الفهرس 
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Abstract
Summary
Extrahepatic biliary atresia (EHBA), characterized by obliteration or discontinuity of extrahepatic bile ducts, is still the major cause for LT among children nowadays. Despite the amount of effort put in by researchers worldwide, KPE and its modifications – is the only available treatment. All untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo LT.
The exchange and diffusion of information that can make the diagnosis of EHBA easier is of utmost importance, since prognosis is improved when patients are surgically treated by KPE in the first 2 months of life.
The main target of the current study was to study the expression of integrin β8 in patients with BA and compare it to patients with cholestasis due to other causes & correlate with degree of fibrosis .
The integrins are a group of cell adhesion molecules, which are capable of binding to and activating latent TGF-β complexes, interestingly, integrin ανβ8 activation of TGF-β is influenced by interactions with matrix metalloproteinase-14 (MMP) and likely other MMPs, which are also dysregulated in human BA and animal models.
This study included 30 infants with BA and another 30 infants with NC other than BA attending the Pediatric Hepatology Department, National Liver Institute, Menoufia University .
All patients underwent full history taking thorough clinical examination, and the following investigations:
1-CBC
2-Liver function tests (serum bilirubin total and direct, total protein, serum albumin, alanine aminotransferase, aspartate transaminase, ALKP and GGT).
3-Prothrombin time, concentration and INR.
4-Abdominal ultrasonography.
5-Duodenal tube aspiration (for some patients only).
7-Liver biopsy for all studied patients for pathological assessment.
7-Immunostaining of integrin-β8 antibody on paraffin embedded liver tissue from all cases included in this study.
Data were collected, coded and processed by statistical analysis using SPSS program version 21 and the results were put in tables and graphs.
Our results showed that:
1- BA and non-BA groups were age and sex matched (P >0.05).
2- The occurrence of clay stool was significantly higher in BA group than that in non-BA group (P <0.0001).
3- There was no statistical significant difference in body weight, length and HC between BA and non-BA groups (P > 0.05).
4- Abdominal examination showed that BA infants had hepatomegaly and splenomegaly (86.6%, 26.6% respectively), with no statistical significant difference to the non-BA group (80%, 20% respectively) (P > 0.05 ( .
5- Abnormal GB sonography (non-contractile or atretic) was significantly higher in the BA group (56.7% & 40% respectively) than that in the non -BA group (P <0.0001).
6- Subcapsular flow was statistically significant higher in BA group than in non-BA group with P-value < 0.05 .
7- Cardiac anomaly was not significantly different between BA groups and non- BA group with P-value > 0.05.
8- Duodenal tube aspiration was statistically significant higher in BA group than in non-BA group with p-value < 0.05.
9- As regard liver function tests (total and direct bilirubin, albumin, AST, ALT, ALP, PC) in our study, the mean serum levels were elevated in both groups with no significant difference between BA group and non- BA group.
10- GGT was statistically significantly higher in BA group than that in non BA group (P < 0.0001 (
11- Ductular proliferation and bile plugs were statistically significantly higher in BA group than that in non-BA group (P < 0.0001 .(
12- Liver fibrosis was statistically significant higher in BA group than in non-BA group with P-value <0.0001.
13- Integrin B8 IHC was statistically significant between BA, Non-BA and control group P-value < 0.05.
14- Positive correlation between Integrin B8 IHC and GGT , INR , Degree of portal ductal proliferation, Degree of portal portal bridging and stage of liver fibrosis in diseased groups (P <
0.05), while there was no significant correlation as regard IHC and other parameters (P > 0.05 (
15- Integrin B8 IHC was statistically significant in different stages of liver fibrosis with P-value < 0.05.
16- Integrin B8 IHC score at a cutoff value > 2 could discriminate between BA and non-BA groups had 0.729 AUROC with 83.3% sensitivity, 60% specificity, 67.6% PPV and 78.3% NPV.
17- Integrin B8 IHC score AUROC of 0.729 is indicative of a predictive biomarker to differentiate between BA group and non-BA group.
18- Combination of both cutoff values of integrin B8 IHC score > 2 and GGT > 280 are more specific to discriminate between BA and non-BA groups with specificity 86.7%.