Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response.
Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Scully
L J
LJ
Academic Department of Medicine, Royal Free Hospital, Hampstead, London, England.
Brown
D
D
Lloyd
C
C
Shein
R
R
Thomas
H C
HC
D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D002908:Chronic Disease; D005260:Female; D005544:Forecasting; D006509:Hepatitis B / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D007372:Interferons / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged
D007372:Interferons