肝脏
肝髒
간장
CHINESE HEPATOLOGY
2014年
6期
395-398
,共4页
谢敬东%陈榕%刘芸野%蔡伟%王晖%郭清%谷瑞瑛%周霞秋%谢青
謝敬東%陳榕%劉蕓野%蔡偉%王暉%郭清%穀瑞瑛%週霞鞦%謝青
사경동%진용%류예야%채위%왕휘%곽청%곡서영%주하추%사청
慢性乙型肝炎%恩替卡韦%长期治疗%病毒学抑制
慢性乙型肝炎%恩替卡韋%長期治療%病毒學抑製
만성을형간염%은체잡위%장기치료%병독학억제
Chronic hepatitis B%Entecavir%Long-term therapy%Viral suppression
目的:了解恩替卡韦单药治疗至少5年对核苷(酸)类药物初治的 HBeAg 阳性慢性乙型肝炎患者的疗效和安全性。方法选择BMS463-012和BMS463-023研究项目在瑞金医院感染科入组的20例 HBeAg 阳性慢性乙型肝炎核苷初治患者。所有患者在第一阶段(第1~2年)口服恩替卡韦0.5 mg/d,第二阶段(第3~5年)口服恩替卡韦1.0 mg/d。检测并记录基线以及治疗48、96、144、192和240周时患者的ALT、HBV DNA、HBeAg和 HBsAg水平。如治疗240周时HBV DNA ≥300拷贝/mL,则进行基因序列测定以明确是否发生耐药。结果恩替卡韦治疗第48、96、144、192和240周,HBV DNA <300拷贝/mL的比例分别为60%、40%、50%、85%和85%,HBeAg消失率分别为15%、15%、20%、30%和65%。有3例患者在第192周发生 HBeAg 血清学转换。恩替卡韦治疗48周时血清 HBV DNA<300拷贝/mL 与>300拷贝/mL患者相比,240周病毒学应答率分别为100%和66.7%;240周 HBeAg 血清学转换率分别为27.3%和0。入组患者中基线ALT>2倍和<2倍患者相比,前者240周病毒学应答率为100%,后者为75%;前者240周 HBeAg 血清学转换率为37.5%,而后者为0。入组患者基线高病毒载量(>108拷贝/mL)和低病毒载量(<108拷贝/mL)比较,前者240周病毒学应答率为83.3%,后者为100%;前者240周 HBeAg血清学转换率为11.1%,而后者为50%。以上二者相比,均差异有统计学意义(P<0.05)。基线、治疗48、96、144、192和240周血清 HBsAg 水平分别为(4.04±0.40)、(3.64±0.44)、(3.73±0.41)、(3.53±0.55)、(3.55±0.55)和(3.55±0.63)lg IU/mL。相对于基线,在第48周、144周、192周、240周 HBsAg效价有明显下降(P值分别为0.005、0.005、0.009、0.018)。治疗240周时 HBeAg消失和未消失的患者,其基线 HBsAg效价(3.95±0.54)lg IU/mL比(4.20±0.48)lg IU/mL,差异有统计学意义(P=0.005)。在长达5年的恩替卡韦治疗过程中未出现任何严重不良事件。结论 HBeAg阳性慢性乙型肝炎核苷类初治患者接受恩替卡韦单药长期治疗能获得持久的病毒学抑制,5年未发生耐药。
目的:瞭解恩替卡韋單藥治療至少5年對覈苷(痠)類藥物初治的 HBeAg 暘性慢性乙型肝炎患者的療效和安全性。方法選擇BMS463-012和BMS463-023研究項目在瑞金醫院感染科入組的20例 HBeAg 暘性慢性乙型肝炎覈苷初治患者。所有患者在第一階段(第1~2年)口服恩替卡韋0.5 mg/d,第二階段(第3~5年)口服恩替卡韋1.0 mg/d。檢測併記錄基線以及治療48、96、144、192和240週時患者的ALT、HBV DNA、HBeAg和 HBsAg水平。如治療240週時HBV DNA ≥300拷貝/mL,則進行基因序列測定以明確是否髮生耐藥。結果恩替卡韋治療第48、96、144、192和240週,HBV DNA <300拷貝/mL的比例分彆為60%、40%、50%、85%和85%,HBeAg消失率分彆為15%、15%、20%、30%和65%。有3例患者在第192週髮生 HBeAg 血清學轉換。恩替卡韋治療48週時血清 HBV DNA<300拷貝/mL 與>300拷貝/mL患者相比,240週病毒學應答率分彆為100%和66.7%;240週 HBeAg 血清學轉換率分彆為27.3%和0。入組患者中基線ALT>2倍和<2倍患者相比,前者240週病毒學應答率為100%,後者為75%;前者240週 HBeAg 血清學轉換率為37.5%,而後者為0。入組患者基線高病毒載量(>108拷貝/mL)和低病毒載量(<108拷貝/mL)比較,前者240週病毒學應答率為83.3%,後者為100%;前者240週 HBeAg血清學轉換率為11.1%,而後者為50%。以上二者相比,均差異有統計學意義(P<0.05)。基線、治療48、96、144、192和240週血清 HBsAg 水平分彆為(4.04±0.40)、(3.64±0.44)、(3.73±0.41)、(3.53±0.55)、(3.55±0.55)和(3.55±0.63)lg IU/mL。相對于基線,在第48週、144週、192週、240週 HBsAg效價有明顯下降(P值分彆為0.005、0.005、0.009、0.018)。治療240週時 HBeAg消失和未消失的患者,其基線 HBsAg效價(3.95±0.54)lg IU/mL比(4.20±0.48)lg IU/mL,差異有統計學意義(P=0.005)。在長達5年的恩替卡韋治療過程中未齣現任何嚴重不良事件。結論 HBeAg暘性慢性乙型肝炎覈苷類初治患者接受恩替卡韋單藥長期治療能穫得持久的病毒學抑製,5年未髮生耐藥。
목적:료해은체잡위단약치료지소5년대핵감(산)류약물초치적 HBeAg 양성만성을형간염환자적료효화안전성。방법선택BMS463-012화BMS463-023연구항목재서금의원감염과입조적20례 HBeAg 양성만성을형간염핵감초치환자。소유환자재제일계단(제1~2년)구복은체잡위0.5 mg/d,제이계단(제3~5년)구복은체잡위1.0 mg/d。검측병기록기선이급치료48、96、144、192화240주시환자적ALT、HBV DNA、HBeAg화 HBsAg수평。여치료240주시HBV DNA ≥300고패/mL,칙진행기인서렬측정이명학시부발생내약。결과은체잡위치료제48、96、144、192화240주,HBV DNA <300고패/mL적비례분별위60%、40%、50%、85%화85%,HBeAg소실솔분별위15%、15%、20%、30%화65%。유3례환자재제192주발생 HBeAg 혈청학전환。은체잡위치료48주시혈청 HBV DNA<300고패/mL 여>300고패/mL환자상비,240주병독학응답솔분별위100%화66.7%;240주 HBeAg 혈청학전환솔분별위27.3%화0。입조환자중기선ALT>2배화<2배환자상비,전자240주병독학응답솔위100%,후자위75%;전자240주 HBeAg 혈청학전환솔위37.5%,이후자위0。입조환자기선고병독재량(>108고패/mL)화저병독재량(<108고패/mL)비교,전자240주병독학응답솔위83.3%,후자위100%;전자240주 HBeAg혈청학전환솔위11.1%,이후자위50%。이상이자상비,균차이유통계학의의(P<0.05)。기선、치료48、96、144、192화240주혈청 HBsAg 수평분별위(4.04±0.40)、(3.64±0.44)、(3.73±0.41)、(3.53±0.55)、(3.55±0.55)화(3.55±0.63)lg IU/mL。상대우기선,재제48주、144주、192주、240주 HBsAg효개유명현하강(P치분별위0.005、0.005、0.009、0.018)。치료240주시 HBeAg소실화미소실적환자,기기선 HBsAg효개(3.95±0.54)lg IU/mL비(4.20±0.48)lg IU/mL,차이유통계학의의(P=0.005)。재장체5년적은체잡위치료과정중미출현임하엄중불량사건。결론 HBeAg양성만성을형간염핵감류초치환자접수은체잡위단약장기치료능획득지구적병독학억제,5년미발생내약。
