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Hepatocellular vacuolar degeneration and canalicular cholestasis (HEx400)
Source publication
Neonatal cholestasis is a rare presenting feature of cystic fibrosis which usually cannot be differentiated from other types of cholestasis. Herein, the authors report a 63 d-old boy with cystic fibrosis presenting with neonatal cholestasis mimicking biliary atresia. A new mutation in CFTR gene resulting in severe phenotype has been described. The...
Context in source publication
Context 1
... scintig- raphy revealed a normal hepatic uptake of the tracer, reten- tion of the radioactivity in the liver and lack of excretion to the small intestine up to 24 h post-infusion. Percutaneous liver biopsy showed canalicular cholestasis and extensive vacuolar degeneration in hepatocytes without appreciable inflammation and bile duct proliferation (Fig. 1). DNA sequence analysis of the exons and exon-intron boundaries of the CFTR gene revealed a homozygous nonsense muta- tion, c.3871 G>T (p.G1247X), in exon 23 (Fig. 2). The mutation is predicted to cause a premature stop in CFTR transcription and therefore be deleterious (Fig. 3). With sup- portive treatments including ursodeoxycholic ...
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Purpose
Kasai portoenterostomy (KPE) is the only treatment currently available for biliary atresia (BA). Age at KPE and surgical experience are prognostic factors for a successful KPE. Here, we aimed to assess whether the size of bile ductules at the porta hepatis during KPE correlates with KPE success and transplant-free survival (TFS).
Methods
A...
Objectives
To explore the outcomes and related factors in children without cholangitis after Kasai portoenterostomy (KPE).
Methods
We retrospectively analyzed the data of infants with type III BA who underwent KPE from June 2016 to December 2021. We compared and analyzed the difference in native liver survival (NLS) rates in different types of cho...
Biliary atresia (BA) is the most prevalent serious liver disease of infancy and childhood, and the principal indication for liver transplantation in pediatrics. BA is best considered as an idiopathic panbiliary cholangiopathy characterized by obstruction of bile flow and consequent cholestasis presenting during fetal and perinatal periods. While a...
The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with activ...
Purpose.
Kasai portoenterostomy is the standard therapy for biliary atresia (BA). If Kasai is unsuccessful, there is controversy over whether revision of Kasai restores adequate biliary drainage. Although there are several reports of laparoscopic Kasai (Lap-Kasai), none has described laparoscopic revision (Lap-revision). The purposes of this study...
Citations
... Cystic fibrosis (CF) CF is an autosomal recessive disease that results from a mutation in the CF transmembrane regulator (CFTR) [88]. Recently, a novel mutation of CF, c. 3871 G > T, was identified [89]. Classic CF manifests with pulmonary symptoms, meconium ileus, recurrent pancreatitis or pancreatic insufficiency, and focal biliary cirrhosis due to the obstruction of the IHBDs [90]. ...
Background
Neonatal 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 text
NC 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.
Conclusion
Further 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.
... The prevalence of observed hepatomegaly (22.1%) is close to that reported in the literature (6-30%) [31]. However, the observed rate of neonatal cholestasis (11.7%) was different from the literature, where less than 2% of children with CF suffered from this condition [32]. An increase in liver enzymes (10.4%) within patients was observed. ...
Purpose
The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis.
Methods
A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations.
Results
Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0–297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02).
Conclusion
The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.
... [6] Recently, a novel mutation of CF, c. 3871 G > T, presenting with cholestasis that initially clinically resembled biliary atresia was described. [7] Our patient's mutation is R117H 5T; there have not been any reports of neonatal cholestasis associated with this mutation to our knowledge. ...
Cystic fibrosis (CF) has 20% associated rate of neonatal cholestasis. This presents in classic type CF, which initially can be confused with biliary atresia. Additionally, CF has been described with intestinal atresias but not duodenal atresia (DA). This is a case presentation highlighting a previously unreported presentation of R117H 5T CF mutation: A mutation that has recently been described and is not well-characterized. A retrospective review of single case was done. The newborn screen was sent per protocol. A 32 and 6/7 week gestation male was born with DA. Perinatal testing showed R117H mutation and 5T variant on separate chromosomes. His DA was repaired at 4 weeks of life. He had persistent jaundice, hepatobiliary iminodiacetic acid scan failed to identify the gallbladder, and raising concern for biliary atresia. At laparotomy, biliary tree was found to be normal on cholangiogram. Liver biopsy showed depleted interlobular bile ducts, with cholangiolar proliferation, consistent with CF induced cholestasis. This is an abnormal presentation for CF induced neonatal cholestasis and DA in the R117H 5T mutation that traditionally has been described as mild/atypical presentation of CF. Therefore, patients with this mutation who present with persistently elevated bilirubin should be evaluated for liver disease associated with CF.
