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1
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Zhao H, Tian X, Wu B, Lu Y, Du J, Peng S, Xiao Y. Neurotensin contributes to cholestatic liver disease potentially modulating matrix metalloprotease-7. Int J Biochem Cell Biol 2024; 170:106567. [PMID: 38522506 DOI: 10.1016/j.biocel.2024.106567] [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: 12/21/2023] [Revised: 02/27/2024] [Accepted: 03/19/2024] [Indexed: 03/26/2024]
Abstract
The diagnosis and treatment of biliary atresia pose challenges due to the absence of reliable biomarkers and limited understanding of its etiology. The plasma and liver of patients with biliary atresia exhibit elevated levels of neurotensin. To investigate the specific role of neurotensin in the progression of biliary atresia, the patient's liver pathological section was employed. Biliary organoids, cultured biliary cells, and a mouse model were employed to elucidate both the potential diagnostic significance of neurotensin and its underlying mechanistic pathway. In patients' blood, the levels of neurotensin were positively correlated with matrix metalloprotease-7, interleukin-8, and liver function enzymes. Neurotensin and neurotensin receptors were mainly expressed in the intrahepatic biliary cells and were stimulated by bile acids. Neurotensin suppressed the growth and increased expression of matrix metalloprotease-7 in biliary organoids. Neurotensin inhibited mitochondrial respiration, oxidative phosphorylation, and attenuated the activation of calmodulin-dependent kinase kinase 2-adenosine monophosphate-activated protein kinase (CaMKK2-AMPK) signaling in cultured biliary cells. The stimulation of neurotensin in mice and cultured cholangiocytes resulted in the upregulation of matrix metalloprotease-7 expression through binding to its receptors, namely neurotensin receptors 1/3, thereby attenuating the activation of the CaMKK2-AMPK pathway. In conclusion, these findings revealed the changes of neurotensin in patients with cholestatic liver disease and its mechanism in the progression of the disease, providing a new understanding of the complex mechanism of hepatobiliary injury in children with biliary atresia.
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Affiliation(s)
- Hongxia Zhao
- Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Xinbei Tian
- Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Bo Wu
- Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Lu
- Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Jun Du
- Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Shicheng Peng
- Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yongtao Xiao
- Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
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2
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El Raichani N, Thibault M, Alvarez F, Lavoie JC, Mohamed I. The effects of gestational age on neonatal cholestasis: A retrospective cohort study. J Neonatal Perinatal Med 2024; 17:101-110. [PMID: 38251066 DOI: 10.3233/npm-230034] [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: 01/23/2024]
Abstract
BACKGROUND Reference guidelines for neonatal conjugated hyperbilirubinemia (cholestasis) management use a uniform approach regardless of gestational age (GA). We hypothesize that the clinical pattern of neonatal cholestasis is tightly related to GA. The aim of this study was to describe the effects of GA on neonatal cholestasis. METHODS A retrospective 4-year cohort study in a 70-bed neonatal care unit. Neonates with conjugated bilirubin≥34.2μmol/L (2 mg/dL) were identified. The incidence, clinical characteristics, etiology, treatment, and prognosis were compared between infants <32 and≥32 weeks GA. RESULTS Overall incidence of cholestasis was 4% (125/3402). It was >5 times higher and the mean duration was >1.5 times longer in neonates <32 weeks GA (10% versus 1.8%, p <0.01 and 49 versus 31 days, p <0.01, respectively). The onset of cholestasis was later in neonates <32 weeks (22 versus 10 days of life, p <0.001). This later onset of cholestasis was associated with parenteral nutrition, whereas the earlier onset was associated with other causes. Treatment using fish oil lipids was more frequently administrated to infants <32 weeks GA, whereas Ursodeoxycholic acid was administrated more frequently in≥32 weeks GA. Cholestasis resolved during hospitalization in 73% of <32 versus 38% in≥32 weeks GA infants (p <0.01). CONCLUSIONS The incidence, clinical presentation, etiology, treatment, and clinical evolution of neonatal cholestasis were all significantly affected by GA. Our results support the use of a GA-oriented approach for the management of neonatal cholestasis.
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Affiliation(s)
- N El Raichani
- Department of Nutrition, University of Montreal, Montreal, QC, Canada
| | - M Thibault
- Department of Pharmacy, CHU Sainte-Justine, Montreal, QC, Canada
| | - F Alvarez
- Department of Pediatrics-Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada
| | - J-C Lavoie
- Department of Nutrition, University of Montreal, Montreal, QC, Canada
- Departments of Pediatrics-Neonatology, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada
| | - I Mohamed
- Department of Nutrition, University of Montreal, Montreal, QC, Canada
- Departments of Pediatrics-Neonatology, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada
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3
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Schmidt HC, Hagens J, Schuppert P, Appl B, Raluy LP, Trochimiuk M, Philippi C, Li Z, Reinshagen K, Tomuschat C. Biliatresone induces cholangiopathy in C57BL/6J neonates. Sci Rep 2023; 13:10574. [PMID: 37386088 PMCID: PMC10310722 DOI: 10.1038/s41598-023-37354-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 06/20/2023] [Indexed: 07/01/2023] Open
Abstract
Exposure to plant toxins or microbiota that are able to digest common food ingredients to toxic structures might be responsible for biliary atresia (BA). An isoflavonoid, biliatresone is known to effectively alter the extrahepatic bile duct (EHBD) development in BALB/c mice. Biliatresone causes a reduction of Glutathione (GSH) levels, SOX17 downregulation and is effectively countered with N-Acetyl-L-cysteine treatment in vitro. Therefore, reversing GSH-loss appears to be a promising treatment target for a translational approach. Since BALB/c mice have been described as sensitive in various models, we evaluated the toxic effect of biliatresone in robust C57BL/6J mice and confirmed its toxicity. Comparison between BALB/c and C57BL/6J mice revealed similarity in the toxic model. Affected neonates exhibited clinical symptoms of BA, such as jaundice, ascites, clay-colored stools, yellow urine and impaired weight gain. The gallbladders of jaundiced neonates were hydropic and EHBD were twisted and enlarged. Serum and histological analysis proved cholestasis. No anomalies were seen in the liver and EHBD of control animals. With our study we join a chain of evidence confirming that biliatresone is an effective agent for cross-lineage targeted alteration of the EHBD system.
