TDF 300 mg d -1 n =45 TDF 300 mg d -1 /FTC 200 mg d -1 2 HBV n = 45 ETV mg d - 1 n = HBV /HIV CHB HBV 2 mg dl - 1 < 2 mg dl - 1 TDF 1 3 1

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1 R A Recent advances of the treatment of chronic hepatitis B with tenofovir ZHANG Ning LUO Sheng-qiang 302 Hospital of PLA Beijing 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 tenofovir disoproxil fumarate TDF HIV HIV /HBV HBV HBV 张宁, 女, 主治医师联系电话 : ( 010 ) , 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) , w302528@ sohu. com

2 TDF 300 mg d -1 n =45 TDF 300 mg d -1 /FTC 200 mg d -1 2 HBV n = 45 ETV mg d - 1 n = HBV /HIV CHB HBV 2 mg dl - 1 < 2 mg dl - 1 TDF Ⅲ TDV HBeAg HBeAg ~ 2 h 18 ~ 69 Knodell 3 HBsAg HBeAg 40% ALT 1 ~10 ULN HBV DNA 10 5 copies ml h 1 12 CYP LAM FTC % ~ HBeAg ALT 2 ~ 80% 10 ULN HBV DNA 10 6 copies ml - 1 TDF TDF 300 mg d - 1 ADV 10 mg d II Liaw HBV DNA HBV DNA < TDF copies ml IU ml CHB Knodell 2 HBV DNA 10 3 copies ml - 1 Child-Pugh 7 ~ 12 ADV TDV ALT 10 ULN 50 ml min g dl - 1 WBC L - 1 PLT L - 1 AFP 20 ng ml TDF HBV DNA 5'- HBV < 400 HIV-1 HIV-2 HBV copies ml IU ml % 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 <

3 1 HBeAg n = 176 HBeAg n = 90 n = 250 HBeAg n = 125 HBV DNA /% 66 a a 49 /% Knodell 4. 7 ± a 5. 2 ± ± ± HBV DNA /% 76 a a 63 /% 68 a HBeAg /% HBsAg /% 3. 2 a 0 a TDV ADV P < LAM HBeAg Tan 8 13 HBV DNA log 10 copies ml - 1 ADV 58% LAM LAM ADV TDF % 13 ADV HBV DNA < 400 copies ml LAM ADV LAM 8 LAM TDF FTC ADV ADV 1 LAM 1 ADV 4 Patterson 10 LAM ADV TDV ADV ADV TDF 18 8 ~ ~ % 40 67% HBeAg rta181v rtn236t % 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 log 10 IU ml - 1 ADV 3 TDV FTC 3 ~ 12 1 d 10 2 ADV HBV DNA TDF ADV ADV log 10 IU ml % HBV HBV DNA HBV DNA < 15 IU ml - 1 DNA < 15 IU ml % Berg HBV DNA < 15 IU ml - 1 HBV DNA ADV TDF TDF 24 ~ 96 HBV DNA > copies ml - 1 LAM ADV 105 TDF 300 mg d - 1 Petersen 11 TDF /FTC 300 /200 mg d

4 CHB TDF ETV 3 HBV DNA TDF ETV HBeAg CHB 57 TDF HBeAg CHB HBeAg 24 HBeAg HBV DNA IU ml - 1 TDF HBV DNA 88% TDF 66% HBeAg HBV DNA 20% HBsAg 5% HBV DNA ADV ETV 53% 3 56% 5 HBeAg 1HBV DNA 61% HBsAg 70% HBsAg 1% 2 3 HBeAg TDF HBV DNA HCC 1 73% 2 HBV DNA Pan 12 ETV CHB HBeAg log 10 TDF HBeAg 115 ETV 0. 5 mg d % C 29% B ~ LAM 1 HBV DNA < 50 IU ml % 76. 4% 85. 7% HBeAg HBeAg HBV DNA 108 HBV DNA ~ log 10 IU ml - 1 HBV DNA copies ml % % ETV 69. 8% C TDF HBeAg ETV ETV 26 ~ 126 TDF HBV DNA ~ log 10 copies ml - 1 TDF 30 HBV DNA ALT HBeAg 12 2 HBeAg TDF ~ TDF 72% HBeAg TDF 87% HBeAg HBV DNA Sarrecchia 13 TDF 400 copies ml - 1 ADV ETV TDF 71% HBeAg 88% % HBeAg 81% HBeAg Woo 14 meta TDV CHB HBV DNA 8% HBeAg LAM ADV ETV HBsAg 5 LDT TDF TDF HBeAg CHB 20 ALT AST 12 HBV DNA CHB HBeAg HBeAg HBeAg 1272 HBsAg 94% 1 65% Lok ETV 0. 5 mg d - 1 TDF 300 mg d HBV DNA HBV DNA HBeAg ETV TDF 2. 5 TDF TDF Ⅲ HBeAg HBV DNA 400 copies ml -1 CHB

