Diagnostic value of hepatic intercellular adhesion molecule‐1 expression in Egyptian infants with biliary atresia and other forms of neonatal cholestasis

Ghoneim, Elham M.; Sira, Mostafa Mohamed; Elaziz, Azza M. Abd; Khalil, Fatma Omar; Sultan, Mervat M.; Mahmoud, Ahmed B

doi:10.1111/j.1872-034x.2011.00832.x

Cited by 16 publications

(14 citation statements)

References 36 publications

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“…Importantly, the staining pattern of YAP is both strong and diffuse. YAP staining also appears to be the most sensitive and specific IHC markers tested as ancillary tools in the differential diagnosis of BA versus non-BA neonatal cholestasis 9,11,12 . The extent and intensity of YAP expression appears to be highly dependent on the clinical situation.…”

Section: Discussionmentioning

confidence: 99%

“…General epithelial markers such as CK7 and CK19 stain biliary epithelium but not the newly emergent, proliferating bile ductules 10 . Alternatively, neural cell adhesion molecule (NCAM/CD56) 9 and intercellular adhesion molecule 1 (ICAM-1) 12 can stain both the existing bile ducts and the newly-formed bile ductules, but mark these bile ductules in a somewhat weak and non-specific fashion. The cytoplasmic/membranous staining pattern of both markers can be difficult to optimize and interpret.…”

Section: Introductionmentioning

confidence: 99%

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The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease

et al. 2014

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Although physiologic jaundice of neonates is common, persistent neonatal cholestasis is life-threatening and has multiple etiologies. Among these etiologies, biliary atresia (BA) requires rapid diagnosis and treatment. In diagnosing BA, the surgical pathologist must recognize subtle histologic changes, often with only a small core liver biopsy. To aid in the differential diagnosis of neonatal cholestasis, we investigated Yes-associated protein (YAP), a regulator of organ size and bile duct development. We examined whether a YAP immunostain can highlight emerging hepatobiliary epithelium in BA [n=28] versus other causes of persistent cholestasis (non-BA) [n=15] and thus serve as a useful diagnostic marker in persistent neonatal jaundice. We show significantly (p≤0.01) more high-grade (≤2) fibrosis and ductular proliferation among BA versus non-BA cases. Likewise, there was significantly more high-grade (2–3/3) cytoplasmic and nuclear YAP staining in BA (97% and 89%) versus non-BA (20% and 13%). High-grade nuclear YAP staining was both sensitive (88%) and specific (87%) for the diagnosis of BA. In contrast to neonatal cholestasis, the differences in YAP localization in cholestatic/obstructed vs. non-obstructed adult livers were not significant. Lastly, we found that pharmacological inhibition of the YAP complex in both cholangiocyte and cholangiocarcinoma cell lines blocked compensatory bile duct proliferation, an early marker of BA that requires nuclear YAP expression, in a time- and dose-dependent manner. In summary, we show that YAP expression modulates both bile duct proliferation and liver damage/fibrosis while acting as a sensitive and specific marker in the differential diagnosis of persistent neonatal cholestasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease

et al. 2014

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“…Importantly, ICAM-1 expression has previously been shown to be upregulated within BA liver tissue[51] and a recent study from Egypt identified elevated sICAM-1 levels in BA patients compared to controls. [52] In addition, analysis of polymorphisms of the ICAM-1 gene in BA discovered that the ICAM G241R polymorphism was significantly associated with BA, suggesting that this polymorphism plays a role in disease pathogenesis. [53] ICAM-1 is an adhesion molecule that is expressed on cells of multiple lineages at sites of inflammation and mediates leukocyte and granulocyte migration through endothelial cells as well as promotes antigen-specific T cell proliferation.…”

Section: Evidence For Dysregulation Of Adaptive Immunity In Biliary Amentioning

confidence: 99%

Biliary atresia: cellular dynamics and immune dysregulation

Feldman

Mack

2012

Seminars in Pediatric Surgery

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The cause of biliary atresia (BA) is unknown and in the past few decades the majority of investigations related to pathogenesis have centered on virus infections and immunity. The acquired or perinatal form of BA entails a progressive, inflammatory injury of bile ducts, leading to fibrosis and obliteration of both the extrahepatic and intrahepatic bile ducts. Theories of pathogenesis include viral infection, chronic inflammatory or autoimmune-mediated bile duct injury and abnormalities in bile duct development. This review will focus solely on human studies pertaining to a potential viral trigger of bile duct injury at diagnosis and provide insight into the interplay of the innate and adaptive immune responses in the pathogenesis of disease.

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“…We have previously studied different proinflammatory molecules such as intercellular adhesion molecule-1 [6], CD56 [7], and P-selectin [8] and different proinflammatory cytokines such as IL-2 and IL-8 [9] in BA and described their relation to the disease process.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Serum IL-12p40 Is a Potential Predictor of Kasai Portoenterostomy Outcome in Infants with Biliary Atresia

Goda

Khedr

El-Shenawy

et al. 2017

Gastroenterology Research and Practice

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The standard-of-care treatment for biliary atresia (BA) is surgical restoration of bile flow by Kasai portoenterostomy. We aimed to study serum interleukin- (IL-) 12p40, a natural antagonist for the proinflammatory IL-12p70, and its relation to surgical outcomes of BA. The study included 75 infants with neonatal cholestasis: BA group (n = 25), non-BA cholestasis group (n = 30), and neglected BA group (n = 20), in addition to thirty healthy neonates serving as controls. IL-12p40 was measured by ELISA in all individuals and a second assessment was performed 3 months postoperatively in the BA group. The surgical outcomes were classified as successful (bilirubin ≤ 2 mg/dl) or failed (bilirubin > 2 mg/dl). IL-12p40 was higher in BA compared to that in the non-BA and control groups (P values were 0.036 and <0.0001, resp.) but comparable to that in the neglected BA group. Preoperative IL-12p40 levels in BA patients were significantly higher in successful Kasai compared with failed Kasai and a cutoff level of 547.47 pg/ml could predict the successful outcome with 87.5% sensitivity and 82.4% specificity. Three-month postoperative IL-12p40 tended to decrease in both the successful and failed groups. In conclusion, preoperative serum IL-12p40 is a potential predictor of Kasai outcome. Serial postoperative measurements may anticipate the failure of an initially successful operation, hence the need for liver transplantation.

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Diagnostic value of hepatic intercellular adhesion molecule‐1 expression in Egyptian infants with biliary atresia and other forms of neonatal cholestasis

Abstract: These results suggest that ICAM-1 has a diagnostic value in patients with BA and would be a promising helpful tool when investigating patients with NC.

Cited by 16 publications

References 36 publications

The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease

The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease

Biliary atresia: cellular dynamics and immune dysregulation

Preoperative Serum IL-12p40 Is a Potential Predictor of Kasai Portoenterostomy Outcome in Infants with Biliary Atresia

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