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Affiliation(s)
- Hans Christian Schmidt
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Johanna Hagens
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Pauline Schuppert
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Birgit Appl
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Laia Pagerols Raluy
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Magdalena Trochimiuk
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Clara Philippi
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Zhongwen Li
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Konrad Reinshagen
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Christian Tomuschat
- Research Laboratory W23, Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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4
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Gautam AD, Yadav RR, Sarma MS, Mandelia A, Agrawal V, Lal R, Gupta A. Shear Wave Elastography: A Reliable Secondary Parameter for Diagnosing Biliary Atresia in Infants With Neonatal Cholestasis. Cureus 2023; 15:e37911. [PMID: 37122975 PMCID: PMC10136369 DOI: 10.7759/cureus.37911] [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: 04/18/2023] [Indexed: 05/02/2023] Open
Abstract
Objective In this study, we aimed to optimize various grayscale, Doppler, and elastography parameters and evaluate their diagnostic performance in the preoperative diagnosis of biliary atresia (BA). Materials and methods A total of 158 infants aged <6 months with neonatal cholestasis (NC) were enrolled in the study and sonography was performed after four hours of fasting. For comparison of elastography, 31 exclusively age-matched controls, not suffering from liver disease, were included separately. Triangular cord and gallbladder (GB) parameters were considered as primary parameters, while right hepatic artery (RHA) caliber, RHA-to-right portal vein (RPV) ratio, hepatic subcapsular flow (HSF), and shear wave elastography (SWE) were considered as secondary parameters. Diagnosis of infants with BA was confirmed on histopathology. Data were presented as mean ±standard deviation (SD) and frequency. Differences between groups were compared using the Chi-square test and the unpaired student t-test. Receiver operating characteristic (ROC) curve analysis was done for individual ultrasound/Doppler/SWE parameters to calculate the optimal cutoff value. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for each parameter and their combinations. Results Of the primary parameters, GB contractility index (CI) and length showed the highest sensitivity and specificity respectively. A cutoff of 14 kPA was derived for SWE for the diagnosis of BA. Among secondary parameters, SWE had the best diagnostic performance, better than even the individual primary parameters. A combination of primary parameters with SWE in series showed the highest accuracy. Conclusion Among secondary parameters, elastography can prove to be highly useful. The highest accuracy in diagnosing BA can be obtained by combining primary parameters with SWE.
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Affiliation(s)
- Avinash D Gautam
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Rajanikant R Yadav
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Moinak S Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Ankur Mandelia
- Department of Pediatric Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Vinita Agrawal
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Richa Lal
- Department of Pediatric Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Archna Gupta
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
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5
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Roggero P, Liotto N, Piemontese P, Menis C, Perrone M, Tabasso C, Amato O, Orsi A, Pesenti N, Leva E, Mosca F. Neonatal intestinal failure: Growth pattern and nutrition intakes in accordance with weaning from parenteral nutrition. JPEN J Parenter Enteral Nutr 2023; 47:236-244. [PMID: 36398420 DOI: 10.1002/jpen.2465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/08/2022] [Accepted: 11/13/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF. METHODS Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning. RESULTS We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P < 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039). CONCLUSION Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.
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Affiliation(s)
- Paola Roggero
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Nadia Liotto
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Pasqua Piemontese
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Camilla Menis
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Michela Perrone
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Chiara Tabasso
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Orsola Amato
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Anna Orsi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
| | - Nicola Pesenti
- Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Ernesto Leva
- Department of Pediatric Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Clinical Science and Community Health, University of Milan, Milan, Italy
| | - Fabio Mosca
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy.,Department of Clinical Science and Community Health, University of Milan, Milan, Italy
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6
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Moutinho TJ, Powers DA, Hanson GF, Levy S, Baveja R, Hefner I, Mohamed M, Abdelghani A, Baker RL, Papin JA, Moore SR, Hourigan SK. Fecal sphingolipids predict parenteral nutrition-associated cholestasis in the neonatal intensive care unit. JPEN J Parenter Enteral Nutr 2022; 46:1903-1913. [PMID: 35285019 PMCID: PMC9468188 DOI: 10.1002/jpen.2374] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/23/2022] [Accepted: 03/06/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Parenteral nutrition-associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data, would better predict risk for developing PNAC. METHODS Using untargeted metabolomics in 200 serial stool samples from 60 infants, we applied statistical and machine learning approaches to identify clinical features and metabolic biomarkers with the greatest associative potential for risk of developing PNAC. Stools were collected prospectively from infants receiving PN with soybean oil-based lipid emulsion at a level IV NICU. RESULTS Low birth weight, extreme prematurity, longer duration of PN, and greater number of antibiotic courses were all risk factors for PNAC (P < 0.05). We identified 78 stool biomarkers with early predictive potential (P < 0.05). From these 78 biomarkers, we further identified 12 sphingomyelin lipids with high association for the development of PNAC in precholestasis stool samples when combined with birth anthropometry. CONCLUSION We demonstrate the potential for stool metabolomics to enhance early identification of PNAC risk. Earlier detection of high-risk infants would empower proactive mitigation with alterations to PN for at-risk infants and optimization of energy nutrition with PN for infants at lower risk.
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Affiliation(s)
- Thomas J. Moutinho
- Department of Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Deborah A. Powers
- Department of Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Gabriel F. Hanson
- Department of Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Shira Levy
- Inova Children's HospitalFalls ChurchVirginiaUSA
| | - Rajiv Baveja
- Fairfax Neonatal AssociatesFalls ChurchVirginiaUSA
| | | | | | | | | | - Jason A. Papin
- Department of Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Sean R. Moore
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of PediatricsUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Suchitra K. Hourigan
- Inova Children's HospitalFalls ChurchVirginiaUSA,Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of PediatricsUniversity of VirginiaCharlottesvilleVirginiaUSA,Division of Pediatric GastroenterologyPediatric Specialists of VirginiaFairfaxVirginiaUSA,Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMarylandUSA
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7
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Watchko JF, Maisels MJ. Management of severe hyperbilirubinemia in the cholestatic neonate: a review and an approach. J Perinatol 2022; 42:695-701. [PMID: 35145210 DOI: 10.1038/s41372-022-01330-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 01/13/2022] [Accepted: 01/26/2022] [Indexed: 12/11/2022]
Abstract
A review of the literature demonstrates that severe total hyperbilirubinemia (total serum bilirubin ≥ 20 mg/dL [340 µmol/L]) in some cholestatic term (≥37 weeks) and late-preterm (≥340/7-366/7 weeks) gestation neonates poses a risk for bilirubin-induced brain damage. When the direct bilirubin fraction is <50% of the total serum bilirubin this risk is associated with the total serum bilirubin alone and treatment decisions should be based on the total serum bilirubin. On the other hand, there are limited data on the risk of bilirubin-induced brain damage in the neonate with severe total hyperbilirubinemia and a direct bilirubin fraction that is equal to or exceeds 50% of the total serum bilirubin. When this rare combination occurs, efforts to keep the indirect bilirubin fraction from reaching severe levels might, nevertheless, be prudent.
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Affiliation(s)
- Jon F Watchko
- Professor Emeritus Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
| | - M Jeffrey Maisels
- Department of Pediatrics, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.,Department of Pediatrics, Beaumont Children's Hospital, Royal Oak, MI, USA
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Chan WK, Chung PHY, Wong KKY. The Value of Hepatic Scintigraphy in the Diagnosis of Biliary Atresia. Front Pediatr 2022; 10:874809. [PMID: 35712619 PMCID: PMC9194445 DOI: 10.3389/fped.2022.874809] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 05/16/2022] [Indexed: 11/14/2022] Open
Abstract
Introduction Biliary Atresia (BA) requires prompt diagnosis and surgical intervention to optimize its outcome. The aim of this study was to evaluate the accuracy of EHIDA in distinguishing between BA and other causes of cholestatic jaundice. Methods This was a retrospective study of all patients who underwent EHIDA in a tertiary center from 1997 to 2019. The sensitivity, specificity, Negative Predictive Value (NPV) and Positive Predictive Value (PPV) of EHIDA were evaluated. Factors that can potentially affect its accuracy were also analyzed. Results During the study period, 93 patients aged 10 to 110 days with cholestasis and suspected BA underwent EHIDA. The sensitivity and NPV were 91.2 and 85.3% while specificity and PPV were 80.6 and 88.1%. These results suggested that EHIDA is suboptimal in both diagnosing or excluding BA. Out of 59 patients who showed no tracer activities in the intestines after 24 h, 56 were subjected to surgical exploration and 52 (92.9%) were eventually diagnosed BA. The accuracy of EHIDA scan were different by the maturity of the patient, age at testing and severity of cholestasis. Conclusions EHIDA has a limited accuracy and surgical exploration remains the gold standard to establish the diagnosis of BA. Potential confounding factors that may affect the accuracy of EHIDA were identified but require further studies with larger sample sizes to validate.
