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![Relationship of aspartate aminotransferase (AST) levels with viral load in CMV +ve BA (n = 31), showing inverse correlation (rS = − 0.59; P = 0.002). [Reproduced with permission from [27]].](profile/Mark-Davenport/publication/369196058/figure/fig3/AS:11431281170902141@1687925878845/Relationship-of-aspartate-aminotransferase-AST-levels-with-viral-load-in-CMV-ve-BA-n.png)
Relationship of aspartate aminotransferase (AST) levels with viral load in CMV +ve BA (n = 31), showing inverse correlation (rS = − 0.59; P = 0.002). [Reproduced with permission from [27]].
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![Figure 3. Portal tract T cell subset quantification (Th-1 [A] and Th-17...](profile/Mark-Davenport/publication/369196058/figure/fig2/AS:11431281170892924@1687925878711/Portal-tract-T-cell-subset-quantification-Th-1-A-and-Th-17-B-according-to_Q320.jpg)
Introduction:
Biliary atresia is a potentially fatal condition of the bile ducts - both intra- and extrahepatic, for which we have no cure. Though principally a cholestatic condition, much of its pathology stems from its tendency to aggressively induce liver fibrosis and ultimately cirrhosis, only partially restrained by portoenterostomy.
Areas c...
Context in source publication
Context 1
... looked at plasma aspartate aminotransferase (AST) (as a surrogate marker of active 260 hepatocyte injury) at presentation in our cohort of IgM +ve BA infants (already higher than controls) and showed a negative correlation with CMV viral load. We interpreted this as that the liver damage was occurring in the viral clearance phase rather than the earlier stages of the viremia [27] (Figure 4). ...
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Background
Two-dimensional shear wave elastography (2D-SWE) has been proposed for detecting liver fibrosis in biliary atresia.
Objectives
To assess the performance of 2D-SWE for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia.
Materials and Methods
Five electronic databases were searched to identify studies invest...
Citations
... Despite being a complex and multifactorial disease, in 70-80% of cases no apparent defects found in other tissues or organs [16][17][18] . Theories abound with suggested causes ranging from toxins to viral infections to genetic susceptibility 15,[19][20][21] . What is clear is that obstruction of EHBD can cause subsequent liver injury in infants, leading to liver fibrosis and lifelong health problems 13,22,23 . ...
Background
Biliary atresia (BA) is an intractable disease of unknown cause that develops in the neonatal period. It causes jaundice and liver damage due to the destruction of extrahepatic biliary tracts,. We have found that heterozygous knockout mice of the SRY related HMG-box 17 (Sox17) gene, a master regulator of stem/progenitor cells in the gallbladder wall, exhibit a condition like BA. However, the precise contribution of hypoplastic gallbladder wall to the pathogenesis of hepatobiliary disease in Sox17 heterozygous embryos and human BA remains unclear.
Methods
We employed cholangiography and histological analyses in the mouse BA model. Furthermore, we conducted a retrospective analysis of human BA.
Results
We show that gallbladder wall hypoplasia causes abnormal multiple connections between the hilar hepatic bile ducts and the gallbladder-cystic duct in Sox17 heterozygous embryos. These multiple hilar extrahepatic ducts fuse with the developing intrahepatic duct walls and pull them out of the liver parenchyma, resulting in abnormal intrahepatic duct network and severe cholestasis. In human BA with gallbladder wall hypoplasia (i.e., abnormally reduced expression of SOX17), we also identify a strong association between reduced gallbladder width (a morphometric parameter indicating gallbladder wall hypoplasia) and severe liver injury at the time of the Kasai surgery, like the Sox17-mutant mouse model.
Conclusions
Together with the close correlation between gallbladder wall hypoplasia and liver damage in both mouse and human cases, these findings provide an insight into the critical role of SOX17-positive gallbladder walls in establishing functional bile duct networks in the hepatic hilus of neonates.
... DRs develop in many chronic liver diseases with different etiologies, where they show a strong correlation with the disease severity [7]. Cholangiopathies such as biliary atresia (BA), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and other chronic conditions such as alcoholic hepatitis (AH), nonalcoholic steatohepatitis (NASH), and viral hepatitis are some of the liver diseases associated with DRs [7][8][9][10][11][12][13][14][15][16]. The scientific knowledge of liver injury and regeneration mechanisms has increased exponentially in recent decades. ...
Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and immune cells. The underlying pathology of DRs leads to extensive tissue remodeling in chronic liver diseases. DR initiates as a tissue-regeneration mechanism in the liver; however, its close association with progressive fibrosis and inflammation in many chronic liver diseases makes it a more complicated pathological response than a simple regenerative process. An in-depth understanding of the cellular physiology of DRs and their contribution to tissue repair, inflammation, and progressive fibrosis can help scientists develop cell-type specific targeted therapies to manage liver fibrosis and chronic liver diseases effectively.
... It is universally fatal if not treated and is the most common identifiable cause of neonatal cholestasis and the leading indication for pediatric liver transplant. The etiology of BA remains elusive and is likely multifactorial in origin with contributing factors including exposure to viral or toxic pathogens in utero, immunologic mechanisms and possible predisposing genetic factors [24]. Biliary atresia may occur in isolation (70%), with laterality malformations (10% to 15%) also known as biliary atresia splenic malformation syndrome (BASM), or with other congenital anomalies (10% to 15%). ...
Purpose of Review
Cholestasis is characterized by a conjugated hyperbilirubinemia secondary to impaired bile synthesis, transport, or excretion from the liver. It is always pathologic and can be indicative of an underlying hepatobiliary, genetic, or metabolic disorder, several of which require timely diagnosis to ensure proper management and optimal outcomes. This review provides an overview of the evaluation of cholestasis with a focus on current and emerging treatment strategies.
Recent Findings
Increased accessibility of next generation sequencing (NGS) allows for utilization of genetic testing early in the diagnostic process. This may alter the clinical algorithm for diagnosis of cholestatic disorders. An enhanced understanding of the underlying pathophysiology may help guide future development of targeted therapies, such as ileal bile acid transporter (IBAT) inhibitors. These were recently approved for treatment of cholestatic pruritus in patients with Alagille syndrome and Progressive Familial Intrahepatic Cholestasis.
Summary
Current management of cholestasis is aimed at the biochemical consequences of impaired bile flow, including malnutrition, pruritus, and progressive fibrosis. NGS has led to an enhanced understanding of biliary pathology and may guide development of future treatment modalities based on specific gene mutations. Rapid discernment of the underlying etiology is essential as new treatment modalities emerge.
