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Clinical Chemistry Feb 2018
Topics: Alagille Syndrome; Female; Hashimoto Disease; Humans; Hyperthyroidism; Hyponatremia; Infant
PubMed: 29378746
DOI: 10.1373/clinchem.2017.276501 -
Postepy W Kardiologii Interwencyjnej =... Jun 2022Alagille syndrome, caused by mutations in the gene encoding (), a ligand in the Notch signaling pathway, is an autosomal dominant disorder with developmental... (Review)
Review
Alagille syndrome, caused by mutations in the gene encoding (), a ligand in the Notch signaling pathway, is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, face and skeleton. The aim of the present study is try to disclose the clinical features, management and outcomes of pulmonary artery stenosis associated with Alagille syndrome. By comprehensive literature retrieval, 38 articles involving 401 patients were recruited for this study. The pertinent variables closely related to pulmonary artery stenosis in patients with Alagille syndrome were comprehensively analyzed by following the PRISMA guidelines. The management of pulmonary artery pathologies, especially a severe type of pulmonary artery stenosis in Alagille syndrome, is a concerned matter. Publications of literature retrieval of recent 3 decades were the study material of this article. The pulmonary artery pathologies, especially the severe type of pulmonary artery stenosis in Alagille syndrome, warrant surgical or interventional treatments. After the procedures, the right ventricular to left ventricular pressure ratio was reduced by 25%. There were no intergroup differences in terms of recovery, reintervention and mortality rates between interventionally and surgically treated patients. Transcatheter treatment is preferable due to less trauma. Surgical treatment of pulmonary artery stenosis can be performed currently with intracardiac defect repair.
PubMed: 36051836
DOI: 10.5114/aic.2022.118526 -
American Journal of Physiology.... Jul 2017During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and... (Review)
Review
During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including fetal demise. The course of preexisting cholestatic conditions in pregnancy is considered, including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, and Alagille syndrome. The currently accepted treatments for cholestasis in pregnancy and promising new therapeutics for the condition are described.
Topics: Cholestasis, Intrahepatic; Female; Humans; Pregnancy; Pregnancy Complications
PubMed: 28450276
DOI: 10.1152/ajpgi.00028.2017 -
Surgical Pathology Clinics Jun 2018The inherited diseases causing conjugated hyperbilirubinemia are diverse, with variability in clinical severity, histologic appearance, and time of onset. The liver... (Review)
Review
The inherited diseases causing conjugated hyperbilirubinemia are diverse, with variability in clinical severity, histologic appearance, and time of onset. The liver biopsy appearances can also vary depending on whether the initial presentation is in the neonatal period or later. Although many of the disorders have specific histologic features in fully developed and classic cases, biopsies taken early in the disease course may be nonspecific, showing either cholestatic hepatitis or an obstructive pattern of injury requiring close correlation with the laboratory and clinical findings to reach the correct diagnosis. Additionally, increased understanding of the range of hepatic changes occurring in mild deficiencies of bile canalicular transporter proteins suggest that these disorders, particularly ABCB4 deficiency, may be more common than previously recognized; improved awareness should prompt further investigation.
Topics: ATP Binding Cassette Transporter, Subfamily B; Alagille Syndrome; Biopsy; Cholestasis; Cholestasis, Intrahepatic; Cystic Fibrosis; Genetic Diseases, Inborn; Humans; Liver; alpha 1-Antitrypsin Deficiency
PubMed: 29751877
DOI: 10.1016/j.path.2018.02.001 -
Therapeutic Advances in Gastroenterology 2023Pruritus is a symptom of several cholestatic liver diseases (CLDs) that can impair health-related quality of life (HRQoL). Despite evidence-based guideline therapy,... (Review)
Review
BACKGROUND
Pruritus is a symptom of several cholestatic liver diseases (CLDs) that can impair health-related quality of life (HRQoL). Despite evidence-based guideline therapy, managing cholestatic pruritus (CP) remains challenging, thus making the need for newer, more effective therapeutic agents more evident.
OBJECTIVE
Our study evaluated the efficacy of existing CP therapies.
DESIGN
Systematic review.
