 PMCID: PMC6858059 DOI: 10.1016/j.jpeds.2019.04.054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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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.
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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
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El-Shabrawi M, Abdelgawad M, Elgaddar O, Hassanin F, Khalil A, Mahfouz A, Elbanna B. A clinical and immunological study of children with chronic hepatitis B virus infection. PRZEGLAD GASTROENTEROLOGICZNY 2019; 14:211-216. [PMID: 31649794 PMCID: PMC6807666 DOI: 10.5114/pg.2019.88171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 02/14/2019] [Indexed: 01/16/2023]
Abstract
AIM To identify the clinical status and immunological profile of a cohort of children with chronic hepatitis B virus (HBV) infection to assess the short-term consequences of this infection. MATERIAL AND METHODS This prospective case-control study included 30 children in the age range 1-15 years with positive HBsAg attending the Hepatology clinic of Alexandria University Children's Hospital. Twenty children received lamivudine (3 mg/kg, oral, once a day), and 10 children were lamivudine-resistant and received entecavir treatment (10-11 kg/0.3 mg to > 30 kg/1 mg). They were followed up every 3 months for 1 year. RESULTS The study showed that 97% of the studied cases were discovered accidentally during routine investigations and only 3% presented by acute hepatitis. Ninety percent of them had family member infection with HBV, of which 70% were the mother. Eighty-seven percent of cases had no clinical signs, and only 13% of cases had hepatomegaly. All of the cases were HBsAg positive, 50% were HBeAg positive, 56.7% were HBeAb positive, 33.3% were HBcAb positive, and 100% were HBsAb negative. CONCLUSIONS Most of children with HBV infection had associated family member infection and were accidentally discovered. Despite a marked decrease in HBV DNA level after treatment, there was no clearance of HBsAg and no HBsAb seroconversion. Screening for the HBsAb level in children with family members with HBV is recommended.
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Affiliation(s)
| | - Manal Abdelgawad
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ola Elgaddar
- Medical Research Institute, Alexandria University, Alexandria, Egypt
| | | | - Ahmed Khalil
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Aml Mahfouz
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Basant Elbanna
- Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Black DD, Mack C, Kerkar N, Miloh T, Sundaram SS, Anand R, Gupta A, Alonso E, Arnon R, Bulut P, Karpen S, Lin CH, Rosenthal P, Ryan M, Squires RH, Valentino P, Elsea SH, Shneider BL. A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis. Hepatol Commun 2019; 3:1482-1495. [PMID: 31701072 PMCID: PMC6824074 DOI: 10.1002/hep4.1421] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/27/2019] [Indexed: 12/15/2022] Open
Abstract
Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma‐glutamyl transpeptidase (GGT) <2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5 IU/L (P = 0.105) and GGT, +60.4 IU/L (P = 0.003). In 7 participants, ALT and GGT ≤29 IU/L did not rise above 29 IU/L (null response group). Eight participants had increases of ALT or GGT >100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin‐8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. Conclusion: The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.
