中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2014年
4期
266-271
,共6页
黄明星%李新华%吴元凯%陶玲%揭育胜%李向永%时红%林国莉%杨方集
黃明星%李新華%吳元凱%陶玲%揭育勝%李嚮永%時紅%林國莉%楊方集
황명성%리신화%오원개%도령%게육성%리향영%시홍%림국리%양방집
肝炎,乙型,慢性%肝炎病毒,乙型%替诺福韦
肝炎,乙型,慢性%肝炎病毒,乙型%替諾福韋
간염,을형,만성%간염병독,을형%체낙복위
Hepatitis B,chronic%Hepatitis B virus%Tenofovir disoproxil fumarate
目的 探讨替诺福韦(TDF)在慢性乙型肝炎(CHB)经治患者中实际临床应用的疗效特点及其安全性.方法 回顾性分析TDF单独治疗30例CHB经治患者48周,比较治疗前后第4、12、24、36、48周时HBV DNA水平、HBV DNA下降水平及累积下降水平,HBV DNA不可检测率、HBV DNA阴转中位时间及观察终点时ALT复常率、HBeAg血清转换率(HBeAg-R％)、病毒学应答率(VR)、病毒学突破率(VBT)及不良事件发生率.计量资料采用t检验,计数资料采用x2检验,HBV DNA累积不可检测率采用生存分析Kaplan-Meimer方法. 结果 第4、12、24、48周的HBV DNA下降幅度分别为(2.11±0.38) logm IU/ml、(0.93±0.31) log10 IU/ml、(0.75±0.20)10g10 IU/ml、(0.16±0.19) log10 IU/ml、(0.14±0.25) log10 IU/ml,均较基线水平有明显下降(t值分别为5.582、9.303、3.123、10.759、12.202,均P＜0.01),HBV DNA水平、下降及累积下降水平在第4、12、24周差异均有统计学意义(均P＜ 0.05),而第24、36、48周各时间点差异无统计学意义(均P＞ 0.05).第4周与第24、36、48周HBV DNA不可检测率比较,差异有统计学意义(分别为P＜0.01、P=0.007、P=0.001).第48周HBV DNA累积不可检测率为96.7％.HBV DNA阴转中位时间为10.4 (3.43 ～ 34.0)周.ALT复常率从第4周的40.0％上升到第48周的100％,且第4周与第12、24、36、48周比较,差异均有统计学意义(均P＜0.05).随访终点时VR为88.9％ (8/9),HBeAg血清转换率为6.67％ (2/30),VBT为0.治疗后各时间点肌酸激酶(CK)超过正常值上限(ULN)2倍的比例平均为9.18％,CK超过2×ULN比例在治疗前后差异均无统计学意义(P=0.087).治疗后出现血清肌酐上升超过ULN比例为0. 结论 对于核苷类药物经治的CHB患者,TDF仍能早期快速抑制HBV DNA复制,且ALT复常率高,耐受性好,不良事件发生率低.
目的 探討替諾福韋(TDF)在慢性乙型肝炎(CHB)經治患者中實際臨床應用的療效特點及其安全性.方法 迴顧性分析TDF單獨治療30例CHB經治患者48週,比較治療前後第4、12、24、36、48週時HBV DNA水平、HBV DNA下降水平及纍積下降水平,HBV DNA不可檢測率、HBV DNA陰轉中位時間及觀察終點時ALT複常率、HBeAg血清轉換率(HBeAg-R％)、病毒學應答率(VR)、病毒學突破率(VBT)及不良事件髮生率.計量資料採用t檢驗,計數資料採用x2檢驗,HBV DNA纍積不可檢測率採用生存分析Kaplan-Meimer方法. 結果 第4、12、24、48週的HBV DNA下降幅度分彆為(2.11±0.38) logm IU/ml、(0.93±0.31) log10 IU/ml、(0.75±0.20)10g10 IU/ml、(0.16±0.19) log10 IU/ml、(0.14±0.25) log10 IU/ml,均較基線水平有明顯下降(t值分彆為5.582、9.303、3.123、10.759、12.202,均P＜0.01),HBV DNA水平、下降及纍積下降水平在第4、12、24週差異均有統計學意義(均P＜ 0.05),而第24、36、48週各時間點差異無統計學意義(均P＞ 0.05).第4週與第24、36、48週HBV DNA不可檢測率比較,差異有統計學意義(分彆為P＜0.01、P=0.007、P=0.001).第48週HBV DNA纍積不可檢測率為96.7％.HBV DNA陰轉中位時間為10.4 (3.43 ～ 34.0)週.ALT複常率從第4週的40.0％上升到第48週的100％,且第4週與第12、24、36、48週比較,差異均有統計學意義(均P＜0.05).隨訪終點時VR為88.9％ (8/9),HBeAg血清轉換率為6.67％ (2/30),VBT為0.治療後各時間點肌痠激酶(CK)超過正常值上限(ULN)2倍的比例平均為9.18％,CK超過2×ULN比例在治療前後差異均無統計學意義(P=0.087).治療後齣現血清肌酐上升超過ULN比例為0. 結論 對于覈苷類藥物經治的CHB患者,TDF仍能早期快速抑製HBV DNA複製,且ALT複常率高,耐受性好,不良事件髮生率低.
