Nuetrophil Elastase Mediated Damage in Infants with Extrahepatic Biliary Atresia: A Prospective Cohort Study

Background: Neutrophils are part of our innate immune system. They are capable of accumulation in tissues, chemotaxis, phagocytosis and digests bacteria and fungi by their lysosymes. Yet, paradoxically neutrophils are mediators in acute liver injury. Extrahepatic biliary atresia (EHBA) is a progressive chronic cholangiopathy of infancy, even in those who undergo timely portoenterostomy. Objective: Assessment of neutrophil involvement in EHBA. Subjects and Methods: 32 Infants known to have EHBA attendants of Hepatology Clinic, New Children Hospital, Cairo University, were enrolled in this study. It commenced by October, 1999 and ended by October, 2002. Percutaneous biopsied liver tissue (using Menghini needles) required for confirmation of diagnosis of extra-hepatic biliary atresia was assessed for fibrosis, neutrophil infiltration, neutrophil elastase and CD14+. Results: All biopsies (100%) demonstrated fibrosis of them 2 (6.3%) demonstrated cirrhosis. Neutrophil counts ranged from 2 to 12 cell per high power field (mean ± SD= 5.8±2.5). Anti-neutrophil elastase stained strong positive in all (100%) biopsies. All biopsies stained positive for CD 14+ where 24 (75%) demonstrated moderate and 8 (25%) strong staining. Strength of CD14+ staining correlated positively with neutrophil counts per high power field (p=0.0000), but not to fibrosis score ( p=0.252). CD14+ staining negatively correlated with cirrhosis (p=0.0000). Fibrosis score had a trend for positive correlation with neutrophil counts that did not mount to statistical significance ( p=0.065). Both did not predict favorable outcome (CD14+ p=0.356, fibrosis score p=0. 812) or deterioration (CD 14+ p=0. 13 1, fibrosis score p=0.584). Neutrophil elastase stain was strongly positive in all cases. Only predictors of good outcome in a multiregression model with 95% confidence interval was younger age at Kasai portoenterostomy (p=0.012) and less fibrosis (p=0.000). Conclusion: Neutrophil elastase is integral in liver histopathology in EHBA yet neutrophil exact role in tissue injury await exploration.