The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenterostomy is associated with the postoperative prognosis

Santos, Jorge Luiz dos; Kieling, Carlos Oscar; Meurer, Luíse; Vieira, Sandra Maria Gonçalves; Ferreira, Cristina Targa; Lorentz, Andrea Longoni; Silveira, Themis Reverbel da

doi:10.1016/j.jpedsurg.2008.09.013

Cited by 60 publications

(55 citation statements)

References 41 publications

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“…Specifically in the context of ACOL, this lack of association may be ascribed to inherent difficulties in the analysis of liver fibrosis, such as sampling errors and phenotypic idiosyncratic features in relation to fibrogenesis (2). The absence of correlation between the expression of ANGPTs and the extent of fibrosis goes against the supposition that the overexpression of these molecules in BA, and the associated MT, can be fully explained by increased levels of shear stress.…”

Section: Discussionmentioning

confidence: 99%

“…PCK7. PCK7 assessment was performed as described elsewhere (2). PCK7 was measured in pixels through the color range tool of the image analysis software, selecting a foreground color and a background color and then applying the Grow tool to amplify the spectrum of the color of interest so that the whole CK7-positive area was represented.…”

Section: Morphometric Calculationsmentioning

confidence: 99%

“…The primary treatment for BA is a hepatoportoenterostomy, which should be performed as soon as possible, because its chances of longterm success decrease when the age at surgery increases (1). In addition to age at portoenterostomy, histological findings observed in biopsies collected at the time of the procedure, such as the extents of fibrosis and ductular reaction, represent variables associated with disease severity and can help foresee the postoperative outcomes (2).…”

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confidence: 99%

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Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia

et al. 2013

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Background: Biliary atresia (BA) is an infantile disorder characterized by progressive sclerosing cholangiopathy leading to biliary obstruction. First-line treatment of BA is hepatoportoenterostomy, the prognosis of which is related to age at surgery and to histological variables such as extent of fibrosis and ductular reaction. Hepatic arterial medial thickening (MT) suggests an arteriopathy in BA pathogenesis. We evaluated the expression of angiopoietin (ANGPT)/tyrosine kinase with immunoglobulin-like and epidermal growth factorlike domains 2 (TIE2) system in liver samples obtained from patients with BA, correlating it with MT, variables associated with disease severity, and postoperative prognosis. Methods: ANGPT1, ANGPT2, and TIE2 expression levels were assessed by quantitative PCR in liver samples obtained from BA patients (n = 23) at portoenterostomy and age-matched infants with intrahepatic cholestasis (IHC; n = 7). Histological variables were morphometrically assessed. results: ANGPT1 and ANGPT2 were overexpressed in BA in comparison with IHC (P = 0.024 and P = 0.029, respectively). In BA, ANGPTs expression was positively correlated with MT (ANGPT1: r s = 0.59, P = 0.013; ANGPT2: r s = 0.52, P = 0.032), not with the variables associated with disease severity. TIE2 and ANGPTs expression levels were negatively correlated (ANGPT1: r s = −0.73, P < 0.001; ANGPT2: r s = −0.54, P = 0.007). conclusion: In BA, there is overexpression of both ANGPT1 and ANGPT2, which is correlated with MT but not with age at portoenterostomy or with the histological variables associated with disease severity at the time of procedure. Biliary atresia (BA) is an infantile hepatobiliary disorder characterized by the obstruction of bile ducts associated with a progressive sclerosing cholangiopathy. The primary treatment for BA is a hepatoportoenterostomy, which should be performed as soon as possible, because its chances of longterm success decrease when the age at surgery increases (1). In addition to age at portoenterostomy, histological findings observed in biopsies collected at the time of the procedure, such as the extents of fibrosis and ductular reaction, represent variables associated with disease severity and can help foresee the postoperative outcomes (2).Regardless of portoenterostomy, BA induces cirrhosis by the continuous sclerosing cholangiopathy process, thus making this entity the leading cause of liver transplantation in children.The etiology of such a cholangiopathy remains elusive, and BA seems to represent more a phenotype than a unique disease. Our group is interested in the putative role of an arteriopathy in the development of BA because there are arteriographic (3), ultrasonographic (4-6), computed tomographic (7), histological (8), and immunohistochemical (9) evidences of medial thickening (MT) in hepatic artery branches owing to a vascular remodeling associated with hypoxia-ischemia in the portal tracts and porta hepatis. Knowledge on the behavior of angiogenic molecules in the liver of the affected patients...

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Section: Discussionmentioning

confidence: 99%

Section: Morphometric Calculationsmentioning

confidence: 99%

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confidence: 99%

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Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia

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“…In the first study, the investigators quantified the proliferation of bile ducts by morphometric analysis of the percentage of CK7-positivity (PCK7) in livers of patients with BA at the time of portoenterostomy. PCK7 correlated with a poor postoperative prognosis, suggesting that it might serve as a histological predictor of clinical course (26). There is increasing evidence that cholangiocytes may be an important source of fibrogenesis either indirectly by activating fibrogenic cells through cytokine release, or directly by tilting the balance toward matrix accumulation.…”

Section: Epithelial-mesenchymal Transition In the Pathogenesis Of Thementioning

confidence: 99%

Advances in biliary atresia: from patient care to research

Santos

Carvalho²,

Bezerra

2010

Braz J Med Biol Res

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“…In all patients in whom whitecolored stool continues, liver biopsy should be performed. In all patients in whom liver biopsy reveals new bile duct formation and bile thrombi, the definite diagnosis should be made by performing "peroperatory" or "percutaneous" cholangiography (11). Biliary atresia requires surgical intervention during the first 2 months of life.…”

Section: Introductionmentioning

confidence: 99%

Yenidoğan ve süt çocukluğunda kolestaz

Çokuğraş¹,

Beşer²

2012

tpa

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Review Sum maryDuring the newborn and infancy period, it is an important to demonstrate the condition which causes cholestatic liver diseases. If direct bilirubin level is more than 20% of total biluribin, it is defined as cholestasis. Especially early diagnosis of diseases including biliary atresia, tyrosinaemia, galactosemia is crucial for prevention of permanent damage in the future and for benefit from early treatment. Therefore, total, direct and indirect bilirubin levels should be measured in all newborns with jaundice lasting longer than two weeks. If 20% of total bilirubin is direct bilirubin, liverrelated disorders should be questioned. In this review, we aimed to show which clinical and laboratory features should be considered to demonstrate the cause of cholestatic diseases. (Turk Arch Ped 2012; 47: 1-7)

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The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenterostomy is associated with the postoperative prognosis

Cited by 60 publications

References 41 publications

Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia

Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia

Advances in biliary atresia: from patient care to research

Yenidoğan ve süt çocukluğunda kolestaz

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