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Affiliation(s)
- Dennis D Black
- Pediatrics University of Tennessee Health Science Center Memphis TN
| | - Cara Mack
- Pediatrics University of Colorado School of Medicine Aurora CO
| | - Nanda Kerkar
- Pediatrics University of Rochester Medical Center Rochester NY.,Pediatrics Keck School of Medicine of University of Southern California Los Angeles CA
| | - Tamir Miloh
- Pediatrics Baylor College of Medicine Houston TX
| | | | | | | | - Estella Alonso
- Pediatrics Northwestern University College of Medicine Chicago IL
| | - Ronen Arnon
- Pediatrics Mount Sinai Icahn School of Medicine New York NY
| | - Pinar Bulut
- Pediatrics Phoenix Children's Hospital Phoenix AZ
| | - Saul Karpen
- Pediatrics Emory University School of Medicine Atlanta GA
| | - Chuan-Hao Lin
- Pediatrics Keck School of Medicine of University of Southern California Los Angeles CA
| | - Philip Rosenthal
- Pediatrics School of Medicine University of California, San Francisco San Francisco CA
| | - Matthew Ryan
- Pediatrics Children's Hospital of Philadelphia Philadelphia PA
| | - Robert H Squires
- Pediatrics University of Pittsburgh School of Medicine Pittsburgh PA
| | | | - Sarah H Elsea
- Molecular and Human Genetics Baylor College of Medicine Houston TX
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Nicastro E, Di Giorgio A, Marchetti D, Barboni C, Cereda A, Iascone M, D'Antiga L. Diagnostic Yield of an Algorithm for Neonatal and Infantile Cholestasis Integrating Next-Generation Sequencing. J Pediatr 2019; 211:54-62.e4. [PMID: 31160058 DOI: 10.1016/j.jpeds.2019.04.016] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/15/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the performance of a diagnostic protocol for neonatal/infantile cholestasis in which the main clinical patterns steered the early use of different genetic testing strategies. STUDY DESIGN An observational study was conducted between 2012 and 2017 in a tertiary care setting on a prospective cohort of children with cholestasis occurring at ≤1 year of age and persisting ≥6 weeks, to measure the detection rate of underlying monogenic diseases. After the exclusion of biliary atresia, a clinically driven genetic testing was performed, entailing 3 different approaches with different wideness: confirmatory single-gene testing; focused virtual panels; and wide search through trio whole-exome sequencing. RESULTS We enrolled 125 children (66 female, median age 2 months); 96 (77%) patients had hypocholic stools and were evaluated rapidly to exclude biliary atresia, which was the final diagnosis in 74 (59%). Overall, 50 patients underwent genetic testing, 6 with single confirmatory gene testing, 38 through panels, and 6 with trio whole-exome sequencing because of complex phenotype. The genetic testing detection rate was 60%: the final diagnosis was Alagille syndrome in 11, progressive familial intrahepatic cholestasis type 2 in 6, alpha-1-antitrypsin deficiency in 3, and progressive familial intrahepatic cholestasis type 3 in 2; a further 7 genetic conditions were identified in 1 child each. Overall, only 18 of 125 (14%) remained with an indeterminate etiology. CONCLUSIONS This protocol combining clinical and genetic assessment proved to be an effective diagnostic tool for neonatal/infantile cholestasis, identifying inherited disorders with a high detection rate. It also could allow a noninvasive diagnosis in children presenting with colored stools.
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Affiliation(s)
- Emanuele Nicastro
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Angelo Di Giorgio
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Daniela Marchetti
- Medical Genetics Laboratory, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Chiara Barboni
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Anna Cereda
- Clinical Genetics, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Maria Iascone
- Medical Genetics Laboratory, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Lorenzo D'Antiga
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
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Deneau MR, Mack C, Abdou R, Amin M, Amir A, Auth M, Bazerbachi F, Marie Broderick A, Chan A, DiGuglielmo M, El‐Matary W, El‐Youssef M, Ferrari F, Furuya KN, Gottrand F, Gupta N, Homan M, Jensen M, Kamath BM, Mo Kim K, Kolho K, Konidari A, Koot B, Iorio R, Martinez M, Mohan P, Palle S, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Valentino PL, Varier R, Venkat V, Vitola B, Vos MB, Woynarowski M, Yap J, Miloh T. Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis. Hepatol Commun 2018; 2:1369-1378. [PMID: 30411083 PMCID: PMC6211333 DOI: 10.1002/hep4.1251] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/13/2018] [Indexed: 12/15/2022] Open
Abstract
Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event-free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver-related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5-year event-free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5-year event-free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5-year event-free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.