DATA SOURCES
From inception until March 2023, we conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus, ClinicalTrial.gov, and other sources, including pharmaceutical webpages and conference proceedings published in English that reported on CP interventions.
METHODS
Two reviewers independently conducted screening and full-text review of articles with extraction conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The methodological quality of studies included in our qualitative synthesis was assessed by using the Cochrane ROBINS-I and ROBINS-II tools for interventional studies and the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The primary outcome assessed in our systematic review was the severity of CP after therapy.
RESULTS
Of 3293 screened articles, 92 studies were eligible for inclusion in the qualitative synthesis. Some patients' HRQoL improved with evidence-based standard therapy. Others, particularly those with severe and refractory CP, often required conversion to or addition of experimental noninvasive (e.g., ondansetron) or extracorporeal liver support to alleviate CP. In addition, studies investigating a newer class drug, the ileal bile acid transporter inhibitor (IBATi), demonstrate its effectiveness in reducing serum bile acid and alleviating CP with sustained improvement noted in patients with the inherited childhood cholestatic disorders - progressive familial intrahepatic cholestasis and Alagille syndrome.
CONCLUSION
Our findings consolidate data on the efficacy of guideline-based approaches and newer therapies for CP. While the initial findings are promising, additional clinical trials will be needed to determine the full extent of IBATi's efficacy and potential use in treating other common CLDs. These results provide a foundation for future research and highlight the need for continued investigation into the management and treatment of CLDs.
PubMed: 37255856
DOI: 10.1177/17562848231172829 -
Current Opinion in Pediatrics Oct 2022Cholestasis in infants can indicate a serious hepatobiliary disease and requires timely assessment, diagnosis and intervention to prevent progression to serious liver... (Review)
Review
PURPOSE OF REVIEW
Cholestasis in infants can indicate a serious hepatobiliary disease and requires timely assessment, diagnosis and intervention to prevent progression to serious liver decompensation. This report aims to highlight recently published studies regarding diagnosis and treatment of cholestasis in infants.
RECENT FINDINGS
The evaluation of neonatal cholestasis can be challenging, requiring the assessment of a broad differential diagnosis in timely fashion. The Italian Society of pediatric gastroenterology, hepatology, and nutrition position paper on the evaluation of neonatal cholestasis is reviewed and compared to other published guidelines. In biliary atresia, the most time-sensitive of these diagnoses, serum matrix metalloproteinase-7 was studied in Japanese infants with biliary atresia with excellent diagnostic performance characteristics. Genetic testing panels are an increasingly used tool to help identify causes of cholestasis. An American experience of genetic testing in large cohort of infants identified a definite or possible genetic diagnosis in 11% of cholestatic infants. In the treatment of prutitus in Alagille syndrome and progressive familial intrahepatic cholestasis the clinical studies of two newly Food and Drug Administration approved ileal bile acid transport inhibitors are discussed. New information on the prevalence of cytomegalovirus and idiopathic cholestasis as other etiologies of infant cholestasis is also reviewed. Lastly, new insight on potential maternal microbiome regulation on biliary disease in neonates on experimental biliary atresia models is discussed.
SUMMARY
Cholestasis in infants requires timely diagnosis and intervention. There are exciting new diagnostic and treatment options now being studied which could help minimize the likelihood of advanced liver disease and development of serious complications.
Topics: Biliary Atresia; Child; Cholestasis; Cholestasis, Intrahepatic; Diagnosis, Differential; Humans; Infant; Infant, Newborn
PubMed: 35942658
DOI: 10.1097/MOP.0000000000001156 -
Pediatric Surgery International Oct 2018Infants with Alagille syndrome (AGS) frequently develop neonatal cholestasis, and some AGS infants who suspected of biliary atresia subsequently undergo the Kasai... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Infants with Alagille syndrome (AGS) frequently develop neonatal cholestasis, and some AGS infants who suspected of biliary atresia subsequently undergo the Kasai operation with the diagnosis of biliary atresia. The aim of this study was to investigate the effect of the Kasai operation on liver and patient outcomes among AGS patients, using a meta-analysis.
