82 Chinese Journal of Practical Internal Medicine Jan. 2013 Vol. 33 No. 1 Keywords hepatitis B chronic drug resistance nucleoside and nucleotide analogs management 1005-2194 2013 01-0082 - 10 R512. 6 + 2 A NAs 1 NAs HCC 4 LAM ADV LdT ETV TDF NAs genetic barrier NAs 1-4 2008 LAM 1 24% 5 70% 7-9 LdT 2 HBeAg 5 2009 6 25% 11% 10-11 ADV 5 HBeAg 42% 29% 12-13 ADV HBeAg 5 14. 6% 14 Infection International electronic edition 1. 7% 1. 2% 15-16 TDF 2 Ⅲ ETV 3 426 176 HBeAg 250 HBeAg TDF 144 34 8% HBV DNA 400 /ml 69 IU /ml 10 32 ~ 120 100191 zhuangbmu@ 126. com 200040 wengxinhua@ fudan. edu. cn TDF 20 72 ~ 96 4 HBV DNA 400 /ml 69 IU /ml 17 NAs
2013 1 33 1 83 NAs NAs 3 12 NAs 80% ~ 90% HBV DNA 1 lg IU /ml 4-5 81% NAs 2. 8 partial virological response 30% LAM 35% ADV 6 24 110 741 684 HBV DNA 1 lg IU /ml 4 LAM 39. 6% 18 NAs NAsLAM LdT 6 24 NAsETV NAs TDF 12 48 2 2. 9 complete virological re- PCR 19-20 ung 21 sponse LAM HCC 78% 0. 22 2. 10 biochemical response ALT 2 ULN ALT 2 HCC 2. 11 virological breakthrough 9 22-25 HBV DNA 2 2. 12 biochemical breakthrough 2. 1 primary drug resistance mutation ALT ALT ULN 27 2. 13 virological rebound 26 2. 2 secondary drug resistance mutation compensatory drug resistance mutation 5 ULN 3 ALT ALT 29 26 3 2. 3 genotypic resistance HBV 3. 1 26 2. 4 phenotypic resistance 26 HBV 1 1 HBV 10 12 ~ 10 13 EC 50 HCV 26 HIV 10 100 HBV 2. 5 cross resistance 1 1 HBV 1. 4 ~ 3. 2 10-5 30 HBV 2. 6 multidrug resistance 2 HBV DNA 3 1 lg IU /ml 1 2 5 25 NAs 2. 7 primary non-response quasispecies NAs ALT 2 ULN HBV DNA 28 2. 14 hepatitis flare ALT
84 Chinese Journal of Practical Internal Medicine Jan. 2013 Vol. 33 No. 1 NAs L HBV RT LAM LdT D ETV ADV TDF 3 5 NAs 25-26 1 1 2 31 32 3. 2 40% 27 Chotiyaputta 41 2007 2008 2009 26 32 3. 2. 1 1 HBV DNA 95% 31 33-35 39. 7% 46. 1% HBV 47% ~ 49% 1 LdT 19% ~ 24% 16 GLOBE HBV DNA HBV DNA < 9 lg /ml HBeAg HBV DNA < 7 lg /ml HBeAg 2 3. 2. 3 36 HBV HBV 32 37-38 1 HBV 10-5 2 3 39-40 NAs 10-10 10-15 LAM LdT ADV 3. 2. 2 1 ETV 23-25 1 LAM ADV ETV TDF 3 31 3
2013 1 33 1 85 42-44 TDF ADV 44-45 HIV HBV TDF rtl180m rta194t rtm204v 46 HCC LAM 1 42 - ETV 43 LAM ETV 5 5 51% 47 5 5 32 5. 1 L rt204 ADV rtm204v /I L LAM LdT D LAM LdT 42-43 ETV 57 5. 2 rt236 rtn236t ADV TDF TDF 43 ADV TDF 5. 3 rt181 L ADV TDF 40% ADV 23 4-5% LAM 5 4 HBV ADV TDF ORF 44 NAs 5. 5 ETV rtl180m + rtm204v /I + HBV rti169 rtt184 rt202 rtm250 1 HBsAg HBsAg 3 ETV 19 NAs 48-51 1 HBV rta181t rtm204i 1 HBV sw172 * sw196 * 1 HBV LAM LdT ETV ADV TDF rta181t /sw172 * M204V M204I L180M + M204V R R R R R I I I A181T /V I /R R R I N236T R I 52 - V173L ± M250V HCC 56 L180M + M204V /I ± T184G ± 202I /G rta181t /sw172 * 5. 4 rta181t /V + rtn236t L LAM LdT L180M + M204V /I ± I169T ± I R R R R R R R
86 Chinese Journal of Practical Internal Medicine Jan. 2013 Vol. 33 No. 1 6 NAs NAs NAs 26 NAs Villet 43 1 LAM LAM ADV LAM ADV rtv173l + L180M + A181V + N236T LAM ADV LAM ADV 26 PCR HBV DNA 58 7 NAs 1 NAs 1 PCR 61 90% PCR 20% 4 20 28 59 NAs 20% 2 PCR 62 PCR 10 ~ 30 60 PCR 8 8. 1 HBV DNA HBV DNA 3 RFLP 26 5% PCR HBV DNA IU /ml 4 1 IU /ml 5 ~ 6 /ml INNO-LiPA 63-66 5% NAs HBV 26 62-63 DNA 9 3 1 HBV DNA 3 ~ 6 1 4 9. 1 8. 2 9. 1. 1 NAs LAM LAM 4 4 HBV RT
2013 1 33 1 87 ETV NAs ADV NAs ETV TDF ADV LAM LdT ETV LAM LdT 9. 2 ADV TDF 26 31 HBV DNA 1 HBV DNA 9. 1. 2 NAs 2 4-5 NAs LAM LdT 24 Peg IFN 70 ADV TDF ADV 48 LdT Peg IFN 71 2 1 NAs HBV DNA LAM LdT ADV ETV 24 HBV DNA 2 ~ 4 Keeffe 67 NAs 24 HBV DNA TDF EFFORT NIH NCT00962533 76 74. 0% 61. 1% P = 0. 001 NAs 1. 4% 11. 4% P < 0. 001 68 ETV TDF 48 NAs ETV HBV DNA TDF 48 HBV DNA HBV DNA > 2 10 10 IU /L HBV DNA 5 20 10 69 ETV ADV TDF TDF 2 LAM LdT ETV TDF TDF ADV ADV ETV TDF + LAMLdT LAM TDF ETV LAM LdT LAM LAM LdT ADV
88 Chinese Journal of Practical Internal Medicine Jan. 2013 Vol. 33 No. 1 10. 1 1998 LAM 200 10. 4 NAs NAs NAs NAs NAs LAM ADV LAM ETV 10. 2 LAM ADV 3 NAs ADV 26 74 10. 5 3 NAs ETV TDF ALT HBeAg 5-6 72 NAs 10. 6 NAs 70. 7% NAs 73 NAs ETV TDF 10. 7 NAs 2 4 74-76 10. 3 Hongthanakorn 60 40% 22% ~ 27% 46. 3% 77 LAM 78 16 LAM LdT ADV LAM NAs NAs
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