Beneficial effects of 'lamivudine pulse' therapy in HBeAg-positive patients with normal ALT*.
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.
Sarin
S K
SK
Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India. sksarin@nda.vsnl.net.in
Sandhu
B S
BS
Sharma
B C
BC
Jain
M
M
Singh
J
J
Malhotra
V
V
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016037:Single-Blind Method; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase; D004259:DNA-Directed DNA Polymerase