METHODS
A systematic review and meta-analysis of studies describing the outcomes of AGS patients with/without the Kasai operation were conducted. The analyzed outcomes were liver transplantation, not living with the native liver, and mortality for any reason.
RESULTS
We identified 6 studies (394 AGS patients). All studies were retrospective cohort or case-control studies. The incidences of liver transplantation, not living with the native liver, and mortality were significantly higher in AGS patients who underwent the Kasai operation than in those who did not undergo the Kasai operation (odds ratio: 6.46, 95% CI 3.23-12.89, p < 0.00001; odds ratio: 25.88, 95% CI 2.83-236.84, p < 0.004; odds ratio: 15.05, 95% CI 2.70-83.93, p = 0.002, respectively).
CONCLUSION
The Kasai operation was associated with poor outcomes in AGS patients. It remains unclear if the Kasai operation directly deteriorates liver and patient outcomes in AGS patients.
Topics: Alagille Syndrome; Female; Humans; Infant; Male; Portoenterostomy, Hepatic; Retrospective Studies; Treatment Outcome
PubMed: 30073479
DOI: 10.1007/s00383-018-4316-3 -
Pediatric Gastroenterology, Hepatology... Mar 2016Cholestasis results from impairment in the excretion of bile, which may be due to mechanical obstruction of bile flow or impairment of excretion of bile components into... (Review)
Review
Cholestasis results from impairment in the excretion of bile, which may be due to mechanical obstruction of bile flow or impairment of excretion of bile components into the bile canaliculus. When present, cholestasis warrants prompt diagnosis and treatment. The differential diagnosis of cholestasis beyond the neonatal period is broad and includes congenital and acquired etiologies. It is imperative that the clinician differentiates between intrahepatic and extrahepatic origin of cholestasis. Treatment may be supportive or curative and depends on the etiology. Recent literature shows that optimal nutritional and medical support also plays an integral role in the management of pediatric patients with chronic cholestasis. This review will provide a broad overview of the pathophysiology, diagnostic approach, and management of cholestasis beyond the neonatal and infancy periods.
PubMed: 27066444
DOI: 10.5223/pghn.2016.19.1.1 -
EMBO Molecular Medicine Dec 2022Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in...
Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1 mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1 mice, using retina as a model. Jag1 mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1 mice represent a new model for vascular compromise in ALGS.
Topics: Female; Male; Animals; Mice; Alagille Syndrome; Sex Characteristics; Retina; Risk Factors
PubMed: 36345711
DOI: 10.15252/emmm.202215809 -
Gene Jan 2016Jagged1 (JAG1) is one of the 5 cell surface ligands that functions primarily in the highly conserved Notch signaling pathway. Notch signaling plays a critical role in... (Review)
Review
Jagged1 (JAG1) is one of the 5 cell surface ligands that functions primarily in the highly conserved Notch signaling pathway. Notch signaling plays a critical role in cellular fate determination and is active throughout development and across many organ systems. The classic JAG1-NOTCH interaction leads to a cascade of proteolytic cleavages resulting in the NOTCH intracellular domain being transported into the nucleus where it functions to activate downstream transcription of target genes. JAG1 mutations have been associated with several disorders including the multi-system dominant disorder Alagille syndrome, and some cases of tetralogy of Fallot (although these may represent variable expressivity of Alagille syndrome). In addition, variations in JAG1 have been found to be associated with multiple types of cancer including breast cancer and adrenocortical carcinoma. Alagille syndrome, which primarily affects the liver, heart, skeleton, eye, face, kidney and vasculature is caused by loss of function mutations in JAG1, demonstrating that haploinsufficiency for JAG1 is disease causing, at least in these tissues. Expression and conditional gene knockout studies of JAG1 (Jag1) have correlated with tissue-specific disease phenotypes and have provided insight into both disease pathogenesis and human development.
Topics: Alagille Syndrome; Calcium-Binding Proteins; Gene Knockdown Techniques; Genetic Predisposition to Disease; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Membrane Proteins; Neoplasms; Pulmonary Valve Stenosis; Serrate-Jagged Proteins; Tetralogy of Fallot
PubMed: 26548814
DOI: 10.1016/j.gene.2015.10.065