A review of histological parameters and CMV serology in Biliary atresia, and its relationship to long-term outcomes
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1 A review of histological parameters and CMV serology in Biliary atresia, and its relationship to long-term outcomes DR A. WITHERS, DR A. GRIEVE DEPARTMENT OF PAEDIATRIC SURGERY UNIVERSITY OF THE WITWATERSRAND JOHANNESBURG 11 NOVEMBER 2017
2 Background Rare disease Incidence 1 in in live births 1 Progressive, obliterative cholangiopathy 2 -> affects intra-, and extra-hepatic bile ducts to varying degrees Pathogenesis: Unknown Most likely multi-factorial Genetic factors Environmental toxins Viruses CMV, Reovirus, Rotavirus, Papilloma virus, EBV 2 6
3 Background Management: KPE Many will require liver Tx Prognosis Currently leading indication for liver Tx in children 7 Factors implicated in affecting prognosis Age of pt at KPE 8 Histological features Degree of liver fibrosis 1,8 10 Size of bile ductules 10 Co-infection with CMV 2,3,4
4 Aims and Methods Aims: Describe the patient demographic of patients presenting to CMJAH and CHBAH with Biliary atresia Describe the long-term outcomes of these patients To review Liver histology at the time of KPE, and it s effect on outcome Methods: To review the prevalence of CMV co-infection in our population at the time of KPE, and to investigate its effect on outcome. Retrospective review of patients who presented with Biliary Atresia between 2009 and 2012 Patients selected from established database Review of patient demographics Intra-operative histology CMV serology Outcomes
5 Results 43 patients 11 patients excluded due to inadequate or missing histology specimens or where long-term outcomes were unknown GENDER Male Female Age at KPE Mean: 61 days (Range: d) 33% 67% Age in days
6 Results Survival distribution function Mortality: 45.8% Serial time (months)
7 Results Intra-operative histology Degree of fibrosis: According to METAVIR grading
8 Results Intra-operative histology Bile duct hyperplasia
9 Results Intra-operative histology PRESENCE OF BILE PLUGS ON HISTOLOGY Absent Present Bile lake formation Unknown CHOLESTASIS PRESENT Mild Moderate Severe Unknown 3% 7% 20% 37% 33% 57% 3% 40%
10 Results CMV serology Nr of patients CMV + CMV Exposed CMV -
11 Age at KPE in days Relationship between age at KPE and degree of fibrosis 160 No correlation between age at KPE and degree of fibrosis Pearson s r coefficient = p-value = Liver fibrosis CAT
12 Relationship between degree of fibrosis and outcome Improved survival in patients with no/mild fibrosis at the time of KPE compared to pattients with Gr3 fibrosis/cirrhosis, However, not statistically significant. P-value: 0,324 Key (According to METAVIR grade): 1 = No fibrosis/mild Fibrosis (METAVIR Gr 0 /1 / 2) 2 = Severe bridging fibrosis/cirrhosis (METAVIR GR 3 / 4)
13 Relationship between bile duct hyperplasia and outcome Survival distribution function No statistically significant relationship between degree of bile duct hyperplasia and outcome P-value: 0, Serial time (months) Key: 1 = No/Mild Bile duct hyperplasia 2 = Moderate/Severe bile duct hyperplasia 1 2
14 Results Bile ductule size and outcome Bile ductule size at portal plate: < μm Mean: 0,359 μm No statistically significant correlation between bile duct size and outcome Pearson s co-efficient = 0,048 P-value: 0,887
15 CMV serology CAT Relationship between CMV serology and degree of fibrosis 6 5 Pearson co-efficient = P-value: 0, Liver fibrosis CAT
16 Relationship between CMV serology and outcome Key: 1 = CMV+ 2 = CMV exposed, but negative Survival distribution function of CMV Positive vs CMV negative patients 0.3 P-value: Serial time (months) 1 2
17 Conclusion Survival distribution function In our study population, there was a high mortality rate after KPE Serial time (months)
18 Conclusion There was no clear correlation between Age of KPE and degree of fibrosis. Age, degree of fibrosis, degree of bile duct hyperplasia, Bile duct size did not show any statistically significant correlation with outcomes.
19 Conclusion CMV positive patients had a significantly earlier mortality compared to CMV exposed patients No statistically significant effect on long-term outcomes.
20 References 1. Czubkowski P, Cielecka-Kuszyk J, Rurarz M, Kamińska D, Markiewicz-Kijewska M, Pawłowska J. The limited prognostic value of liver histology in children with biliary atresia. Annals of Hepatology. 2015;14(6): Lopez R, Ooi C, Krishnan U. Early and Peri-operative Prognostic Indicators in Infants Undergoing Hepatic Portoenterostomy for Biliary Atresia: a Review. Current Gastroenterology Reports. 2017;19(4). 3. Rauschenfels S, Krassmann M, Al-Masri A, Verhagen W, Leonhardt J, Kuebler J et al. Incidence of hepatotropic viruses in biliary atresia. European Journal of Pediatrics. 2008;168(4): Schukfeh N, Al_Glamrah A, Petersen C, Kuebler JF. Detection of hepatotropic viruses has no impact on the prognosis after Kasai procedure. J Pediatric Surgery. 2012;47(10): Bessho K, Bezerra J. Biliary Atresia: Will Blocking Inflammation Tame the Disease?. Annual Review of Medicine. 2011;62(1): Selmi C, Vergani D, Mieli-Vergani G. Viruses and Autoantibodies in Biliary Atresia. Gastroenterology. 2010;139(5): Chardot C, Buet C, Serinet M, Golmard J, Lachaux A, Roquelaure B et al. Improving outcomes of biliary atresia: French national series Journal of Hepatology. 2013;58(6):
21 References 8. Roy P, Chatterjee U, Ganguli M, Banerjee S, Chatterjee S, Basu A. A histopathological study of liver and biliary remnants with clinical outcome in cases of extrahepatic biliary atresia. Indian Journal of Pathology and Microbiology. 2010;53(1): Davenport M, Puricelli V, Tizzard S, Farrant P, Hadzic N, Mieli-Vergani G et al. The outcome of older infants (100 days+) with biliary atresia. Journal of Hepatology. 2002;36: Zhang S, Wu Y, Liu Z, Tao Q, Huang J, Yang W. Hepatic pathology of biliary atresia: A new comprehensive evaluation method using liver biopsy. The Turkish Journal of Gastroenterology. 2016;27(3):
22 Acknowledgements Thank you to Dr De Maayer for the use of his Biliary Atresia database.
23 Thank you for your attention
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