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Affiliation(s)
- Wing Ki Chan
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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9
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Mahmud S, Gulshan J, Parvez M, Tasneem F, Ahmed SS. Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-021-00168-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh.
Results
Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes.
Conclusion
BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.
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10
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Ringoringo HP. The Role of Ursodeoxycholic Acid and Phenobarbital in a Child with Cholestasis: A Longitudinal Study. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.7735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Cholestasis is a condition that starts in the 1st months of life and progresses with direct (conjugated) bilirubin increase and jaundice as a result of impaired bile production or excretion. Its incidence is known as 1 in 2500 live births. This study shows the effectiveness of ursodeoxycholic acid (UDCA) and phenobarbital in infant cholestasis treatment.
CASE REPORT: A 28-days-old boy came with a complaint of yellow eyes. At the age of 3 days, the patient looked yellow, had a fever and difficulty drinking, received phototherapy. After 2 weeks of treatment with neonatal sepsis, the patient was discharged in a stable. The skin appears yellow. The laboratory results show anemia, elevated conjugated bilirubin, and signs of infection; the abdominal ultrasonography shows that the liver and gallbladder were normal. The diagnosis is cholestasis due to sepsis. After 3 months of treatment with UDCA and phenobarbital, jaundiced disappeared, and liver function tests were normal. When the patient is 2 ½ years old, the growth and development suit his age.
CONCLUSION: Early diagnosis and timely treatment of UDCA and phenobarbital play a role in cholestasis improvement. On long-term observation, the child’s growth and development are suitable according to his age and average laboratory results.
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11
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Mintjens S, Lala R, Pollack R. Neonatal Hyperbilirubinemia and Cholestasis. Neoreviews 2021; 22:e622-e626. [PMID: 34470765 DOI: 10.1542/neo.22-9-e622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Affiliation(s)
- Stijn Mintjens
- Division of Neonatology, Department of Pediatrics, NYC Health and Hospitals, Lincoln Hospital-Weill Cornell Medical Center, Bronx, NY
| | - Rasila Lala
- Division of Neonatology, Department of Pediatrics, NYC Health and Hospitals, Lincoln Hospital-Weill Cornell Medical Center, Bronx, NY
| | - Rebecca Pollack
- Division of Neonatology, Department of Pediatrics, NYC Health and Hospitals, Lincoln Hospital-Weill Cornell Medical Center, Bronx, NY
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12
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Tessitore M, Sorrentino E, Schiano Di Cola G, Colucci A, Vajro P, Mandato C. Malnutrition in Pediatric Chronic Cholestatic Disease: An Up-to-Date Overview. Nutrients 2021; 13:2785. [PMID: 34444944 PMCID: PMC8400766 DOI: 10.3390/nu13082785] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/08/2021] [Accepted: 08/11/2021] [Indexed: 12/16/2022] Open
Abstract
Despite recent advances, the causes of and effective therapies for pediatric chronic cholestatic diseases remain elusive, and many patients progress to liver failure and need liver transplantation. Malnutrition is a common complication in these patients and is a well-recognized, tremendous challenge for the clinician. We undertook a narrative review of both recent and relevant older literature, published during the last 20 years, for studies linking nutrition to pediatric chronic cholestasis. The collected data confirm that malnutrition and failure to thrive are associated with increased risks of morbidity and mortality, and they also affect the outcomes of liver transplantation, including long-term survival. Malnutrition in children with chronic liver disease is multifactorial and with multiple potential nutritional deficiencies. To improve life expectancy and the quality of life, patients require careful assessments and appropriate management of their nutritional statuses by multidisciplinary teams, which can identify and/or prevent specific deficiencies and initiate appropriate interventions. Solutions available for the clinical management of these children in general, as well as those directed to specific etiologies, are summarized. We particularly focus on fat-soluble vitamin deficiency and malnutrition due to fat malabsorption. Supplemental feeding, including medium-chain triglycerides, essential fatty acids, branched-chain amino acids, and the extra calories needed to overcome the consequences of anorexia and high energy requirements, is reviewed. Future studies should address the need for further improving commercially available and nutritionally complete infant milk formulae for the dietary management of this fragile category of patients. The aid of a specialist dietitian, educational training regarding nutritional guidelines for stakeholders, and improving family nutritional health literacy appear essential.
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Affiliation(s)
- Maria Tessitore
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Chair of Pediatrics and Residency Program of Pediatrics, Via S. Allende, University of Salerno, 84081 Baronissi, SA, Italy; (M.T.); (E.S.); (G.S.D.C.); (A.C.); (P.V.)
| | - Eduardo Sorrentino
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Chair of Pediatrics and Residency Program of Pediatrics, Via S. Allende, University of Salerno, 84081 Baronissi, SA, Italy; (M.T.); (E.S.); (G.S.D.C.); (A.C.); (P.V.)
| | - Giuseppe Schiano Di Cola
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Chair of Pediatrics and Residency Program of Pediatrics, Via S. Allende, University of Salerno, 84081 Baronissi, SA, Italy; (M.T.); (E.S.); (G.S.D.C.); (A.C.); (P.V.)
| | - Angelo Colucci
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Chair of Pediatrics and Residency Program of Pediatrics, Via S. Allende, University of Salerno, 84081 Baronissi, SA, Italy; (M.T.); (E.S.); (G.S.D.C.); (A.C.); (P.V.)
| | - Pietro Vajro
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, Chair of Pediatrics and Residency Program of Pediatrics, Via S. Allende, University of Salerno, 84081 Baronissi, SA, Italy; (M.T.); (E.S.); (G.S.D.C.); (A.C.); (P.V.)
