Initial Virological Response and Viral Mutation with Adefovir Dipivoxil Added to Ongoing Lamivudine Therapy in Lamivudine-Resistant Chronic Hepatitis B
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Shuang Wu Kenichi Fukai Fumio Imazeki Makoto Arai Tatsuo Kanda Yutaka Yonemitsu Osamu Yokosuka
- چاپ و سال / کشور: 2010
Description
Background Although adefovir dipivoxil (ADV) has been used for antiviral treatment of lamivudine (LAM)- resistant chronic hepatitis B (CHB) patients, the long-term efficacy of this treatment is not well understood. Initial virological response (IVR) has been reported to be an important factor in relation to the development of ADV-resistance. Aims We therefore examined the factors associated with IVR and ADV mutation in these patients. Methods Forty-nine LAM-resistant CHB patients with ADV add-on LAM therapy, 47% of whom were hepatitis B e-antigen (HBeAg)-positive with median treatment duration of 23 months, were enrolled in this study. Patients were classified into IVR and non-IVR groups on the basis of viral suppression status. Mutational analysis of the HBV polymerase/reverse transcriptase (rt) domain was performed by PCR-direct sequencing. Results Serum HBV DNA was undetectable (\2.6 log10 copies/mL) in 67, 82, and 84% of patients at 24, 48, and 96 weeks, respectively, after ADV add-on LAM therapy. IVR was achieved in 82% of patients, and ALT normalized at week 24 in 90% of IVR and 78% of non-IVR patients. The lower pretreatment HBV DNA level and virus-containing mutations other than double mutation of rtL180M ? rtM204V were significantly associated with IVR (P = 0.002 and P = 0.014, respectively). ADVresistant mutations in the RT motif, reported previously, were not detected. Conclusion IVR is useful for predicting the antiviral efficacy of ADV and LAM combination therapy in LAMresistant CHB.
Dig Dis Sci (2011) 56:1207–1214 DOI 10.1007/s10620-010-1423-y Received: 16 June 2010 / Accepted: 3 September 2010 / Published online: 7 October 2010
