Histological evidence of hepatitis-B-virus infection with negative serology in children with acute leukaemia who develop chronic liver disease.

A high percentage of patients with acute leukaemia in established remission develop chronic liver disease: how important hepatitis-B-virus (HBV) infection is as an aetiological factor is not clear. The presence of HBV markers in liver and serum of 23 leukaemic children with liver disease was investigated at the time of a diagnostic biopsy just before treatment withdrawal. Although, at this time, none had HBV antigens or antibodies in the serum by radioimmunoassay, HBsAg was detected by direct immunofluorescence in the cytoplasm of hepatocytes in 13 children, 7 of whom also had hepatitis-B core or e antigens in hepatocyte nuclei. This pattern of both cytoplasmic and nuclear fluorescence was present in 4 of 6 patients with the histological features of chronic active hepatitis on liver biopsy. The failure of release of viral antigens into serum and the absence of an adequate immune response were probably due to the intense chemotherapy used to induce and maintain remission, since HBV markers appeared in the serum within 15 months of stopping treatment in 8 of the children in whom viral antigens had been detected in liver tissue but in none of those whose biopsy specimens were negative by immunofluorescence. These results suggest that HBV infection may be an important cause of chronic liver disease in children with leukaemia and show that during treatment serological tests may fail to detect the presence of the virus.