Objective Durable hepatitis B virus (HBV)DNA suppression is important to antiviral effectiveness in chronic hepatitis B (CHB). In this study,we analyzed the long-term efficacy and resistance profile of entecavir (ETV) monotherapy in 20 Chinese patients with nucleoside nave CHB treated for at least 5 years. Methods Twenty HBeAg positive patients with HBV DNA level 107 copies/mL and alanine aminotransferase (ALT)level 2-fold upper limit of normal (ULN)received ETV 0.5 or 1 mg/day for accumulated 5 years. Serum HBV DNA level,HBeAg status and HBsAg level were assessed at baseline and at year 1 ,2 ,3 ,4 and 5 . Gene sequencing was also conducted in the patients whose serum HBV DNA level > 300 copies/mL at year 5 . Results The ratio of HBV DNA undetectable (<300 copies/mL)for these 20 patients were 60% ,40% ,50% ,85% and 85% at year 1,2,3,4 and 5 respectively. The ratios of HBeAg loss were 15% ,15% ,20% ,30% and 65% at year 1,2,3,4 and 5,respectively. Three of 20 patients (15% )achieved HBeAgseroconversion at year 4 and 5 . Variables were compared between the patients whose serum HBV DNA < 300 copies/mL and those of patients > 300 copies/mL at week 48. Virological response rate was 100% and 66.7% at week 240 in the former's and the latter's,respectively;HBeAg seroconversion rate was 27.3% and 0 at week 240 in the former's and latter's, respectively. Virological response rate was 100% at week 240 in the patients whose ALT level 2-fold ULN,and was only 75% in the patients whose ALT level < 2-fold ULN;Meanwhile,the rate of HBeAg seroconversion was 37.5% and 0 in the former's and latter's. The rate of HBeAg seroconversion was 1 1 .1% at week 240 in the patients whose HBV DNA level>108 copies/mL at baseline,and was only 50% in the patients whose HBV DNA level <108 copies/mL at baseline,the statistics had significant difference (P<0.05). The mean serum HBsAg levels of the patients were (4.04±0.40)log10 IU/mL,(3.64±0.44)log10 IU/mL,(3.73±0.41)log10 IU/mL,(3.53±0.55)log10 IU/mL,(3.55±0.55)log10 IU/mL and (3.55±0.63)log10 IU/mL at baseline and at year 1,2,3,4 and 5,respectively. HBsAg levels had a greater mean reduction at year 1 (P= 0.005),3 (P= 0.005),4 (P= 0.009)and 5 (P= 0.018)compared with baseline, respectively. The HBsAg titers at baseline were significantly different between the patients whose HBeAg loss (3.95 ± 0.54)log10 IU/mL and HBeAg non-loss (4.20±0.48)log10 IU/mL at week 240 (P= 0.005). Non adverse effect was observed in this study. Conclusion These analysis demonstrates that long-term treatment of ETV monotherapy is effective in maintaining viral suppression. No ETV resistance substitution are detected in these patients.