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Affiliation(s)
| | - Cara Mack
- University of Colorado School of MedicineAuroraCO
| | - Reham Abdou
- Nassau University Medical CenterEast MeadowNY
| | | | - Achiya Amir
- Dana‐Dwek Children’s Hospital, Tel‐Aviv Medical Center, Tel‐Aviv UniversityTel AvivIsrael
| | - Marcus Auth
- Alder Hey Children’s HospitalLiverpoolUnited Kingdom
| | | | | | - Albert Chan
- University of Rochester Medical CenterRochesterNY
| | | | | | | | | | | | | | | | | | | | | | | | | | - Anastasia Konidari
- University of LiverpoolLiverpoolUnited Kingdom
- University of ManchesterManchesterUnited Kingdom
| | - Bart Koot
- Academic Medical CentreAmsterdamthe Netherlands
| | | | | | | | | | | | | | | | - Pushpa Sathya
- Memorial UniversitySt. John’s, Newfoundland and LabradorCanada
| | | | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLCPortlandOR
| | - Veena Venkat
- University of Pittsburgh Medical CenterPittsburghPA
| | | | | | | | | | - Tamir Miloh
- Phoenix Children’s HospitalPhoenixAZ
- Texas Children’s HospitalHoustonTX
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Gamma Glutamyl Transferase and Uric Acid Levels Can Be Associated with the Prognosis of Patients in the Pediatric Intensive Care Unit. CHILDREN-BASEL 2018; 5:children5110147. [PMID: 30380730 PMCID: PMC6262526 DOI: 10.3390/children5110147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 10/24/2018] [Accepted: 10/24/2018] [Indexed: 11/26/2022]
Abstract
Introduction: Gamma glutamyl transferase (GGT) and uric acid (UA) are reported to be predictive markers in various disorders. It has been reported that these biomarkers can be used to indicate increased risk of mortality in critically ill patients. Herein, we aimed to evaluate the effects of the initial serum GGT and UA levels on the outcomes of patients in the pediatric intensive care unit (PICU) and to investigate if these biomarkers can be used to predict pediatric mortality. Materials and Methods: The relationship between the initial GGT and UA levels and invasive mechanical ventilation (IMV) and noninvasive mechanical ventilation (NIV) support, inotropic drug need, acute renal kidney injury (AKI), continuous renal replacement therapy (CRRT), presence of sepsis, mortality, and hospitalization period were investigated retrospectively. Results: In all, 236 patients (117 males and 119 females) were included in the study. The age distribution of the patients was 1–12 years. There was a statistically significant relationship between GGT levels in the first biochemical analysis performed during admission and inotropic drug use, AKI, duration of hospitalization in intensive care unit, and sepsis. There was a statistically significant relationship between initial UA levels and inotropic drug use, AKI, CCRT, and sepsis. Conclusion: We suggest that initial GGT and UA levels during admission could be used to predict the outcomes of patients in PICU.
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Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. J Pediatr 2018; 200:181-187. [PMID: 29935878 DOI: 10.1016/j.jpeds.2018.05.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 04/12/2018] [Accepted: 05/05/2018] [Indexed: 01/30/2023]
Abstract
OBJECTIVE To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. STUDY DESIGN Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. RESULTS Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. CONCLUSION Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.
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Development and Validation of Novel Diagnostic Models for Biliary Atresia in a Large Cohort of Chinese Patients. EBioMedicine 2018; 34:223-230. [PMID: 30077722 PMCID: PMC6116426 DOI: 10.1016/j.ebiom.2018.07.025] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 07/06/2018] [Accepted: 07/17/2018] [Indexed: 02/07/2023] Open
Abstract
Background & aims The overlapping features of biliary atresia (BA) and the other forms of neonatal cholestasis (NC) with different causes (non-BA) has posed challenges for the diagnosis of BA. This study aimed at developing new and better diagnostic models for BA. Methods We retrospectively analyzed data from 1728 newborn infants with neonatal obstructive jaundice (NOJ). New prediction models, including decision tree (DT), random forest (RF), and multivariate logistic regression-based nomogram for BA were created and externally validated in an independent set of 508 infant patients. Results Fiver predictors, including gender, weight, direct bilirubin (DB), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT) were significantly different between the BA and non-BA groups (P < .05), from which DT, RF, and nomogram models were developed. The area under the receiver operating characteristic (ROC) curve (AUC) value for the nomogram was 0.898, which was greater than that of a single biomarker in the prediction of BA. Performance comparison of the three diagnostic models showed that the nomogram displayed better discriminative ability (sensitivity, 85.7%; specificity, 80.3%; PPV, 0.969) at the optimal cut-off value compared with DT and RF, which had relatively similar high sensitivity and PPV (0.941 and 0.947, respectively), but low specificity in the modeling group. In sub-analysis of the discriminative capacity between the nomogram and GGT (<300 or ≥ 300), we found that the nomogram was superior to the GGT alone in the preoperative diagnosis of BA. Conclusions The nomogram has demonstrated better performance for the prediction of BA, holding promise for future clinical application.
