302 100039 5 R975. 5 A 1003-3734 2013 11-1269 - 06 Recent advances of the treatment of chronic hepatitis B with tenofovir ZHANG Ning LUO Sheng-qiang 302 Hospital of PLA Beijing 100039 China Abstract Tenofovir TDF is the fifth nucleoside nucleotide analogue drug approved in Europe and USA to inhibit the replication of HBV. In this article we reviewed the recent advances in pharmacological action pharmacokinetics and clinical research for the treatment of chronic hepatitis B with TDF and mentioned the clinical practice suggestion of the use of TDF. Key words tenofovir chronic hepatitis B hepatitis B virus lamivudine TDF LAM adefovir ADV entecavir ETV telbivudine LDT emtricitabine FTC 2008 TDF HBV TDF CHB 5 CHB HBV 2009 TDF CHB 1 HBV TDF C 19 H 30 N 5 O 10 P C 4 H 4 O 4 2001 635. 52 tenofovir disoproxil fumarate TDF HIV HIV /HBV HBV HBV 张宁, 女, 主治医师联系电话 : ( 010 ) 66933129-6036,E-mail: zhangning198191@ sina. com. cn 罗生强, 男, 主任医师, 主要从事肝病的临床及科研工 作联系电话 : ( 010) 66933436,E-mail: w302528@ sohu. com 1 1269
TDF 300 mg d -1 n =45 TDF 300 mg d -1 /FTC 200 mg d -1 2 HBV n = 45 ETV 0. 5 1 mg d - 1 n = 22 48 HBV /HIV CHB HBV 2 mg dl - 1 < 2 mg dl - 1 TDF 1 3 1. 2 2. 2 Ⅲ TDV-102 103 7 15 106 HBeAg HBeAg 641 2 1 ~ 2 h 18 ~ 69 Knodell 3 HBsAg 6 102 HBeAg 40% ALT 1 ~10 ULN HBV DNA 10 5 copies ml -1 10 h 1 12 CYP LAM FTC 12 4 103 70% ~ HBeAg ALT 2 ~ 80% 10 ULN HBV DNA 10 6 copies ml - 1 TDF 12 5 2 1 2 TDF 300 mg d - 1 ADV 10 mg d - 1 2. 1 II Liaw 6 5 48 HBV DNA HBV DNA < 400 39 TDF copies ml - 1 69 IU ml - 1 112 CHB Knodell 2 HBV DNA 10 3 copies ml - 1 Child-Pugh 7 ~ 12 ADV TDV ALT 10 ULN 50 ml min - 1 7. 5 g dl - 1 WBC 1. 5 10 9 L - 1 PLT 3 10 9 L - 1 AFP 20 ng ml - 1 3 TDF 6 6 1. 1 HBV DNA 5'- HBV < 400 HIV-1 HIV-2 HBV copies ml - 1 69 IU ml - 1 70. 5% 87. 8% TDF 72. 7% 56. 8% 75. 6% 54. 5% HBeAg / 21% /21% 27% / 5'- 13% 0% /0% 3 CHILD-PUGH CTP DNA DNA ETV TDF HBV DNA 3'-OH DNA ETV HBeAg ETV HBV DNA HBeAg HBsAg ADV P < 0. 05 1 1270
1 HBeAg n = 176 HBeAg n = 90 n = 250 HBeAg n = 125 HBV DNA /% 66 a 12 71 a 49 /% 74 68 72 69 Knodell 4. 7 ± 1. 82 a 5. 2 ± 1. 96 4. 4 ± 1. 82 4. 4 ± 1. 81 HBV DNA /% 76 a 13 93 a 63 /% 68 a 54 76 77 HBeAg /% 21 18 HBsAg /% 3. 2 a 0 a TDV ADV P < 0. 05 2. 3 LAM HBeAg Tan 8 13 HBV DNA 5. 97 log 10 copies ml - 1 ADV 58% LAM LAM ADV TDF 5 13 10 48 81% 13 ADV HBV DNA < 400 copies ml - 1 9 LAM ADV LAM 8 LAM TDF FTC ADV ADV 1 LAM 1 ADV 4 Patterson 10 LAM ADV TDV ADV ADV TDF 18 8 ~ 52 8 60 48. 5 21 ~ 80 3 46 77% 40 67% HBeAg rta181v rtn236t 5 38 63% ADV TDF 3 rta181v rti233v 24 rtn236t 10 TDF LAM TDF LAM 8 1 ADV ADV TDF LAM TDF ADV 20 33% LAM 17 FTC 1 28% ADV HBV ADV TDF DNA 5. 33 log 10 IU ml - 1 ADV 3 TDV FTC 3 ~ 12 1 d 10 2 ADV HBV DNA TDF ADV 12 24 48 96-2. 86 3. 23 3. 75 4. 03 ADV log 10 IU ml - 1 48 27 46% HBV HBV DNA HBV DNA < 15 IU ml - 1 DNA < 15 IU ml - 1 96 38 64% Berg 9 4 28 HBV DNA < 15 IU ml - 1 HBV DNA ADV TDF TDF 24 ~ 96 HBV DNA > 1 000 copies ml - 1 LAM ADV 105 TDF 300 mg d - 1 Petersen 11 TDF /FTC 300 /200 mg d - 1 57 1271