| | - Claudia Mandato
- Department of Pediatrics, Santobono-Pausilipon Children’s Hospital Via M. Fiore, 80129 Naples, Italy
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Ling DXH, Bolisetty S, Krishnan U. Cholestatic jaundice in neonates: How common is biliary atresia? Experience at an Australian tertiary centre. J Paediatr Child Health 2021; 57:87-95. [PMID: 32808395 DOI: 10.1111/jpc.15131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 07/17/2020] [Accepted: 07/26/2020] [Indexed: 11/27/2022]
Abstract
AIM To (i) review the aetiologies of neonatal cholestasis among term and preterm neonates at a single tertiary centre in Australia; (ii) identify clinical variables associated with biliary atresia (BA) and non-BA aetiology of neonatal cholestasis; (iii) investigate the utility of hepatobiliary scintigraphy in predicting BA among term and preterm neonates. METHODS A retrospective cohort study of neonates born and investigated for cholestasis at two co-located neonatal and children facilities from January 2013 to December 2017. RESULTS Of the 139 neonates with cholestasis, BA and intestinal-failure-associated liver-disease was the most common cause of neonatal cholestasis in term (18%) and preterm (66%) cohorts, respectively. Incidence of BA was higher in term (1:6) than preterm (1:50) neonates (OR 10.29; 95% CI 2.06-49.97, P = 0.0024). Higher birthweight, acholic stool, absent or abnormal gallbladder on ultrasound was significantly associated with BA while gestational age ≤32 weeks, total parenteral nutrition ≥14 days and low albumin were associated with non-BA aetiology of cholestasis. In diagnosing BA, non-draining hepatobiliary scintigraphy demonstrated a lower specificity (73% vs. 90%) and lower positive predictive value (25% vs. 78%) in preterm compared to term neonates. CONCLUSION Aetiology of cholestasis among preterm neonates differs from those in term neonates and currently existing diagnostic algorithm for neonatal cholestasis may need to be modified for preterm cohort, taking into account the prevalence for each aetiology, potential predictors and cost-efficiency.
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Affiliation(s)
- David X H Ling
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Srinivas Bolisetty
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,Department of Newborn Care, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Usha Krishnan
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,Department of Gastroenterology, Sydney Children Hospital, Sydney, New South Wales, Australia
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Hansen TWR, Wong RJ, Stevenson DK. Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn. Physiol Rev 2020; 100:1291-1346. [PMID: 32401177 DOI: 10.1152/physrev.00004.2019] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.
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Affiliation(s)
- Thor W R Hansen
- Division of Paediatric and Adolescent Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; and Department of Pediatrics, Stanford University School of Medicine, Stanford, California
| | - Ronald J Wong
- Division of Paediatric and Adolescent Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; and Department of Pediatrics, Stanford University School of Medicine, Stanford, California
| | - David K Stevenson
- Division of Paediatric and Adolescent Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; and Department of Pediatrics, Stanford University School of Medicine, Stanford, California
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Iwatani S, Kataoka D, Tamaki S, Yokota T, Yoshimoto S. High prevalence of cholestasis at a tertiary neonatal intensive care unit. Pediatr Int 2020; 62:749-751. [PMID: 32478458 DOI: 10.1111/ped.14180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 01/15/2020] [Accepted: 01/31/2020] [Indexed: 11/27/2022]
Affiliation(s)
- Sota Iwatani
- Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Kobe, Hyogo, Japan
| | - Dai Kataoka
- Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Kobe, Hyogo, Japan
| | - Shoko Tamaki
- Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Kobe, Hyogo, Japan
| | - Tomoyuki Yokota
- Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Kobe, Hyogo, Japan
| | - Seiji Yoshimoto
- Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Kobe, Hyogo, Japan
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Ghazy RM, Khedr MA. Neonatal cholestasis: recent insights. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2019. [DOI: 10.1186/s43054-019-0009-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
AbstractBackgroundNeonatal physiological jaundice is a common benign condition that rarely extends behind the second week of life; however, it may interfere with the diagnosis of a pathological condition termed neonatal cholestasis (NC). The latter is a critical, uncommon problem characterized by conjugated hyperbilirubinaemia. This review aims to highlight the differences between physiological and pathological jaundice, identify different causes of NC, and provide a recent approach to diagnosis and management of this serious condition.Main textNC affects 1/2500 live births, resulting in life-threatening complications due to associated hepatobiliary or metabolic abnormalities. NC is rarely benign and indicates the presence of severe underlying disease. If jaundice extends more than 14 days in full-term infants or 21 days in preterm infants, the serum bilirubin level fractionated into conjugated (direct) and unconjugated (indirect) bilirubin should be measured. A stepwise diagnostic approach starts with obtaining a complete history, and a physical examination which are valuable for the rapid diagnosis of the underlying disease. The most frequently diagnosed causes of NC are biliary atresia (BA) and idiopathic neonatal hepatitis (INH). The early diagnosis of NC ensures more accurate management and better prognosis. Despite the unavailability of any specific treatments for some causes of NC, the patient can benefit from nutritional management and early medical intervention. Future research should attempt to shed light on methods of screening for NC, especially for causes that can be effectively treated either through proper nutritional support, appropriate chemotherapeutic management, or timely surgical intervention.ConclusionFurther attention should be paid for diagnosis and treatment of NC as it may be misdiagnosed as physiological jaundice; this may delay the proper management of the underlying diseases and aggravates its complications.
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Gunaydin M, Tugce Bozkurter Cil A. Cholestasis in the Baby and Infant. EUROPEAN MEDICAL JOURNAL 2019. [DOI: 10.33590/emj/10310839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Cholestasis in children is a serious condition due to various aetiologic factors. If children with jaundice present with acholic stool, dark urine colour, or direct hyperbilirubinaemia, the patient should be evaluated urgently. Early and timely diagnosis and initiation of appropriate treatment are extremely important determinants of morbidity and mortality. In the neonatal period, idiopathic neonatal cholestasis, alpha-1 antitrypsin deficiency, cholestasis from infections, and biliary atresia are the most common causes of cholestasis. Nowadays, with the development of genetic and molecular biological studies, the diagnosis of many diseases that have previously been evaluated as ‘idiopathic‘ can be made. It is the aetiological factor that determines the prognosis. The treatment plan is created in accordance with aetiological causes and in response to symptoms such as pruritus and malabsorption: this can be surgical treatment across a diverse spectrum, from biliary diversion to liver transplantation. In this study, the aetiology, diagnosis, and treatment of cholestasis in babies and infants are reviewed in the light of current literature.
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Affiliation(s)
- Mithat Gunaydin
- Avicenna Hospital, Department of Pediatric Surgery, Istanbul, Turkey
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Pandita A, Gupta V, Gupta G. Neonatal Cholestasis: A Pandora's Box. CLINICAL MEDICINE INSIGHTS-PEDIATRICS 2018; 12:1179556518805412. [PMID: 30574003 PMCID: PMC6295748 DOI: 10.1177/1179556518805412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 08/29/2018] [Indexed: 12/15/2022]
Abstract
Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition–associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.
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Affiliation(s)
- Aakash Pandita
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vishal Gupta
- Department of Neonatology, Max Hospital, New Delhi, India
| | - Girish Gupta
- Department of Neonatology, Max Hospital, New Delhi, India
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Huang YH, Shih HH, Tiao MM, Huang CC, Kuo KC, Huang FC, Yang YL, Chuang JH. Toll-like receptor 7 agonist induces hypoplasia of the biliary system in a neonatal mouse model. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2018; 51:166-173. [PMID: 27590984 DOI: 10.1016/j.jmii.2016.07.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 06/06/2016] [Accepted: 07/18/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND/PURPOSE Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated. METHODS TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day. Morphological and histological injuries of liver and gallbladder were examined at 2 weeks. Hepatic messenger RNA expression of TLR7 signaling was studied. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling staining was used to delineate hepatobiliary apoptosis upon TLR7 stimulation. RESULTS TLR7 agonist, imiquimod, induced hypoplasia of the biliary system of neonatal Balb/c mice both in atrophic gallbladder and in paucity of intrahepatic bile ducts. There was significantly higher hepatic expression of TLR7 and downstream innate immunity-mediated interferon regulatory factor 7, interferon-α, and tumor necrosis factor-α. In addition, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells in the liver were increased after injections of TLR7 agonist. CONCLUSION The results demonstrate that TLR7 activation may trigger innate immunity pathways and induce apoptosis and hypoplasia of neonatal biliary trees in Balb/c mice. The novel findings give an implication of pathogenesis of infantile cholestasis, such as BA.
