Currently no
therapy is given to patients with
chronic hepatitis B virus (HBV)
infection who are
HBeAg positive with normal
alanine aminotransferase (ALT) levels.
Steroid priming has been shown to enhance T-helper-1 (Th-1) cell response.
Lamivudine may restore immunologic competence against HBV by causing a sudden decline in the level of the virus. We examined the efficacy of
lamivudine pulse
therapy on the seroconversion from
HBeAg to anti-HBe. This was a prospective single-blinded trial including 27 patients with
chronic hepatitis B,
HBeAg positive with ALT < or =1.5 times upper limit of normal (ULN).
Lamivudine was administered initially for 4 weeks, then stopped for 2 weeks and later restarted and continued till 3 months after seroconversion or completion of 2 years of
therapy. Twenty-six patients completed the study.
Lamivudine withdrawal led to a rise in ALT levels above the ULN in 11 (42.3%) patients at 6 weeks; seven of them (63.6%) lost
HBeAg compared with only two of the 15 patients (13.3%), in whom ALT levels did not rise (P = 0.011). As one patient showed a relapse, a total of eight (31%) patients responded to
lamivudine pulse
therapy over a mean period of 17.3 +/- 4.5 months. Responders had a higher
serum albumin (P < 0.05), a lower
fibrosis score (P < 0.05), and a relatively high baseline serum ALT levels (P = 0.024) than the nonresponders. YMDD mutations developed in three patients and none responded. No patient developed hepatic decompensation. Hence
lamivudine pulse
therapy has potential in converting
HBeAg-positive, 'not-treat-worthy' (ALT < 1.5 ULN) patients to treat-worthy (ALT > 1.5 ULN) in 42%, with sustained
HBeAg and HBV
DNA loss in 31% patients. The effects are possibly because of a combination of
antiviral and immunomodulating activities of
lamivudine.