A novel nomogram has been established for prediction of biliary atresia (BA). Its discriminatory ability is significantly improved compared with GGT alone. It holds promise for clinical application for better diagnosis of BA.
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Correlation between gamma-glutamyl transpeptidase activity and outcomes after Kasai portoenterostomy for biliary atresia. J Pediatr Surg 2018; 53:461-467. [PMID: 29056230 DOI: 10.1016/j.jpedsurg.2017.10.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 09/07/2017] [Accepted: 10/02/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND/PURPOSE The role of serum gamma-glutamyl transpeptidase (GGT) levels in predicting clinical outcomes after Kasai portoenterostomy (KPE) is unknown. This study analyzed whether postoperative GGT along with the aspartate aminotransferase-to-platelet ratio index (APRi) predicted prognosis of biliary atresia (BA). METHODS Data were retrospectively reviewed for 169 BA patients categorized into jaundice-free (JF) (total bilirubin <2.0 mg/dL ≤6 months post-KPE) and persistent jaundice (PJ) groups (total bilirubin ≥2.0 mg/dL ≤6 months post-KPE). Serum biochemical markers, including GGT levels, were measured monthly after KPE, and mean GGT levels and APRi were compared between groups. Factors predicting native liver survival (NLS) were determined using a Cox regression analysis. RESULTS GGT concentrations >550 IU/L at month 5 (hazard ratio: 1.74, P < 0.05), an APRi >0.605 at month 4 (hazard ratio: 3.78, P = 0.001), and being jaundice-free at 6 months (hazard ratio: 5.49, P < 0.001) were independent risk factors for decreased NLS. CONCLUSIONS Serum GGT concentrations >550 IU/L at month 5 and an APRi >0.605 at month 4 post-KPE were associated with significantly lower NLS rates. Among JF patients, those with GGT concentrations >550 IU/L at month 5 and APRi >0.605 at month 4 showed poorer outcomes. TYPE OF STUDY Retrospective comparative study LEVEL OF EVIDENCE: Level III.
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Xiang D, He J, Wang H, Xiong F, Cheng H, Ai J, Shan R, Wan R, Zhang L, Shi J. Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3: A case report. Medicine (Baltimore) 2017; 96:e9158. [PMID: 29390323 PMCID: PMC5815735 DOI: 10.1097/md.0000000000009158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
RATIONALE Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients' first years of age. However, high GGT type PFIC is still rare. PATIENT CONCERNS The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months. He had abdominal tenderness but no rebounding pain. Moreover, his dullness was felt over the liver and the spleen was palpable 8 cm below the ribs. DIAGNOSES Computed tomography and magnetic resonance cholangiopancreato graphy of the upper abdomen revealed cirrhosis, portal hypertension, collateral circulation formation, large spleen, and ascites. Blood biochemistry showed high alanine transaminase, aspartate transaminase, and GGT. The diagnosis of decompensated liver cirrhosis caused by PFIC-3 was finally confirmed by plasma gene detecting. INTERVENTIONS The patient received an open surgery named allogeneic liver transplantation after successful matching of immune types between the recipient and donor. Peritoneal puncture and catheter drainage under B-ultrasound was performed when an encapsulated effusion between the liver and stomach arose. OUTCOMES The patient was discharged without specific discomfort and was almost free of fluid accumulation 51 days after the surgery. At the 6-month follow-up, he had no discomfort and the blood routine, liver functions showed no abnormalities. LESSONS We found a new mutant fragment of ABCB4 gene in the process of diagnosis. Liver transplantation remains the most definitive treatment for PFIC. Current medical therapies and surgical interventions such as biliary diversion have potentially created a synergistic outcome.
