Asf. Lok et al., PREDICTIVE VALUE OF PRECORE HEPATITIS-B VIRUS MUTATIONS IN SPONTANEOUS AND INTERFERON-INDUCED HEPATITIS-B E-ANTIGEN CLEARANCE, Hepatology, 21(1), 1995, pp. 19-24
We previously reported two mutually exclusive mutations in the precore
region of hepatitis B virus: M1 (T-1856, proline-serine substitution
at codon 15) and M2 (A-1896, stop codon at codon 28). This study was c
onducted to determine if the presence of precore mutants affect sponta
neous or interferon (IFN)-induced hepatitis B e antigen (HBeAg) cleara
nce. Sera from 201 hepatitis B e antigen positive Chinese patients (in
cluding 106 who participated in a controlled trial of IFN therapy) wit
h chronic hepatitis B virus (HBV) infection were analyzed by direct se
quencing of HBV DNA after amplification by polymerase chain reaction (
PCR) assay. Forty-three (21%) patients had M1 (T-1856), and 20 patient
s (10%) had M2 (A-1896). During a follow-up period of 1 to 7 years, 75
%, 28%, and 26% of those with M2 (A-1896), M1 (T-1856), and wild type
sequence respectively, cleared HBeAg (P < .0001). Eighteen (67%) of 27
patients with wild-type sequence but none of 10 patients who had M1 (
T-1856) in their initial samples developed M2 (A-1896) after loss of H
BeAg (P < .0001). Sustained antiviral response was achieved in 55%, 0%
, and 17% of interferon-treated patients who had M2 (A-1896), M1 (T-18
56), and wild-type sequence, respectively, initially (P = .04). Howeve
r, patients with M2 (A-1896) were also more likely to have elevated pr
etreatment aminotransferase levels (P = .02). In summary, HBeAg-positi
ve Chinese patients with M2 (A-1896) were more likely to clear HBeAg,
and to do so earlier. Nevertheless, development or selection of M2 (A-
1898) was not a prereqpisite for HBeAg clearance. Interferon therapy d
id not increase the rate of HBeAg clearance in patients with M2 (A-189
6) when stratified for aminotransferase levels.