TREATMENT OF EXTRAHEPATIC BILIARY ATRESIA WITH INTERFERON-ALPHA IN A MURINE INFECTIOUS MODEL

The etiology of extrahepatic biliary atresia (EHBA) in newborns remain s unknown, although a first infectious animal model with complete obst ruction of the common bile duct could be established. Intraperitoneal inoculation of newborn Balb/c mice with rhesus rotavirus induced chole stasis, leading, in most cases, to biliary atresia with lethal outcome , similar to EHBA in human newborns. The influence of interferon-alpha (IFN-alpha) on the hepatotropism of rotavirus infection was investiga ted in this animal model. Single-dose therapy with 10 000 IU of IFN-al pha protected all rhesus rotavirus-infected pups from cholestatic dise ase. The same dose, injected 5 d after infection, had no protective ef fect. Starting with onset of cholestatic symptoms, the treatment with 10 000 IU of IFN-alpha daily showed good results in 29 mice. Seventy-s ix percent of the mice recovered after 1 wk of therapy. Histologic inv estigation revealed normal findings in the hepatobiliary tract of clin ically normal mice. Twenty-one percent of the descendants of infected and prophylactic IFN-alpha-treated mice showed cholestatic symptoms af ter infection with rhesus rotavirus (79% in an untreated control group ) and a milder form of the illness. In conclusion, we found that proph ylactic treatment with IFN-alpha prevented the hepatobiliary system of newborn Balb/c mice from severe damage by rhesus rotavirus in this ar tificially designed infectious model for EHBA. Infected and icteric mi ce, treated for 1 wk with IFN-alpha, had good prospects for recovery a nd prevention of complete and irreversible occlusion of the extrahepat ic bile ducts. Infected and prophylactic IFN-alpha-treated dams gave g ood protection to their descendants. This means that EHBA in this mode l could probably be averted by maternal antibodies against rotavirus.