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Affiliation(s)
- Deng Xiang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Jiannan He
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Hongmei Wang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Fangfang Xiong
- Basic Nursing Teaching and Research Office, Nanchang City Health School
| | - Hao Cheng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Junhua Ai
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Renfeng Shan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Renhua Wan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Lunli Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jun Shi
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
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Deng M, Mao M, Guo L, Chen FP, Wen WR, Song YZ. Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency. Exp Ther Med 2016; 12:3294-3300. [PMID: 27882152 PMCID: PMC5103782 DOI: 10.3892/etm.2016.3752] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Accepted: 09/06/2016] [Indexed: 12/14/2022] Open
Abstract
The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented. Analysis of the SLC10A1 gene in the patient revealed a homozygous p.Ser267Phe (c.800C>T) variation, which proved to be a single-nucleotide polymorphism (SNP) in the allele frequency of 4.7% of healthy controls. This variation involved a conserved amino acid residue on the orthologous alignment that was predicted to be ‘disease-causing’ by functional analysis using a number of bioinformatic tools. Next generation sequencing was performed; however, no other genetic causes were identified that would affect the bile acid homeostasis in the patient. Moreover, an adult, with the same genotype as the pediatric patient, was identified for the first time as experiencing mild hypercholanemia. The molecular and clinical findings in the present study suggest, for the first time, that there is an association between p.Ser267Phe SNP and hypercholanemia, and this information may be used to clinically identify NTCP deficiency worldwide.
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Affiliation(s)
- Mei Deng
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Man Mao
- Department of Laboratory Science, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Li Guo
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Feng-Ping Chen
- Department of Laboratory Science, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Wang-Rong Wen
- Department of Laboratory Science, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Yuan-Zong Song
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
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Value of Gamma-Glutamyl Transpeptidase for Diagnosis of Biliary Atresia by Correlation With Age. J Pediatr Gastroenterol Nutr 2016; 63:370-3. [PMID: 26963938 DOI: 10.1097/mpg.0000000000001168] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The aim of the study was to analyze the value of gamma-glutamyl transpeptidase (GGT) for distinguishing biliary atresia (BA) from non-BA for patients suspected of having neonatal obstructive jaundice by correlation with age. METHODS From January 2003 to March 2014, cholangiography and/or surgical exploration were undertaken in 1469 patients with suspicion of having neonatal obstructive jaundice. A total of 1338 patients were diagnosed with BA intraoperatively. Preoperative medical records were compared between BA and non-BA patients. RESULTS Preoperative levels of total bilirubin, direct bilirubin, and GGT were significantly higher in the BA group (P < 0.05), whereas the non-BA group had higher alkaline phosphatase levels (P = 0.0003). The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin, GGT, and alkaline phosphatase was 0.584, 0.614, 0.843, and 0.398, respectively. In all age groups (i: 31-60 days; ii: 61-90 days; iii: 91-120 days; iv: ≥121 days), BA groups had higher GGT levels (in IU/L) (i: 725.3 ± 549.9; ii: 927.0 ± 679.8; iii: 1114.3 ± 823.1; iv: 767.5 ± 666.7). The level of GGT in patients with BA younger than 30 days was 834.2 ± 475.3 IU/L. GGT levels had the highest diagnostic value (0.869) in group ii (61-90 days) and the lowest diagnosis value (0.712) in group iv (≥121 days). At a cutoff of >303 IU/L in group ii (61-90 days), GGT had 82.8% sensitivity and 81.6% specificity for the discrimination of BA. CONCLUSIONS GGT levels contribute to the diagnosis of BA before 120 days. Age must be considered if using GGT levels as a diagnostic test for BA.
