BACKGROUND: The virologic impact of adding interferon to antiviral nucleoside therapy was studied in Japanese patients having perinatally transmitted hepatitis B virus (HBV) genotype C. METHODS:Sixty-four patients including 41 positive for hepatitis B e antigen (HBeAg) were assigned to receive either (1) a combination of interferon-alpha (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). RESULTS: The combination treatment enhanced the early virologic response, and HBV clearance was more frequent at week 8 for patients with baseline HBV DNA < or = 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 < or =5 log copies/ml (log-rank test, P = 0.195) were not improved. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: The virologic impact of adding interferon to antiviral nucleoside therapy was studied in Japanese patients having perinatally transmitted hepatitis B virus (HBV) genotype C. METHODS: Sixty-four patients including 41 positive for hepatitis B e antigen (HBeAg) were assigned to receive either (1) a combination of interferon-alpha (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). RESULTS: The combination treatment enhanced the early virologic response, and HBV clearance was more frequent at week 8 for patients with baseline HBV DNA < or = 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 < or =5 log copies/ml (log-rank test, P = 0.195) were not improved. CONCLUSIONS: 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.
Authors: T Aikawa; K Kanai; M Kako; T Kawasaki; K Hino; S Iwabuchi; H Tsubouchi; Y Takehira; F Tsuda; H Okamoto Journal: J Viral Hepat Date: 1995 Impact factor: 3.728
Authors: R G Knodell; K G Ishak; W C Black; T S Chen; R Craig; N Kaplowitz; T W Kiernan; J Wollman Journal: Hepatology Date: 1981 Sep-Oct Impact factor: 17.425
Authors: Neal Van Hoeven; Jessica A Belser; Kristy J Szretter; Hui Zeng; Peter Staeheli; David E Swayne; Jacqueline M Katz; Terrence M Tumpey Journal: J Virol Date: 2009-01-14 Impact factor: 5.103