... The resulting ductular biliary obstruction and portal inflammation may first cause a focal, but later multilobular fibrosis and cirrhosis. A recent case report refers to an infant with CF presenting with neonatal cholestasis mimicking biliary atresia, in whom a new CFTR mutation (c.3871 G>T) resulting in a severe phenotype has been described [53]. Among a range of candidate genes, SERPINA-1Z-allele has been identified as a modifier gene for the development of CFLD [45]. ...
Due to improved medical care, life expectancy in patients with cystic fibrosis (CF) has veritably improved over the last decades. Importantly, cystic fibrosis related liver disease (CFLD) has become one of the leading causes of morbidity and mortality in CF patients. However, CFLD might be largely underdiagnosed and diagnostic criteria need to be refined. The underlying pathomechanisms are largely unknown, and treatment strategies with proven efficacy are lacking. This review focuses on current invasive and non-invasive diagnostic standards, the current knowledge on the pathophysiology of CFLD, treatment strategies, and possible future developments.
Among the systemic impairment in cystic fibrosis there is also hepatobiliary tract involvement, with some genetic determinants of the disease manifesting as cystic fibrosis-associated liver disease (CFLD). The pathogenesis, natural history and cyrrhogenic evolution of CFLD are discussed in relation to the multiple phenotypes of cystic fibrosis. The CFLD therapy is nonspecific, the disease progression to cirrhosis is unpredictable, and the CFTR modulators offer a still underinvestigated therapeutic alternative.
It is uncommon for a patient to have 2 different diagnoses contributing to neonatal cholestasis and poor growth. We present a 2-month-old female with extrahepatic biliary atresia status after Kasai procedure at 4 weeks old presenting with persistent neonatal cholestasis. The patient was admitted for intolerance of oral feeds, concern for cholangitis and Kasai failure, and nutritional optimization. She was found to have genetic testing positive for 2 rare cystic fibrosis transmembrane conductance regulator mutations and pancreatic insufficiency consistent with a possible diagnosis of cystic fibrosis-related disease. We discuss the implications and management considerations in a patient with both biliary atresia and cystic fibrosis.
The diagnosis of biliary atresia is still terrifying at the 3rd decade of the 21st century. In a department of neonatal intensive care unit, parents and physicians face a challenge with a jaundiced baby, who may or may not have a surgically correctable hepatopathy. The approach has been systematically evaluated, but the etiology remains ambiguous. The study of families with recurrent biliary atresia has been undertaken at a molecular level. The primary interest with this disease is to identify the etiology and change the treatment from symptomatic to curative. The occurrence of this obstructive cholangio-hepatopathy in well-known genetic syndromes has suggested just coincidental finding, but the reality can be more intriguing because some of these diseases may have some interaction with the development of the intrahepatic biliary system. Several genes have been investigated thoroughly, including ADD3 and GPC1 shifting the interest from viruses to genetics. In this review, the intriguing complexities of this hepatobiliary disease are highlighted.
Highly effective modulator therapy (HEMT) for cystic fibrosis (CF) has been touted as one of the greatest advances to date in CF care. As these therapies are now available for many older children and adults with CF, marked improvement of their nutritional status, pulmonary and gastrointestinal symptoms have been observed. However, most infants and younger children are not current candidates for HEMT due to age and/or cystic fibrosis transmembrane conductance regulator (CFTR) mutation. For these young children, it is essential to provide rigorous monitoring and care to avoid potential disease sequelae while awaiting HEMT availability. The following article highlights recent advances in the care of infants and young children with CF with regard to surveillance and treatment of nutritional, pulmonary, and gastrointestinal disorders. Recent clinical trials in this population are also reviewed. This article is protected by copyright. All rights reserved.
Objective:
To explore the clinical characteristics and genetic findings of patients with infantile intrahepatic cholestasis.
Methods:
The clinical data were collected in children who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from June 2017 to June 2019 and were suspected of inherited metabolic diseases. Next generation sequencing based on target gene panel was used for gene analysis in these children. Sanger sequencing technology was used to verify the genes of the members in this family.
Results:
Forty patients were enrolled. Pathogenic gene variants were identified in 13 patients (32%), including SLC25A13 gene variation in 3 patients who were diagnosed with citrin deficiency, JAG1 gene variation in 3 patients who were diagnosed with Alagille syndrome, ABCB11 gene variation in 3 patients who were diagnosed with progressive familial intrahepatic cholestasis type 2, HSD3B7 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, AKR1D1 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, NPC1 gene variation in 1 patient who was diagnosed with Niemann-Pick disease, and CFTR gene variation in 1 patient who was diagnosed with cystic fibrosis.
Conclusions:
The etiology of infantile intrahepatic cholestasis is complex. Next generation sequencing is helpful in the diagnosis of infantile intrahepatic cholestasis.