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Affiliation(s)
- Ying-Hsien Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Hsiang-Hung Shih
- Graduate Institute of Clinical Medicine Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mao-Meng Tiao
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chao-Cheng Huang
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Kuang-Che Kuo
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Fu-Chen Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ya-Ling Yang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jiin-Haur Chuang
- Graduate Institute of Clinical Medicine Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
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Freeman AJ, Hofmekler T, Berauer JP, Palle S. Update in Pediatric Gastroenterology, Hepatology and Nutrition. UPDATE IN PEDIATRICS 2018:267-311. [DOI: 10.1007/978-3-319-58027-2_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
Due to a peculiar age-dependent increased susceptibility, neonatal cholestasis affects the liver of approximately 1 in every 2500 term infants. A high index of suspicion is the key to an early diagnosis, and to implement timely, often life-saving treatments. Even when specific treatment is not available or curative, prompt medical management and optimization of nutrition are of paramount importance to survival and avoidance of complications. Areas covered: The present article will prominently focus on a series of newer diagnostic and therapeutic options of cholestasis in neonates and infants blended with consolidated established paradigms. The overview of strategies for the management reported here is based on a systematic literature search published in English using accessible databases (PubMed, MEDLINE) with the keywords biliary atresia, choleretics and neonatal cholestasis. References lists from retrieved articles were also reviewed. Expert commentary: A large number of uncommon and rare hepatobiliary disorders may present with cholestasis during the neonatal and infantile period. Potentially life-saving disease-specific pharmacological and surgical therapeutic approaches are currently available. Advances in hepatobiliary transport mechanisms have started clarifying fundamental aspects of inherited and acquired cholestasis, laying the foundation for the development of possibly more effective specific therapies.
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Affiliation(s)
- Andrea Catzola
- a Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Pediatrics Section , University of Salerno , Salerno , Italy
| | - Pietro Vajro
- a Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Pediatrics Section , University of Salerno , Salerno , Italy
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Abstract
Jaundice is a key manifestation of hepatobiliary disease in all age groups. Jaundice is a common finding in the first 2 weeks after birth, occurring in 2.4% to 15% of newborns. The neonatal liver is at increased susceptibility to cholestasis, with an incidence ranging from 1 in 2,500 to 1 in 5,000 live births. Etiologies vary, but the most common is biliary atresia. In 2004, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition published guidelines for the evaluation of cholestasis that clearly stated any infant with jaundice persisting beyond age 2 weeks (3 weeks in breast-fed infants with an otherwise normal history and physical examination) should be evaluated with a fractionated serum bilirubin level. Prompt evaluation, diagnosis, and intervention are vital to optimize timely intervention and improve clinical outcomes. This article discusses the etiology, diagnosis and evaluation of cholestatis in infants. [Pediatr Ann. 2016;45(12):e414-e419.].
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Gottesman LE, Del Vecchio MT, Aronoff SC. Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects. BMC Pediatr 2015; 15:192. [PMID: 26589959 PMCID: PMC4654877 DOI: 10.1186/s12887-015-0506-5] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 11/14/2015] [Indexed: 12/28/2022] Open
Abstract
Background The etiologies of conjugated hyperbilirubinemia in infancy are diverse. Objective Determine the prevalence rates of the specific etiologies of conjugated hyperbilirubinemia in infancy. Data sources EMBASE and Pubmed were searched electronically and the bibliographies of selected studies were search manually. The search was conducted independently by two authors. Study selection (1) prospective or retrospective case series or cohort study with 10 or more subjects; (2) consecutive infants who presented with conjugated hyperbilirubinemia; (3) subjects underwent appropriate diagnostic work-up for conjugated hyperbilirubinemia; (4) no specific diagnoses were excluded in the studied cohort. Data extraction Patient number, age range, country of origin, and categorical and specific etiologies. Results From 237 studies identified, 17 studies encompassing 1692 infants were selected. Idiopathic neonatal hepatitis (INH) occurred in 26.0 % of cases; the most common specific etiologies were extrahepatic biliary atresia (EHBA) (25.89 %), infection (11.47 %), TPN- associated cholestasis (6.44 %), metabolic disease (4.37 %), alpha-1 anti-trypsin deficiency (4.14 %), and perinatal hypoxia/ischemia (3.66 %). CMV was the most common infection identified (31.51 %) and galactosemia (36.49 %) was the most common metabolic disease identified. Limitations Major limitations are: (1) inconsistencies in the diagnostic evaluations among the different studies and (2) variations among the sample populations. Conclusions INH is the most common diagnosis for conjugated hyperbilirubinemia in infancy while EHBA and infection are the most commonly identified etiologies. The present review is intended to be a guide to the differential diagnosis and evaluation of the infant presenting with conjugated hyperbilirubinemia.
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Affiliation(s)
| | - Michael T Del Vecchio
- Department of Pediatrics, Temple University School of Medicine, 3440 N. Broad St., Philadelphia, PA, 19104, USA
| | - Stephen C Aronoff
- Department of Pediatrics, Temple University School of Medicine, 3440 N. Broad St., Philadelphia, PA, 19104, USA.
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Dani C, Pratesi S, Raimondi F, Romagnoli C. Italian guidelines for the management and treatment of neonatal cholestasis. Ital J Pediatr 2015; 41:69. [PMID: 26428285 PMCID: PMC4591626 DOI: 10.1186/s13052-015-0178-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Accepted: 09/22/2015] [Indexed: 02/08/2023] Open
Abstract
Hyperbilirubinemia is a frequent condition affecting newborns during the first two weeks of life and when it lasts more than 14 days it is defined as prolonged jaundice. This condition requires differential diagnosis between the usually benign unconjugated hyperbilirubinemia and the pathological conjugated hyperbilirubinemia, that is mainly due to neonatal cholestasis. It is important that the diagnosis of neonatal cholestasis be well-timed to optimize its management, prevent worsening of the patient’s outcome, and to avoid premature, painful, expensive, and useless tests. Unfortunately, this does not always occur and, therefore, the Task Force on Hyperbilirubinemia of the Italian Society of Neonatology presents these shared Italian guidelines for the management and treatment of neonatal cholestasis whose overall aim is to provide a useful tool for its assessment for neonatologists and family pediatricians.
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Affiliation(s)
- Carlo Dani
- Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Largo Brambilla 3, Florence, 50141, Italy.
| | - Simone Pratesi
- Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
| | - Francesco Raimondi
- Division of Neonatology, Section of Pediatrics Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
| | - Costantino Romagnoli
- Division of Neonatology, Department of Pediatrics, Catholic University of Sacred Heart, Rome, Italy.
