caa a22 4500 445795921 CHVBK 20180317145125.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10620-010-1423-y doi (NATIONALLICENCE)springer-10.1007/s10620-010-1423-y Initial Virological Response and Viral Mutation with Adefovir Dipivoxil Added to Ongoing Lamivudine Therapy in Lamivudine-Resistant Chronic Hepatitis B [Elektronische Daten] [Shuang Wu, Kenichi Fukai, Fumio Imazeki, Makoto Arai, Tatsuo Kanda, Yutaka Yonemitsu, Osamu Yokosuka] 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 23months, 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 96weeks, 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). ADV-resistant 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 LAM-resistant CHB. Springer Science+Business Media, LLC, 2010 Chronic hepatitis B nationallicence Adefovir dipivoxil nationallicence Lamivudine nationallicence Initial virological response nationallicence Mutation nationallicence ADV : Adefovir dipivoxil nationallicence ALT : Alanine aminotransferase nationallicence CHB : Chronic hepatitis B nationallicence HBV : Hepatitis B virus nationallicence IVR : Initial virological response nationallicence LAM : Lamivudine nationallicence rt : Reverse transcriptase nationallicence Wu Shuang Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Fukai Kenichi Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Imazeki Fumio Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Arai Makoto Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Kanda Tatsuo Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Yonemitsu Yutaka Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Yokosuka Osamu Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/4(2011-04-01), 1207-1214 0163-2116 56:4<1207 2011 56 10620 https://doi.org/10.1007/s10620-010-1423-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1423-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wu Shuang Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Fukai Kenichi Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Imazeki Fumio Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Arai Makoto Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Kanda Tatsuo Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Yonemitsu Yutaka Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 700 1- Yokosuka Osamu Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, 260-8670, Chiba City, Chiba, Japan aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/4(2011-04-01), 1207-1214 0163-2116 56:4<1207 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer