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
Background Rare disease Incidence 1 in 5000 1 in 20 000 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
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
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
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: 21 102 d) 33% 67% Age in days
Results Survival distribution function Mortality: 45.8% 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 10 20 30 40 50 60 70 Serial time (months)
Results Intra-operative histology Degree of fibrosis: According to METAVIR grading
Results Intra-operative histology Bile duct hyperplasia
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%
Results 14 12 13 CMV serology 10 8 9 6 4 3 2 0 Nr of patients CMV + CMV Exposed CMV -
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 = 0.059 p-value = 0.757 140 120 100 80 60 40 20 0-1 0 1 2 3 4 5-20 Liver fibrosis CAT
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)
Relationship between bile duct hyperplasia and outcome 1 0.9 0.8 0.7 0.6 0.5 Survival distribution function No statistically significant relationship between degree of bile duct hyperplasia and outcome P-value: 0,204 0.4 0.3 0.2 0.1 0 0 5 10 15 20 25 30 35 40 45 50 Serial time (months) Key: 1 = No/Mild Bile duct hyperplasia 2 = Moderate/Severe bile duct hyperplasia 1 2
Results Bile ductule size and outcome Bile ductule size at portal plate: <100 700 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
CMV serology CAT Relationship between CMV serology and degree of fibrosis 6 5 Pearson co-efficient = 0.124 P-value: 0,513 4 3 2 1 0-1 0 1 2 3 4 5-1 Liver fibrosis CAT
Relationship between CMV serology and outcome Key: 1 = CMV+ 2 = CMV exposed, but negative 1 0.9 0.8 0.7 0.6 0.5 0.4 Survival distribution function of CMV Positive vs CMV negative patients 0.3 P-value: 0.518 0.2 0.1 0 0 10 20 30 40 50 60 70 Serial time (months) 1 2
Conclusion Survival distribution function In our study population, there was a high mortality rate after KPE. 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 10 20 30 40 50 60 70 Serial time (months)
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.
Conclusion CMV positive patients had a significantly earlier mortality compared to CMV exposed patients No statistically significant effect on long-term outcomes.
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Acknowledgements Thank you to Dr De Maayer for the use of his Biliary Atresia database.
Thank you for your attention