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Almadhoun O, Rivera-Penera T, Lipeski L. Neonatal Graves’ Disease and Cholestatic Jaundice: Case Series and Review of the Literature. ACTA ACUST UNITED AC 2015. [DOI: 10.4236/ojped.2015.52027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Fattah S, Augustijns P, Annaert P. Age-dependent activity of the uptake transporters Ntcp and Oatp1b2 in male rat hepatocytes: from birth till adulthood. Drug Metab Dispos 2015; 43:1-8. [PMID: 25305012 DOI: 10.1124/dmd.114.059212] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Recognition of the role of hepatic drug transporters in elimination of xenobiotics continues to grow. Hepatic uptake transporters, such as hepatic isoforms of the organic anion-transporting polypeptide (Oatp) family as well as the bile acid transporter Na(+)-taurocholate cotransporting polypeptide (Ntcp) have been studied extensively both at the mRNA and protein expression levels in adults. However, in pediatric/juvenile populations, there continues to be a knowledge gap about the functional activity of these transporters. Therefore, the aim of this study was to examine the functional maturation of Ntcp and Oatp isoforms as major hepatic transporters. Hepatocytes were freshly isolated from rats aged between birth and 8 weeks. Transporter activities were assessed by measuring the initial uptake rates of known substrates: taurocholate (TCA) for Ntcp and sodium fluorescein (NaFluo) for Oatp. Relative to adult values, uptake clearance of TCA in hepatocytes from rats aged 0, 1, 2, 3, and 4 weeks reached 19, 43, 22, 46, and 63%, respectively. In contrast, Oatp-mediated NaFluo uptake showed a considerably slower developmental pattern: uptake clearance of NaFluo in hepatocytes from rats aged 0, 1, 2, 3, 4, and 6 weeks were 24, 20, 19, 8, 19, and 64%, respectively. Maturation of NaFluo uptake activity correlated with the previously reported ontogeny of Oatp1b2 mRNA expression, confirming the role of Oatp1b2 for NaFluo uptake in rat liver. The outcome of this project will help in understanding and predicting age-dependent drug exposure in juvenile animals and will eventually support safe and more effective drug therapies for children.
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Affiliation(s)
- Sarinj Fattah
- Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
| | - Patrick Augustijns
- Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
| | - Pieter Annaert
- Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
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Thibault M, McMahon J, Faubert G, Charbonneau J, Malo J, Ferreira E, Mohamed I. Parenteral nutrition-associated liver disease: a retrospective study of ursodeoxycholic Acid use in neonates. J Pediatr Pharmacol Ther 2014; 19:42-8. [PMID: 24782691 DOI: 10.5863/1551-6776-19.1.42] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To verify the effect of ursodeoxycholic acid (UDCA) on the duration of neonatal parenteral nutrition-associated liver disease. METHODS Retrospective cohort study of neonates in intensive care between 2004 and 2007 presenting with parenteral nutrition-associated liver disease. RESULTS Of 118 eligible infants, 64 received UDCA. Cholestasis lasted longer in the UDCA group (79 vs. 50 days, p=0.001). However, treatment was delayed for a median of 24 days after cholestasis onset. Multivariate Cox regression analysis showed no association between UDCA and cholestasis duration. The rate of decline of conjugated bilirubin was greater in treated patients (median 0.084 mg/dL/day vs. 0.60 mg/dL/day; p=0.009) and weight gain was greater (22.8 vs. 17.7 g/kg/day, p=0.010). CONCLUSIONS UDCA therapy was not associated with the duration of parenteral nutrition-associated liver disease. A delay in treatment initiation might explain this result. UDCA therapy was associated with a faster decline of conjugated bilirubin and greater weight gain.
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Affiliation(s)
- Maxime Thibault
- Department of Pharmacy, CHU Sainte-Justine, Montreal, Canada
| | - Jessica McMahon
- Department of Pharmacy, CHU Sainte-Justine, Montreal, Canada
| | | | | | - Josianne Malo
- Department of Pharmacy, CHU Sainte-Justine, Montreal, Canada
| | - Ema Ferreira
- Department of Pharmacy, CHU Sainte-Justine, Montreal, Canada ; Faculty of Pharmacy, University of Montreal, Montreal, Canada
| | - Ibrahim Mohamed
- Faculty of Medicine, University of Montreal, Montreal, Canada
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Management of neonatal cholestasis: Consensus statement of the pediatric gastroenterology chapter of Indian academy of pediatrics. Indian Pediatr 2014; 51:203-10. [DOI: 10.1007/s13312-014-0375-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Talachian E, Bidari A, Mehrazma M, Nick-khah N. Biopsy-driven diagnosis in infants with cholestatic jaundice in Iran. World J Gastroenterol 2014; 20:1048-1053. [PMID: 24574777 PMCID: PMC3921528 DOI: 10.3748/wjg.v20.i4.1048] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Revised: 11/06/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the frequencies of diagnoses confirmed by liver biopsy in infants with cholestasis in an Iranian pediatric hospital.
METHODS: This was a retrospective study conducted in a tertiary referral children’s hospital in Iran. We retrieved all pathology reports of liver biopsies from children less than two years of age who had presented for evaluation of cholestatic jaundice from March 2001 to March 2011. Additional specimen samples obtained from archived pathology blocks were reviewed by a pathologist blinded to the final diagnosis. These results were compared with the pathology reports from chart records to ensure consensus and eliminate any inconsistencies in final diagnoses. A structured checklist was used to gather information on multiple variables including age, sex, gestational age at birth, birth weight, age at which hyperbilirubinemia manifested, presence and identification of associated anomalies, clinical manifestations, and histological findings from liver biopsies. The baseline data are reported using descriptive statistics, and differences between groups were assessed by Fisher’s exact test and Student’s t test when indicated.
RESULTS: Fifty-five cases (28 females; 27 males) of infantile cholestasis (IC) were included in this study. The mean serum total bilirubin and direct bilirubin at presentation were 13.6 ± 5.9 and 7.3 ± 3.4, respectively. Forty cases (72.7%) were the product of term pregnancies. Common associated clinical findings were acholic stool in 33 cases (60.0%), hepatomegaly in 30 cases (54.5%), and dark-colored urine in 21 cases (38.2%). Biliary atresia (BA) was the most frequent diagnosis, found in 32 cases (58.2%), followed by intrahepatic bile duct paucity found in 6 cases (10.9%), metabolic disease in 6 cases (10.9%), idiopathic neonatal hepatitis in 5 cases (9.1%), choledochal cyst in 2 cases (3.6%), liver cirrhosis in 2 cases (3.6%), and progressive familial intrahepatic cholestasis and portal fibrosis each in 1 case (1.8%). The mean times for jaundice onset and liver biopsy were 43.8 and 102.0 d, respectively. In BA, the mean age at jaundice presentation was 21 d and for liver biopsy was 87.5 d, representing a mean delay of 66.5 d.
CONCLUSION: A significant delay was found between IC presentation and liver biopsy, which is detrimental in conditions that can cause irreversible liver damage, such as BA.