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Kim DB, Lim G, Oh KW. Determination of reference range of gamma glutamyl transferase in the neonatal intensive care unit. J Matern Fetal Neonatal Med 2016; 30:670-672. [PMID: 27124251 DOI: 10.1080/14767058.2016.1182974] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE We aimed to establish the reference range of gamma glutamyl transferase (GGT) in the first week of life at each gestational age (GA). METHODS This retrospective study included infants born and admitted before 7 days of age with no apparent congenital liver disease during four consecutive years. Early GGT levels measured at 3-7 days of age were analyzed according to GA. Differences according to sex, mode of delivery, small for gestational age, and the predictability for cholestasis were analyzed. RESULTS We analyzed early GGT values in 2091 neonates. The average reference value in neonates (156.7 ± 98.2 IU/L) was much higher than that in adults. The GGT values were significantly higher in preterm than in term infants and in male infants than in female infants. Mode of delivery and small for gestational age were not significantly related to GGT level. Early GGT had no predictive value for cholestasis occurrence. CONCLUSIONS Early GGT levels were much higher in neonates, especially preterm infants with GA of 31-35 weeks.
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Affiliation(s)
- Dong Bin Kim
- a Department of Pediatrics , Ulsan University Hospital, University of Ulsan College of Medicine , Ulsan , South Korea
| | - Gina Lim
- a Department of Pediatrics , Ulsan University Hospital, University of Ulsan College of Medicine , Ulsan , South Korea
| | - Ki Won Oh
- a Department of Pediatrics , Ulsan University Hospital, University of Ulsan College of Medicine , Ulsan , South Korea
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Abstract
The aim of this study was to visually present and discuss in detail the physiological trends of 22 serum biochemistries in children aged 0-18.A data-mining, LMS (lambda, mu, and sigma) approach was employed to derive the smoothed continuous serum biochemistry centile charts, after application of stringent outlier exclusion criteria.Serum sodium and calculated osmolality are low in early life and rise with age due to maturing kidney and body water redistribution. Urea, creatinine and uric acid is high at birth, declines to reach a trough by 1 month of age and gradually rises again thereafter. Serum bicarbonate falls initially during the neonatal and toddler period, then rises with declining respiratory rate, further increasing sodium and suppressing chloride. Potassium, calcium and phosphate are required for somatic growth and are actively accrued during periods of rapid growth. Albumin increases until puberty while globulin rises to age 10 as a result of increased hepatic synthetic capacity and maturing immunity. Serum alkaline phosphatase activity peaks during bone growth spurts in infancy and adolescence due to osteoblast leakage, while creatinine increases with muscle mass. Serum gamma-glutamyl transferase, aspartate aminotransferase and lactate dehydrogenase activities are high at birth and decline with age. Serum alanine aminotransferase activity is low at birth and is induced by increased gluconeogenesis. Serum bilirubin increases continuously with age, mirroring haemoglobin concentration. Serum total cholesterol declines more markedly in boys than girls during puberty due to the combined effects of free testosterone (lowering high-density lipoprotein cholesterol in boys) and oestradiol (lowering low-density lipoprotein cholesterol in boys and girls).It is important to understand trends and biological variation when interpreting results since partitioned reference intervals may mask this information.
