Yf. Liaw et al., Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine therapy in patients with chronic hepatitis B, HEPATOLOGY, 32(3), 2000, pp. 604-609
Asian lamivudine trial has shown that hepatitis B e antigen (HBeAg) serocon
version rate during 1 year of lamivudine therapy was only 16% but was 64% i
n the subgroup of patients with a pretherapy serum alanine transaminase (AL
T) level over 5 times the upper limit of normal (ULN). To test whether ALT
rebound following corticosteroid priming enhances response to lamivudine th
erapy, a pilot study was conducted in 30 patients with ALT levels less than
5 x ULN (43-169; N < 36 U/L), They received 30 mg of prednisolone daily fo
r 3 weeks, 15 mg daily for 1 week, no treatment for 2 weeks, and then 150 m
g of lamivudine daily for 9 months. Complete response (CR) was defined as A
LT normalization with HBV-DNA seroclearance and HBeAg seroconversion. Perip
heral blood mononuclear cell proliferation and cytokine secretion in respon
se to recombinant HBV core antigen were serially assayed in 7 patients duri
ng priming and after withdrawal of prednisolone, Clinical rebound with an A
LT over 5 x ULN was observed in 20 patients (67%), Of these 20, 12 (60%) sh
owed CR as compared with 1 (10%) of the 10 patients without significant ALT
rebound (P < .002), The HBeAg seroconversion sustained in 70% of the patie
nts 3 to 6 months after the end of lamivudine therapy, Immunological assays
revealed that the responders showed Th1 dominant response and higher stimu
lation index to prednisolone priming. No serious side effect was encountere
d, These results suggest that corticosteroid priming induced immune/ALT reb
ound greatly enhances response to lamivudine therapy in chronic hepatitis B
, Confirmation by randomized controlled trial is needed.