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Abstract
BACKGROUND AND OBJECTIVES Cholestasis affects 50% of extremely low-birth-weight infants. Its etiology remains poorly understood and the extent of liver injury in these infants is unclear. The premature baboon model provides an opportunity to study neonatal liver disease. We characterize hepatic histopathologic changes in this model. METHODS Archival tissue and data were obtained from the Southwest Foundation for Biomedical Research Primate Center, San Antonio, TX. Animals were selected based on history of antenatal steroid therapy and absence of sepsis or necrotizing enterocolitis with a protocol duration of at least 21 days and no early death (n = 45). Baboons had been treated per protocol in the neonatal intensive care unit (NICU). At necropsy, liver tissue was harvested and stored. Tissues from fetal gestational controls at similar ages were used for comparison (n = 28). Histologic changes were scored by consensus of 2 pathologists blinded to treatment group. Descriptive and comparative statistics were performed. RESULTS Control fetal livers had extramedullary hematopoiesis (EMH) that decreased across the gestational range. There was evidence of hepatocyte iron storage and ongoing portal tract development. Livers of NICU-treated baboons had increased Kupffer cell hypertrophy and hemosiderosis. There was a shift away from erythroid EMH toward increased myeloid EMH. There was increased cholestasis, ductular proliferation, portal tract fibrosis, and steatosis in treated animals. CONCLUSIONS We found pathologic changes in NICU-treated baboons comparable with findings reported in human infants. The baboon model of prematurity may be a useful tool to explore cholestasis and liver dysfunction in extremely low-birth-weight infants.
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Siu LY, Wong KN, Li KW, Kwong NS. Outcome of hepatobiliary scanning: preterm versus full-term cholestatic infants. J Paediatr Child Health 2013; 49:E46-51. [PMID: 23279199 DOI: 10.1111/jpc.12067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/06/2012] [Indexed: 11/30/2022]
Abstract
OBJECTIVES The aims of this study were to evaluate the specificity of a non-draining hepatobiliary scintigraphy (HBS) for biliary atresia (BA) in preterm and full-term babies, to verify the relationship between non-draining scan and higher levels of direct bilirubin and to find an objective criterion to guide the time in performing HBS. METHODS A total of 175 infants (113 males and 62 females, median age of 45 days) with 181 HBS performed in Tuen Mun Hospital between January 1998 and May 2010 were retrospectively analysed. A 'non-draining' scan was defined as one showing no excretion of radiolabelled tracer into the small bowel 24 h after injection. The disease category, epidemiological and laboratory data were compared between infants having non-draining and draining scans. In addition, the predictive value of a negative scan for BA was compared between preterm and full-term infants. RESULTS Twenty infants (11.4%) were surgically confirmed to have BA. A non-draining scan was found to be 100% sensitive for BA, and the specificity was 96% and 78% among full-term infants and preterm infants, respectively. The mean direct bilirubin values of infants with BA and intrahepatic cholestasis were 141.9 and 111.3 μmol/L, respectively, which were significantly higher than 67.2 μmol/L seen in infants with draining scans. This analysis shows that using direct bilirubin ≥63 μmol/L as an objective criterion in guiding the time to perform HBS is most cost-effective. CONCLUSION Our data supported that using direct bilirubin ≥63 μmol/L as an objective criterion in guiding the time to perform HBS will avoid unnecessary scans.
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Affiliation(s)
- Luen Yee Siu
- Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, New Territories, Hong Kong, China.
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Blackmer AB, Bailey E. Management of Copper Deficiency in Cholestatic Infants. Nutr Clin Pract 2012; 28:75-86. [DOI: 10.1177/0884533612461531] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Allison Beck Blackmer
- Department of Pharmacy Services/College of Pharmacy, University of Michigan, Ann Arbor
| | - Elizabeth Bailey
- Patient Food and Nutrition Services, University of Michigan, Ann Arbor
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Taba R, Yamakawa M, Miyakoshi C, Imai Y. Refractory cholestasis presenting as cholangiolitis in an Rh (E)-incompatible neonate. J Paediatr Child Health 2012; 48:E126-31. [PMID: 21040076 DOI: 10.1111/j.1440-1754.2010.01874.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Cholestasis in neonates is infrequently associated with Rh isoimmunization, and usually resolves within a month. The suggested pathophysiology is inspissated bile and hepatocellular damage. We report a rare case of refractory cholestasis presenting with cholangiolitis in a newborn with anti-E isoimmunisation. The cholangiolitis was disclosed by immunohistochemical investigation of conjugated hyperbilirubinaemia and by liver biopsy, which showed a number of CD8(+) lymphocytes within the portal tract damaging the interlobular bile duct. Bilirubin levels dramatically decreased after 14-day corticosteroid therapy (prednisolone, 2 mg/kg/day) implying that the cause of cholestasis could be immune-mediated cholangiolitis.
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Affiliation(s)
- Ryusuke Taba
- Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe, Japan.
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Role of Abdominal Sonography in the Preoperative Diagnosis of Extrahepatic Biliary Atresia in Infants Younger Than 90 Days. AJR Am J Roentgenol 2011; 196:W438-45. [DOI: 10.2214/ajr.10.5180] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Tufano M, Nicastro E, Giliberti P, Vegnente A, Raimondi F, Iorio R. Cholestasis in neonatal intensive care unit: incidence, aetiology and management. Acta Paediatr 2009; 98:1756-1761. [PMID: 19664101 DOI: 10.1111/j.1651-2227.2009.01464.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
AIM Prevalence, aetiology, management and outcome of cholestasis were evaluated in infants admitted to neonatal intensive care unit (NICU). METHODS Medical records of all infants admitted to two Italian level III NICUs from January 2005 to August 2007 were retrospectively reviewed. The role of ursodeoxycholic acid (UDCA) therapy was also investigated. RESULTS Twenty-seven of 1289 enrolled infants developed cholestasis. In 25 infants, cholestasis had a multifactorial basis, while in two, no aetiology was found. UDCA did not significantly affect clinical and biochemical course of cholestasis. During a period of 12 months, eight cholestatic infants died, one underwent liver transplantation and 18 fully recovered. CONCLUSION Infants admitted in NICU have a rate of cholestasis higher than that reported in the general population of live births; in most cases, cholestasis is associated to multiple risk factors and shows a favourable outcome. UDCA does not seem to affect clinical course of cholestasis in this setting.
