PROGRESS IN DEVELOPING ANIMAL-MODELS FOR BILIARY ATRESIA

Animal models for extrahepatic biliary atresia (EHBA) have failed to s imulate the course of the disease, Until now only a few aspects of the entity could be investigated and no model was helpful in discovering the etiology of EHBA. Following the suspicion of a viral and hepatotro pic infection, investigations in an infectious mouse model were contin ued. The results of previous and topical studies are summarized here, Infection of newborn Balb/c-mice with rhesus rotavirus (RRV) leads to cholestasis in 85% of the animals followed by a lethality of 90%, Prep aration and histomorphological investigation of liver and ligamentum d uodenale reveal EHBA of varying extent. Clinical course and morphologi cal findings in mice are very similar to EHBA in newborn children and the results are presented in a chronological table, Hepatobiliary morb idity and lethality after RRV infection is higher in Balb/c-mice than in other mouse strains. This observation supports the suspicion that i mmunocompetence might be a determining factor in the etiology of EHBA. Initial therapeutic trials were made using this model by treating inf ected newborn mice with interferon-cl (IFN). The prophylactic applicat ion of IFN protects the infected mice from cholestatic symptoms and ap pears to induce partial immunity, Their descendants are protected agai nst the hepatotropic effect of RRV infection, Infected animals present ing with clinical signs of cholestasis can be treated successfully by IFN-therapy for one week. In the presented animal model, EHBA can be b etter induced and simulated than by any other method. As a first trial , a non-surgical and more etiologically orientated therapeutic method is tested in this model.