목적 탐토체낙복위(TDF)재만성을형간염(CHB)경치환자중실제림상응용적료효특점급기안전성.방법 회고성분석TDF단독치료30례CHB경치환자48주,비교치료전후제4、12、24、36、48주시HBV DNA수평、HBV DNA하강수평급루적하강수평,HBV DNA불가검측솔、HBV DNA음전중위시간급관찰종점시ALT복상솔、HBeAg혈청전환솔(HBeAg-R％)、병독학응답솔(VR)、병독학돌파솔(VBT)급불량사건발생솔.계량자료채용t검험,계수자료채용x2검험,HBV DNA루적불가검측솔채용생존분석Kaplan-Meimer방법. 결과 제4、12、24、48주적HBV DNA하강폭도분별위(2.11±0.38) logm IU/ml、(0.93±0.31) log10 IU/ml、(0.75±0.20)10g10 IU/ml、(0.16±0.19) log10 IU/ml、(0.14±0.25) log10 IU/ml,균교기선수평유명현하강(t치분별위5.582、9.303、3.123、10.759、12.202,균P＜0.01),HBV DNA수평、하강급루적하강수평재제4、12、24주차이균유통계학의의(균P＜ 0.05),이제24、36、48주각시간점차이무통계학의의(균P＞ 0.05).제4주여제24、36、48주HBV DNA불가검측솔비교,차이유통계학의의(분별위P＜0.01、P=0.007、P=0.001).제48주HBV DNA루적불가검측솔위96.7％.HBV DNA음전중위시간위10.4 (3.43 ～ 34.0)주.ALT복상솔종제4주적40.0％상승도제48주적100％,차제4주여제12、24、36、48주비교,차이균유통계학의의(균P＜0.05).수방종점시VR위88.9％ (8/9),HBeAg혈청전환솔위6.67％ (2/30),VBT위0.치료후각시간점기산격매(CK)초과정상치상한(ULN)2배적비례평균위9.18％,CK초과2×ULN비례재치료전후차이균무통계학의의(P=0.087).치료후출현혈청기항상승초과ULN비례위0. 결론 대우핵감류약물경치적CHB환자,TDF잉능조기쾌속억제HBV DNA복제,차ALT복상솔고,내수성호,불량사건발생솔저.
Objective To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).Methods A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated.Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline),4,12,24,36 and 48 were collected for evaluation.The lower limit of HBV DNA detection was 100 IU/ml.The serum alanine aminotransferase (ALT) normalization rate,hepatitis B e antigen (HBeAg) seroconversion rate,viral breakthrough (VBT) rate,viral response (VR) rate,and adverse events were determined upon treatment completion.Statistical analyses were carried out using the Student's t-test,the x2 test or the Kaplan-Meier method.Results Over the 48-week treatment period,HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml,t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml,t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml,t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml,t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml,t =12.202) (all P ＜ 0.01).However,the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24,36 and 48 (all P ＞ 0.05).The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml).The rate of undetectable HBV DNA at week 4 (26.7％) was significantly lower than that at weeks 24 (87.5％,P ＜ 0.01),36 (80.0％,P =0.007),and 48 (88.9％,P=0.001).The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks).At week 48,the rates ofVR,HBeAg seroconversion,and VBT were 88.9％,6.7％,and 0％ respectively.During treatment,the levels of creatine kinase were more than two times the upper limit normal in 9.2％ of the patients,and were comparable at each time point examined (all P ＞ 0.05).All patients showed a normal level of serum creatinine throughout the treatment period.Conclusion For CHB patients with non-response to NAs,TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.
