Biliary Atresia Animal Models: Is the Needle in a Haystack?

Abstract

Biliary atresia (BA) is a progressive fibro-obliterative process with a variable degree of inflammation involving the hepatobiliary system. Its consequences are incalculable for the patients, the affected families, relatives, and the healthcare system. Scientific communities have identified a rate of about 1 case per 10,000-20,000 live births, but the percentage may be higher, considering the late diagnoses. The etiology is heterogeneous. BA, which is considered in half of the causes leading to orthotopic liver transplantation, occurs in primates and non-primates. To consolidate any model, (1) more transport and cell membrane studies are needed to identify the exact mechanism of noxa-related hepatotoxicity; (2) an online platform may be key to share data from pilot projects and new techniques; and (3) the introduction of differentially expressed genes may be useful in investigating the liver metabolism to target the most intricate bilio-toxic effects of pharmaceutical drugs and toxins. As a challenge, such methodologies are still limited to very few centers, making the identification of highly functional animal models like finding a "needle in a haystack". This review compiles models from the haystack and hopes that a combinatorial search will eventually be the root for a successful pathway.

Keywords: animal model; biliary atresia; congenital; liver; perinatal.

Figure 1

Experimental biliary atresia with fibrosis and bile duct proliferation of biliary epithelial cells in the portal tracts is evidenced by immunohistochemistry with an antibody against keratin 7 (intermediate filament of the cytoskeleton) (x200 as original magnification). An experimental biliary atresia may be setup with several laboratory animals with lines of scientific progress of this and last centuries toward viral, surgical, toxin-based, and genetic animal models.