Treatment of extrahepatic biliary atresia with interferon-alpha in a murine infectious model.
The etiology of extrahepatic biliary atresia (EHBA) in newborns remains unknown, although a first infectious animal model with complete obstruction of the common bile duct could be established. Intraperitoneal inoculation of newborn Balb/c mice with rhesus rotavirus induced cholestasis, 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 investigated in this animal model. Single-dose therapy with 10000 IU of IFN-alpha protected all rhesus rotavirus-infected pups from cholestatic disease. The same dose, injected 5 d after infection, had no protective effect. Starting with onset of cholestatic symptoms, the treatment with 10000 IU of IFN-alpha daily showed good results in 29 mice. Seventy-six percent of the mice recovered after 1 wk of therapy. Histologic investigation revealed normal findings in the hepatobiliary tract of clinically normal mice. Twenty-one percent of the descendants of infected and prophylactic IFN-alpha-treated mice showed cholestatic symptoms after infection with rhesus rotavirus (79% in an untreated control group) and a milder form of the illness. In conclusion, we found that prophylactic treatment with IFN-alpha prevented the hepatobiliary system of newborn Balb/c mice from severe damage by rhesus rotavirus in this artificially designed infectious model for EHBA. Infected and icteric mice, treated for 1 wk with IFN-alpha, had good prospects for recovery and prevention of complete and irreversible occlusion of the extrahepatic bile ducts. Infected and prophylactic IFN-alpha-treated dams gave good protection to their descendants. This means that EHBA in this model could probably be averted by maternal antibodies against rotavirus.
Petersen
C
C
Department of Pediatric Surgery, Medical School of Hannover, Germany.
Bruns
E
E
Kuske
M
M
von Wussow
P
P
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001656:Biliary Atresia / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D016898:Interferon-alpha / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D012400:Rotavirus Infections / Q000150:complications*
D000998:Antiviral Agents; D016898:Interferon-alpha