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The Features of GGT in Patients with ATP8B1 or ABCB11 Deficiency Improve the Diagnostic Efficiency. PLoS One 2016; 11:e0153114. [PMID: 27050426 PMCID: PMC4822785 DOI: 10.1371/journal.pone.0153114] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 03/23/2016] [Indexed: 01/26/2023] Open
Abstract
Background and Aims Genetic defects in ATP8B1 or ABCB11 account for the majority of cholestasis with low GGT. But the ranges for GGT in patients with ATP8B1 or ABCB11 deficiency are unclear. This study tried to unravel the features of GGT in these patients that improve diagnostic efficiency. Methods This study enrolled 207 patients with chronic cholestasis who were ordered to test for ATP8B1 and/or ABCB11 from January 2012 to December 2015. Additional 17 patients with ATPB81 or ABCB11 deficiency diagnosed between January 2004 and December 2011 were also enrolled in this study. 600 population-matched children served as controls. Clinical data were obtained by retrospectively reviewing medical records. Results A total of 26 patients were diagnosed with ATP8B1 deficiency and 30 patients were diagnosed with ABCB11 deficiency. GGT levels were similar between the two disorders at any observed month of age, but varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year. GGT levels in patients with a genetic diagnosis were different from that in patients without a genetic diagnosis and controls. Larger ranges for GGT were found in patients without a genetic diagnosis. Some controls had GGT≥70U/L in the 2nd~6th month. Of the 207 patients, 39 (18.8%) obtained a genetic diagnosis. 111 patients met the ranges described above, including all the 39 patients with ATP8B1 or ABCB11 deficiency. The sensitivity was 100.0%. The rate of a positive molecular diagnosis increased to 35.1% (39/111 vs. 39/207, X2 = 10.363, P = 0.001). The remaining 96 patients exceeded the ranges described above and failed to receive a genetic diagnosis. These patients accounted for 43.8% of sequencing cost. Conclusions GGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year.
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Fontana RJ. Response to Collyer et al. Am J Gastroenterol 2016; 111:297-8. [PMID: 26882950 DOI: 10.1038/ajg.2015.432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA
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Kobkitjaroen J, Pongprasobchai S, Tientadakul P. γ-Glutamyl Transferase Testing, Change of Its Designation on the Laboratory Request Form, and Resulting Ratio of Inappropriate to Appropriate Use. Lab Med 2015. [DOI: 10.1309/lm7e5lg6pwjyefuj] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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EXP CLIN TRANSPLANTExp Clin Transplant 2015; 13. [DOI: 10.6002/ect.mesot2014.o55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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γ-Glutamyl transpeptidase level as a screening marker among diverse etiologies of infantile intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 2014; 59:695-701. [PMID: 25141230 DOI: 10.1097/mpg.0000000000000538] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Low γ-glutamyl transpeptidase (GGT) level is an important marker for progressive familial intrahepatic cholestasis, yet the cutoff level and clinical application is not well defined. This study aimed to evaluate the role of GGT as a screening marker among diverse etiologies of infantile cholestasis. METHODS This retrospective study analyzed 256 cholestatic infants admitted to a tertiary referral center between 2000 and 2012. After excluding 121 infants of extrahepatic cholestasis, advanced investigations for 135 infants with intrahepatic cholestasis were performed. The etiologies, outcomes, and correlations with GGT levels were analyzed. Good prognosis was defined as clinical recovery before 1 year of age; poor prognosis as persistent disease, liver transplantation, or death before 1 year. RESULTS Among 135 patients of intrahepatic cholestasis, >12 different etiologies were found. Neonatal hepatitis (49.6%), progressive familial intrahepatic cholestasis (21.5%), and neonatal cholestasis caused by citrin deficiency (10.4%) were the leading causes. Patients with initial GGT between 75 and 300 U/L had a higher chance of good prognosis (61/74, 82.4%) than those with GGT <75 U/L or >300 U/L (25/61, 41%, P < 0.0001). In the low-GGT group (≤ 100 U/L), 52.6% (30/57) of the patients have good prognosis; and GGT level ≤ 75 U/L has a sensitivity, specificity, and positive predictive value of 100%, 43.3%, and 61.4% in predicting poor prognosis. CONCLUSIONS Patients with GGT levels ≤ 75 or ≥ 300 U/L should receive advanced investigations such as genetic/metabolic assays early; otherwise, the amount of diagnostic workup may be limited if no signs of progressive disease.
