Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

Abstract

Background. Autotaxin (ATX) is a secreted glycoprotein that is involved in the development of hepatic fibrogenesis via the enzymatic production of lysophosphatidic acid. The aim of this study was to investigate hepatic expression of ATX in biliary atresia (BA) compared with non-BA liver controls and to examine the association between ATX expression and clinical outcome in BA. Methods. Liver specimens from BA infants (n=20) were compared with samples from infants who underwent liver biopsy for reasons other than BA (n=14) served as controls. Relative mRNA and protein expression of ATX were quantified using real-time polymerase chain reaction (PCR) and immunohistochemistry. Masson's Trichrome staining was performed to determine the degree of liver fibrosis. Results. Quantitative real-time PCR demonstrated overexpression of ATX mRNA in BA livers. In immunohistochemical evaluation, ATX was positively stained on the hepatic parenchyma and the biliary epithelium in BA patients, as compared to non-BA controls. The immunostaining score of ATX in BA livers was also significantly higher than that observed in non-BA livers (P<0.001). Subgroup analysis revealed that ATX expression in the patients with poor outcome was significantly greater than in those with good outcome (P=0.03). Additionally, there was a positive correlation between hepatic ATX expression and Metavir fibrosis stage in BA livers (r=0.79, P<0.001). Discussion. This study found that mRNA and protein expression of ATX was increased in BA livers. High hepatic ATX expressionat the time of Kasai operation was associated with liver fibrosis and outcome in BA, suggesting that ATX may serve a role as a promising biomarker of the prognosis in biliary atresia.