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We conduct this meta\u2010analysis to appraise the pooled incidence of spontaneous hepatitis\n B<\/jats:styled-content>\n virus resistance mutations worldwide and its distribution.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We searched\n P<\/jats:styled-content>\n ub\n M<\/jats:styled-content>\n ed,\n EMBASE<\/jats:styled-content>\n ,\n C<\/jats:styled-content>\n hinese\n B<\/jats:styled-content>\n iomedical\n L<\/jats:styled-content>\n iterature\n D<\/jats:styled-content>\n atabase, and\n C<\/jats:styled-content>\n hina\n N<\/jats:styled-content>\n ational\n K<\/jats:styled-content>\n nowledge\n I<\/jats:styled-content>\n nfrastructure until\n D<\/jats:styled-content>\n ecember 31, 2013. Cross\u2010sectional or case\u2010control studies reporting incidence of natural resistance mutations in untreated\n CHB<\/jats:styled-content>\n patients were included. Pooled incidence was performed in fixed\u2010 or random\u2010effects models, and heterogeneity among studies was assessed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 106 studies were included involving 12\u2009212 naive\n CHB<\/jats:styled-content>\n patients. The summarized incidence of natural mutations worldwide was 5.73% (95% confidence interval [\n CI<\/jats:styled-content>\n ]: 4.85\u20136.61%), primary mutation rate 5.39% (95%\n CI<\/jats:styled-content>\n : 4.54\u20136.24%), and secondary mutation rate 2.94% (95%\n CI<\/jats:styled-content>\n : 1.59\u20134.29%). The pooled incidence reached up to 8.00% (95%\n CI<\/jats:styled-content>\n : 6.63\u20139.38%) in\n C<\/jats:styled-content>\n hina, higher than that in other countries (1.88% [95%\n CI<\/jats:styled-content>\n : 1.06\u20132.69%]). Mutation rt\n M<\/jats:styled-content>\n 204\n V<\/jats:styled-content>\n \/\n I<\/jats:styled-content>\n had the highest incidence of 4.89% (95%\n CI<\/jats:styled-content>\n : 4.13\u20135.65%), and other primary mutations seldom spontaneously occurred. In subgroup analysis, genotype\n C<\/jats:styled-content>\n hepatitis\n B<\/jats:styled-content>\n virus infection, male, and hepatitis\n B<\/jats:styled-content>\n antigen (\n HB<\/jats:styled-content>\n e\n A<\/jats:styled-content>\n g) negative patients had a slightly higher natural mutation rate.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The resistance mutations occurred frequently in untreated\n CHB<\/jats:styled-content>\n patients, especially in\n C<\/jats:styled-content>\n hina. The lamivudine resistance had the highest natural prevalence rate, while other nucleos(t)ide analogues showed rarely spontaneous resistance. Detecting the spontaneous resistance mutations will benefit the clinical management of\n CHB<\/jats:styled-content>\n patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jgh.12831","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T04:24:56Z","timestamp":1413433496000},"page":"252-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Incidence of natural resistance mutations in na\u00efve chronic hepatitis\n B<\/scp>\n patients: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"30","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"An","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(14)60220\u20108"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8211155"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22962"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-012-9365-4"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23190"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2010.01274.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.01.001"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21698"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-008-9048-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.063"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1619"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.12.005"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)00023-4"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00145-9"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04567.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2007.00877.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04151.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(89)90455-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i6.867"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21189"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24078"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.6712"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035052"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1177\/135965350901400206","article-title":"Association of baseline viral factors with response to lamivudine therapy in chronic hepatitis B patients with high serum alanine aminotransferase levels","volume":"14","author":"Tseng TC","year":"2009","journal-title":"Antivir. 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