CHB TDF ETV 3 HBV DNA TDF ETV HBeAg CHB 57 TDF HBeAg CHB 45 37 HBeAg 24 HBeAg HBV DNA 1. 5 10 4 IU ml - 1 TDF HBV DNA 88% 21 51 6 TDF 66% HBeAg HBV DNA 20% HBsAg 5% HBV DNA ADV ETV 53% 3 56% 5 HBeAg 1HBV DNA 61% 2 15 18 20 21 27 1 HBsAg 70% HBsAg 1% 2 3 HBeAg TDF HBV DNA HCC 1 73% 2 HBV DNA Pan 12 ETV CHB HBeAg 264 24 1 log 10 TDF HBeAg 115 ETV 0. 5 mg d - 1 14 71% C 29% B 41. 5 19 ~ 64 9 12 1 LAM 1 HBV DNA < 50 IU ml - 1 83. 2% 76. 4% 85. 7% HBeAg HBeAg HBV DNA 108 HBV DNA 7. 55 5. 30 ~ 9. 40 log 10 IU ml - 1 HBV DNA copies ml - 1 57% 4 80. 4% ETV 69. 8% C TDF HBeAg ETV 64. 5 ETV 26 ~ 126 TDF HBV DNA 3. 69 3. 00 ~ 4. 90 log 10 copies ml - 1 TDF 30 HBV DNA ALT HBeAg 12 2 HBeAg 75 3 16 84 TDF 50 24 ~ 160 144 TDF 72% HBeAg TDF 87% HBeAg HBV DNA Sarrecchia 13 TDF 400 copies ml - 1 ADV ETV TDF 71% HBeAg 88% 2. 4 74% HBeAg 81% HBeAg Woo 14 meta TDV CHB HBV DNA 8% HBeAg LAM ADV ETV HBsAg 5 LDT TDF 3 17 2009 10 31 TDF HBeAg CHB 20 ALT AST 12 HBV DNA CHB HBeAg HBeAg HBeAg 1272 HBsAg 94% 1 65% Lok 15 379 ETV 0. 5 mg d - 1 TDF 300 mg d - 1 100 96 HBV DNA HBV DNA HBeAg ETV TDF 2. 5 TDF TDF Ⅲ HBeAg HBV DNA 400 copies ml -1 CHB
TDF 300 mg qd po TDF 1 TDF 4 18 2 TDF TDF ADV 65 5% 13% 10% 9% 8% 7% 7% 7% 6% 3 TDF TDF 3 5% TDF FDA TDF B TDF 14 19 5 TDF HBV DNA 4 TDF TDF CHB TDF < 50 ml min - 1 30 ~ 49 ml min - 1 TDF 300 mg 48 h 1 10 ~29 ml min -1 TDF 300 mg 72 ~ 96 h 1 TDF 300 mg 7 d 1 12 h 1 < 10 ml min - 1 HBeAg HBV 2 18 - TDF 19 1 BHATTACHARYA D THIO CL. Review of hepatitis B thera- 5 CHB TDF peutics J 2 GISH R JIA JD LOCARNINI S 6 LdT Dis 2012 12 4 341-353. LdT 3 DECHRISTOFORO R PENZAK SR. Tenofovir a nucleotide analogue reverse-transcriptase inhibitor for treatment of HIV in- fection J. Am J Health Syst Pharm 2004 61 1 4 BUTI M LdT 7 TDF 5 LOK AS Hepatology 2009 50 3 661-662. 6 LIAW YF SHEEN IS LEE CM et al. Tenofovir disoproxil fumarate TDF emtricitabine /TDF and entecavir in patients with decompensated chronic hepatitis B liver disease J. Hepa- TDF ADV TDF ADV tology 2011 TDF 102 103 48 HBeAg. Clin Infect Dis 2010 1 10 1201-1208. et al. Selection of chronic hepatitis B therapy with high barrier to resistance J. Lancet Infect 86-98. HOMS M. Tenofovir disoproxil fumarate in the treatment of chronic hepatitis B J. Expert Rev Gastroenterol Hepatol 2012 6 4 413-421. MCMAHON BJ. Chronic hepatitis B update 2009 J. 53 1 62-72. 1310 1273
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