Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern
2010; Wiley; Volume: 18; Issue: 3 Linguagem: Inglês
10.1111/j.1365-2893.2010.01301.x
ISSN1365-2893
AutoresJun Inoue, Yoshiyuki Ueno, Y. Wakui, Hiroaki Niitsuma, Koji Fukushima, Y. Yamagiwa, Masaaki Shiina, Yasuteru Kondo, Eiji Kakazu, Keiichi Tamai, Noriyuki Obara, Takao Iwasaki, Tooru Shimosegawa,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoJournal of Viral HepatitisVolume 18, Issue 3 p. 206-215 Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern J. Inoue, J. Inoue Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Ueno, Y. Ueno Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Wakui, Y. Wakui Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorH. Niitsuma, H. Niitsuma Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorK. Fukushima, K. Fukushima Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Yamagiwa, Y. Yamagiwa Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorM. Shiina, M. Shiina Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Kondo, Y. Kondo Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorE. Kakazu, E. Kakazu Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorK. Tamai, K. Tamai Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorN. Obara, N. Obara Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorT. Iwasaki, T. Iwasaki Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorT. Shimosegawa, T. Shimosegawa Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this author J. Inoue, J. Inoue Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Ueno, Y. Ueno Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Wakui, Y. Wakui Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorH. Niitsuma, H. Niitsuma Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorK. Fukushima, K. Fukushima Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Yamagiwa, Y. Yamagiwa Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorM. Shiina, M. Shiina Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorY. Kondo, Y. Kondo Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorE. Kakazu, E. Kakazu Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorK. Tamai, K. Tamai Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorN. Obara, N. Obara Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorT. Iwasaki, T. Iwasaki Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this authorT. Shimosegawa, T. Shimosegawa Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, JapanSearch for more papers by this author First published: 08 February 2011 https://doi.org/10.1111/j.1365-2893.2010.01301.xCitations: 39 Yoshiyuki Ueno, Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba-ku, Sendai 980-8574, Japan. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Summary. To investigate the efficacy of long-term lamivudine (3TC) and adefovir dipivoxil (ADV) combination therapy in 3TC-resistant chronic hepatitis B virus (HBV) infected patients, we analysed 28 3TC-resistant patients treated with the combination therapy during 47 months (range, 9–75). At 12, 24, 36, and 48 months, the rates of virological response with undetectable HBV DNA (≤2.6 log copies/mL) were 56, 80, 86, and 92%, respectively. Among 17 hepatitis B e antigen (HBeAg)-positive patients, HBeAg disappeared in 24% at 12 months, 25% at 24 months, 62% at 36 months, and 88% at 48 months. When HBV genotypes were compared, patients with genotype B achieved virological response significantly more rapidly than those with genotype C (P = 0.0496). One patient developed virological breakthrough after 54 months, and sequence analysis of HBV obtained from the patient was performed. An rtA200V mutation was present in the majority of HBV clones, in addition to the 3TC-resistant mutations of rtL180M+M204V. The rtN236T ADV-resistant mutation was observed in only 25% clones. In vitro analysis showed that the rtA200V mutation recovered the impaired replication capacity of the clone with the rtL180M+M204V mutations and induced resistance to ADV. Moreover, rtT184S and rtS202C, which are known entecavir-resistant mutations, emerged in some rtL180M+M204V clones without rtA200V or rtN236T. In conclusion, 3TC+ADV combination therapy was effective for most 3TC-resistant patients, especially with genotype B HBV, but the risk of emergence of multiple drug-resistant strains with long-term therapy should be considered. The mutation rtA200V with rtL180M+M204V may be sufficient for failure of 3TC+ADV therapy. Citing Literature Supporting Information Table S1 Clonal analysis of HBV RT region of samples from the patient with lamivudine and adefovir resistance. Filename Description JVH_1301_sm_TableS1.doc45 KB Supporting info item Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume18, Issue3March 2011Pages 206-215 RelatedInformation
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