Interferon treatment in acute progressive and fulminant hepatitis

A small proportion of patients with acute viral hepatitis run a progressive fulminant course ending in acute liver failure with encephalopathy, and with a mortality rate of 75-80%. In small children and pregnant women mortality is even higher. We have treated 32 patients of all ages with acute progressive and fulminant hepatitis over the last 7 years in an uncontrolled trial with human interferon-alpha (HulFN-alpha), with i.m. doses of 3 x 10(6) u/day (70,000 u/kg per day for infants) for 8 +/- 3 days (mean +/- SD.) In 17 patients hepatitis was due to hepatitis A virus, in 7 to hepatitis B virus, in 6 to non A-non B virus and in 1 case each to herpes and cytomegalovirus. Sixteen patients (50%) recovered including 9 of 22 (41%) who were in Grades III-IV coma when treatment was started. Only 1 of 8 children less than 4 years of age recovered, whereas 15 of 24 (62%) older children and adults survived. Two of three pregnant women with acute fulminant hepatitis survived. In patients who recovered, improvement was often noted on about the fifth day of IFN treatment: 9 of 16 patients died before completing 5 days of therapy. Our studies of the IFN system response to hepatitis viruses showed that the greater majority of patients produce IFN in the acute stage of the infection. However, a minority have a defective IFN response that is more severe and more common in progressive fulminant hepatitis, and in several of these patients IFN response was completely lacking. It is in these cases that IFN treatment is likely to have the greatest value. On the basis of these encouraging preliminary results, it is suggested that a well-controlled, double-blind study be done to evaluate the effectiveness of HulFN-alpha treatment when given early during the course of acute progressive viral hepatitis.