RELATIONSHIP BETWEEN THE SERUM ALANINE AMINOTRANSFERASE LEVEL AT THE END OF INTERFERON TREATMENT AND HISTOLOGIC-CHANGES IN WILD-TYPE AND PRECORE MUTANT HEPATITIS-B VIRUS-INFECTIONS

Unravelling the role of interferon (IFN) in the treatment of chronic h epatitis B is complicated by many factors, Several mutant forms of hep atitis B virus (HBV) have recently been discovered; the most common of these is the precore mutant, characterized by hepatitis Be antigen (H BeAg) negativity and hepatitis Be antibody (HBeAb) positivity in an in dividual with an active HBV infection, The aim of this study was to co mpare the response rate to IFN therapy in patients with wild-type HBV infection and in individuals infected with the precore mutant, A secon d aim was to evaluate the role of an increased serum ferritin in terms of the IFN response rate in these two different types of HBV infectio n,IFN therapy was administered at a dose of 5 MU subcutaneously three times weekly for 6 months to 41 individuals with a chronic wild-type h epatitis B infection and 16 individuals with a precore mutant chronic HBV infection, An IFN response was defined as normalization of the ser um alanine aminotransferase (ALT) level and an HBeAg to HBeAb seroconv ersion (in wild-type hepatitis infection), and a normalization of the serum ALT in individuals infected with a precore mutant infection, At entry, the two groups were matched for age, gender, serum ALT, serum i ron, total iron binding capacity (TIBC), serum ferritin and liver hist ology. Forty-six per cent of the subjects with wild-type disease respo nded to IFN therapy. By contrast, only four of the 16 cases (25%) of t he precore mutant cases responded (P < 0,05), Ferritin levels correlat ed well with the type of IFN response; as the serum ferritin level inc reased, the response rate to IFN declined, Hapatic infection caused by a precore HBV mutant is more resistant to IFN therapy than wild-type infection, The serum ferritin level appears to influence the type of I FN response achieved, Individuals with a serum ferritin level greater than 300 ng ml(-1) failed to respond to IFN in 93% of the cases studie d.