TITLE

Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection

AUTHOR(S)
Yuki, Nobukazu; Nagaoka, Takayuki; Nukui, Kazuhiko; Omura, Masao; Hikiji, Kazumasa; Kato, Michio
PUB. DATE
June 2008
SOURCE
Journal of Gastroenterology;2008, Vol. 43 Issue 6, p457
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The virologic impact of adding interferon to antiviral nucleoside therapy was studied in Japanese patients having perinatally transmitted hepatitis B virus (HBV) genotype C. Sixty-four patients including 41 positive for hepatitis B e antigen (HBeAg) were assigned to receive either (1) a combination of interferon-α (6 million units daily for 2 weeks, then three times weekly) plus lamivudine (100 mg daily) for 24 weeks followed by lamivudine alone for 28 weeks ( n = 30) or (2) 52-week lamivudine monotherapy ( n = 34). The combination treatment enhanced the early virologic response, and HBV clearance was more frequent at week 8 for patients with baseline HBV DNA ≤ 7 log copies/ml (90% vs. 33%, P = 0.013) and at week 24 for patients with baseline HBV DNA > 7 log copies/ml (75% vs. 40%, P = 0.080). In the combination arm, YMDD mutants emerged less often at week 52 (8% vs. 30%, P = 0.047). However, reversion of the precore mutation was more prominent with combination treatment than with monotherapy (McNemar test, P = 0.014 and P = 0.103, respectively). HBeAg seroconversion ( P = 0.429) and sustained off-treatment HBV suppression to ≤5 log copies/ml (log-rank test, P = 0.195) were not improved. Simultaneous commencement of treatment with interferon and a nucleoside analog may be worthy as a treatment option to augment the early virologic response and prevent drug resistance in difficult-to-treat patients. Combination treatment was also shown to enhance reversion of the precore mutation. Further studies are warranted to clarify the therapeutic implications of this phenomenon.
ACCESSION #
32960080

 

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