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Poddighe D, Castelli L, Marseglia GL, Bruni P. Prolonged, but transient, elevation of liver and biliary function tests in a healthy infant affected with breast milk jaundice. BMJ Case Rep 2014; 2014:bcr2014204124. [PMID: 24872488 PMCID: PMC4039948 DOI: 10.1136/bcr-2014-204124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/08/2014] [Indexed: 11/04/2022] Open
Abstract
Unconjugated hyperbilirubinaemia is a common finding in newborns. When it is exaggerated, it is usually investigated in order to exclude several diseases, such as newborn's haemolytic diseases, infections or hypothyroidism. Breast milk jaundice is a form of neonatal jaundice related to breast feeding and it is not usually associated with any clinical issue and/or other laboratory abnormalities. We describe a case of breast milk jaundice being associated, unexpectedly, to significant elevation of plasmatic liver and biliary enzymes. Despite the infant's good clinical condition and growth, several investigations were performed and these ruled out metabolic, infectious and autoimmune liver diseases. All liver function tests normalised by 6-7 months of life. We suggest that the finding of hypertransaminasaemia and hyper-γ-glutamyl transpeptidase in a benign clinical context (similar to what we described) should be followed for 6-7 months before performing sophisticated and expensive diagnostic investigations which aim at excluding some unlikely and severe diseases in a completely asymptomatic infant.
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Affiliation(s)
- Dimitri Poddighe
- Department of Pediatrics, Ospedale di Circolo di Melegnano, Vizzolo Predabissi, Italy
| | - Lucia Castelli
- Department of Pediatrics, Ospedale di Circolo di Melegnano, Vizzolo Predabissi, Italy
| | | | - Paola Bruni
- Department of Pediatrics, Ospedale di Circolo di Melegnano, Vizzolo Predabissi, Italy
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Abstract
OBJECTIVES Gamma-glutamyl transferase (GGT) is commonly measured in newborn infants as a sensitive liver function test; however, reference ranges are mostly based on early studies, including relatively small number of patients. The aim of this study was to emphasise recently changed GGT values because of changed newborns profile admitted to neonatal intensive care units (NICUs) and establish new cross-sectional reference ranges for the serum GGT levels in a cohort of neonates between 26 and 42 weeks' gestational age in 1 centre. METHODS From January 1, 2010 to December 31, 2012, liver function tests including serum GGT measurements were performed in 705 newborns who were admitted to NICUs because of different aetiologies at Gazi University School of Medicine Hospital, Ankara, Turkey. Infants with Apgar score <8 at the fifth minute, any metabolic or liver disease, cholestasis, congenital infection, culture-proven sepsis, elevated serum aminotransferases, and who were treated with phenobarbital were excluded. Clinical and laboratory data of 583 neonates were analysed retrospectively. GGT was measured by enzymatic method using the Abbott Architect C16000 autoanalyser. Mean, 2.5th, and 97.5th percentiles were used to express the reference range data. RESULTS Four hundred sixty-one GGT values of 200 preterm infants and 501 GGT values of 383 term infants during the first 28 days after birth were analysed. Serum GGT levels of preterm infants in the first 7 days and between 8 and 28 days after delivery were (mean±standard deviation; 141.81±88.56 U/L and 131.17±85.53 U/L) similar to term infants (139.90±86.46 U/L and 144.56±86.51 U/L), respectively (P=0.649 and P=0.087). Serum GGT levels were found to be significantly higher in male infants (no need of query) (145.98±93.68 U/L) than female infants (132.18±78.97 U/L) (P=0.035), and infants born vaginally (152.24±90.71 U/L) also had higher serum GGT activity than those born by caesarean section (135.38±85.37 U/L) (P=0.005). CONCLUSIONS A new reference range for serum GGT levels that is higher than previous reference values can identify neonates with truly abnormal results and prevent unnecessary interventions.
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