5 TDF 300 mg qd po TDF 1 TDF TDF TDF ADV 65 5% 13% 10% 9% 8% 7% 7% 7% 6% 3 TDF TDF 3 5% TDF FDA TDF B TDF TDF HBV DNA 4 TDF TDF CHB TDF < 50 ml min ~ 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 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 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 BUTI M LdT 7 TDF 5 LOK AS Hepatology 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 HBeAg. Clin Infect Dis et al. Selection of chronic hepatitis B therapy with high barrier to resistance J. Lancet Infect HOMS M. Tenofovir disoproxil fumarate in the treatment of chronic hepatitis B J. Expert Rev Gastroenterol Hepatol MCMAHON BJ. Chronic hepatitis B update 2009 J

6 1 MAEMONDO M INOUE A KOBAYSSHI K et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR J. N Engl J Med MITSUDOMI T MORITA S YATABE Y et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor WJTOG3405 an open label randomised phase 3 trial J. Lancet Oncol ZHOU C WU YL CHEN G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer OPTIMAL CTONG a multicentre open-label randomised phase 3 study J. Lancet Oncol EGFR-TKI J. CSCO SUM Y ShI YK ZhANG L et al. Overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial J. J Clin Oncol Suppl 15 S J FUKUOKA M YANO S GIACCONE G et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer The IDEAL 1 Trial corrected J. J Clin Oncol JACKMAN DM HOLMES AJ LINDEMAN N et al. Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib J. J Clin Oncol LUO DX HUANG MJ ZHANG XX et al. Salvage treatment with erlotinib after gefitinib failure in advanced non-small-cell lung cancer patients with poor performance status a matched-pair case-control study J. Thoracic Cancer COSTA DB NGUYEN KS CHO BC et al. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib J. Clin Cancer Res LEE DH KIM SW SUN C et al. Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment J. Ann Oncol CHO BC IM CK PARK MS et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib J. J Clin Oncol / 檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾檾 MARCELLIN P HEATHCOTE EJ BUTI M et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B J. N Engl J Med TAN J DEGERTEKIN B WONG SN et al. Tenofovir monotherapy is effective treatment failure Toadefovir in the absence of adefovir-resistant mutations J. J Hepatol BERG T MARCELLIN P ZOULIM F et al. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection J. Gastroenterology PATTERSON SJ GEORGE J STRASSER SI et al. Tenofovir disoproxil fumarate Rescue therapy following failure of both lamivudine and adefovirdipivoxil in chronic hepatitis B J. Gut PETERSEN J RATZIU V BUTI M et al. Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients an international multicenter cohort study J. J Hepatol PAN CQ HU KQ YU AS et al. Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir J. J Viral Hepat SARRECCHIA C SVICHER V VOLPI A et al. Successful switch to tenofovir after suboptimal response to entecavir in an immunocompromised patient with chronic hepatitis B and without genotypic hepatitis B virus resistance J. Infection WOO G TOMLINSON G NISHIKAWA Y et al. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B a systematic review and bayesian meta-analyses J. Gastroenterology LOK AS TRINH H CAROSI G et al. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos t ide-na ve patients with chronic hepatitis B J. Gastroenterology HEATHCOTE EJ MARCELLIN P BUTI M et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B J. Gastroenterology European Association for The Study of The Liver. EASL Clinical Practice Guidelines Management of chronic hepatitis B virus infection J. J Hepatol BUSTER EH BAAK BC BAKKER CM et al. The 2012 revised Dutch national guidelines for the treatment of hronic hepatitis B irus infection J. Neth J Med DF J /

一试验目的背景及已知对人体的可能危险与受益 1. 试验目的 : 观察并比较高危 IB-IIIA 期非小细胞肺癌根治术后 EGFR 突变型患者接受化疗或化疗 + 埃克替尼维持治疗的疗

一试验目的背景及已知对人体的可能危险与受益 1. 试验目的 : 观察并比较高危 IB-IIIA 期非小细胞肺癌根治术后 EGFR 突变型患者接受化疗或化疗 + 埃克替尼维持治疗的疗版本号 :1.0 日期 :2011.01.20 化疗 + 埃克替尼维持治疗对 EGFR 突变型非小细胞肺癌根治术后患者生存获益的影响主要研究者 : 蔡开灿研究单位 : 南方医科大学南方医院胸心血管外科保密声明 : 本研究方案中所包含的信息仅提供给