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MESH Headings
- Bilirubin/blood
- Cholestasis/drug therapy
- Cholestasis/epidemiology
- Cholestasis/etiology
- Female
- Humans
- Incidence
- Infant, Newborn
- Infant, Premature
- Infant, Premature, Diseases/drug therapy
- Infant, Premature, Diseases/epidemiology
- Infant, Premature, Diseases/etiology
- Intensive Care Units, Neonatal
- Intensive Care, Neonatal/methods
- Italy/epidemiology
- Logistic Models
- Male
- Retrospective Studies
- Statistics, Nonparametric
- Treatment Outcome
- Ursodeoxycholic Acid/therapeutic use
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Affiliation(s)
- Maria Tufano
- Department of Pediatrics, University of Naples Federico II, Naples, Italy
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Lee H, Kang J, Kim KM, Jang JY, Jang SJ, Yu E. The Clinicopathological Parameters for Making the Differential Diagnosis of Neonatal Cholestasis. KOREAN JOURNAL OF PATHOLOGY 2009. [DOI: 10.4132/koreanjpathol.2009.43.1.43] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Heejin Lee
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jun Kang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Joo Young Jang
- Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Se-jin Jang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Eunsil Yu
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Abstract
This study aimed to provide the analysis of clinical presentation, results of laboratory and imaging investigations as well as clinical outcome of children with cholestasis. Infants with neonatal cholestasis referred to Children's Hospital from 2002 to 2007 were participated in the study in a cross-sectional prospective study. Appropriate diagnostic criteria and tests were employed for diagnosis the underlying etiologies of neonatal cholestasis. One year mortality rate was determined. One hundred twenty one infants, 75 males and 46 females, with the mean age of 58.3 +/- 15.3 (14-120) days were enrolled in study. Jaundice (94.2%) and hepatomegaly (66.1%) were the most frequent symptom and signs on admission. Idiopathic neonatal hepatitis (36.4%), extrahepatic biliary atresia (24.8%), metabolic disease (20.7%), intrahepatic ductal paucity (10.7%), intrauterine infection (3.3%) were the most frequent causes of neonatal cholestasis. One year mortality was 5.8%. There is still not one effective and specific diagnostic method in differentiating between the causes of cholestasis in the newborns and infants. Some potentially important differences in the disease pattern, initial presentation and long-term outcome are suggested from the present study when compared to previous reports from other parts of the world.
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Affiliation(s)
- Mandana Rafeey
- Department of Pediatric Gastroenterology, Liver and Gastroenterology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Steinbach M, Clark RH, Kelleher AS, Flores C, White R, Chace DH, Spitzer AR. Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant. J Perinatol 2008; 28:129-135. [PMID: 18059467 DOI: 10.1038/sj.jp.7211889] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2007] [Revised: 10/17/2007] [Accepted: 10/23/2007] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice. STUDY DESIGN We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. RESULT We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.
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Affiliation(s)
- M Steinbach
- Pediatrix-Obstetrix Center for Research and Education and Pediatrix Analytical, Sunrise, FL, USA
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Abstract
JAUNDICE IS OFTEN SEEN IN the neonatal period, with 60 percent of full-term and 80 percent of preterm infants having visible jaundice.1 Jaundice is a sign of hyperbilirubinemia, which, in the newborn period, is usually due to an elevated indirect or unconjugated bilirubin level, and may result from an exaggerated physiologic response or be pathologic in nature. Hyperibilirubinemia due to an elevated direct or conjugated bilirubin is less common. Although an elevated direct bilirubin level can be transient, it is often related to some pathology.
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Affiliation(s)
- Jodi M Beachy
- Doctors Hospital, Columbus Childrens Hospital Neonatal Special Care Unit, Ohio, USA
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Nwomeh BC, Caniano DA, Hogan M. Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography. Pediatr Surg Int 2007; 23:845-9. [PMID: 17605021 DOI: 10.1007/s00383-007-1938-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/08/2007] [Indexed: 10/23/2022]
Abstract
Definitive exclusion of biliary atresia in the infant with cholestatic jaundice usually requires operative cholangiography. This approach suffers from the disadvantage that sick infants are subjected to a time-consuming and potentially negative surgical exploration. The purpose of this study was to determine if percutaneous cholecystocholangiography (PCC) prevents unnecessary laparotomy in infants whose cholestasis is caused by diseases other than biliary atresia. This study is a 10 year retrospective review of all infants with persistent direct hyperbilirubinemia and inconclusive biliary nuclear scans who underwent further evaluation for suspected biliary atresia. A gallbladder ultrasound (US) was obtained in all patients. When the gallbladder was visualized, further imaging by PCC was done under intravenous sedation; otherwise, the standard operative cholangiogram (OCG) was performed, with liver biopsy as indicated. The primary outcome was the diagnostic accuracy of PCC, especially with respect to preventing a laparotomy. There were 35 infants with suspected biliary atresia, with a mean age of 8 weeks (range 1-14 weeks). Nine infants whose gallbladder was visualized by ultrasound underwent PCC that definitively excluded biliary atresia. Of this group, the most frequent diagnosis (five patients) was total parenteral nutrition-associated cholestasis. The other 26 infants with absent or decompressed gallbladder had laparotomy and OCG, which identified biliary atresia in 16 patients (61%). Laparotomy was avoided in all 9 patients who underwent PCC, thus reducing the negative laparotomy rate by 47%. There were no complications associated with PCC. Several alternative techniques to operative cholangiogram have been described for the definitive exclusion of biliary atresia, but many of these have distinct drawbacks. Advances in interventional radiology techniques have permitted safe percutaneous contrast evaluation of the biliary tree. Identification of a normal gall bladder on sonogram is highly predictive of the absence of biliary atresia. Further confirmation can be accurately obtained by a combination of PCC and percutaneous liver biopsy.
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Affiliation(s)
- Benedict C Nwomeh
- Division of Pediatric Surgery, Columbus Children's Hospital, The Ohio State University College of Medicine & Public Health, 700 Children's Drive, Suite ED379, Columbus, OH 43205, USA.
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Barrington KJ, Sankaran K. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants. Paediatr Child Health 2007. [DOI: 10.1093/pch/12.suppl_b.1b] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Okçu-Heper A, Erden E, Doganci T, Kuloglu Z, Kansu A, Genc Y. Nonobstructive neonatal cholestasis: clinical outcome and scoring of the histopathological changes in liver biopsies. Pediatr Dev Pathol 2006; 9:44-51. [PMID: 16808634 DOI: 10.2350/06-05-0073.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2005] [Accepted: 08/26/2005] [Indexed: 11/20/2022]
Abstract
The clinical outcome of nonobstructive neonatal cholestasis (NC) cases varies greatly and the prognosis is generally unpredictable. In this study, we aimed to evaluate the prognostic benefits of qualitative analysis of histopathological changes in nonobstructive NC cases. A total of 28 nonobstructive NC cases (18 neonatal hepatitis; 10 intrahepatic bile duct paucity) were studied. We analyzed the relationship between histopathological and clinical parameters. Hepatic inflammation, bridging necrosis, pericellular fibrosis, giant cell transformation, and extramedullary hematopoiesis were evaluated and scored according to their absence or presence in each case. The sum of the histopathological scores was accepted as "total pathological injury score." The height percentiles, the presence and the degree of hepatomegaly and ascites, and serum alanine aminotransferase (ALT), albumin, and bilirubin levels and prothrombin time were also evaluated and scored. The patients were divided into 2 clinical course groups considered "good" or "bad" according to the total clinical scores. For statistical analysis, Pearson's chi-square test, Mann-Whitney U-test, and receiver operating characteristic curve were used. We found a statistically significant negative relation between the clinical course and total pathological injury score (P = 0.042) and pericellular fibrosis (P = 0.016). In conclusion, during the interpretation of liver biopsies of nonobstructive NC, scoring of histopathological changes should be done for assessing the clinical prognostic outcome.
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Affiliation(s)
- Aylin Okçu-Heper
- Department of Pathology, Ankara University, School of Medicine, Patoloji Anabilim Dali, Morfoloji Binasi, 06100, Sihhiye, Ankara, Turkey.
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