中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2014年
2期
100-106
,共7页
李国军%喻一奇%范平%邵凌云%陈少隆%洪捷敏%修自力%林琪%李昌水
李國軍%喻一奇%範平%邵凌雲%陳少隆%洪捷敏%脩自力%林琪%李昌水
리국군%유일기%범평%소릉운%진소륭%홍첩민%수자력%림기%리창수
HBeAg阳性慢性乙型肝炎%HBsAg定量%聚乙二醇干扰素α-2a%核苷(酸)类似物
HBeAg暘性慢性乙型肝炎%HBsAg定量%聚乙二醇榦擾素α-2a%覈苷(痠)類似物
HBeAg양성만성을형간염%HBsAg정량%취을이순간우소α-2a%핵감(산)유사물
HBeAg-positive chronic hepatitis B%Quantification of HBsAg%Peginterferon α 2a%Nucleos(t)ide analogue
目的 观察长期核苷(酸)类似物(NUC)治疗未达到慢性乙型肝炎防治指南(2010年)停药标准的HBeAg阳性CHB患者加用聚乙二醇干扰素(peg-INF)-α-2a联合治疗的疗效,并探讨HBeAg/HBsAg消失的预测因素.方法 回顾性分析83例接受NUC治疗≥1年未实现病毒学或血清学应答的HBeAg阳性CHB患者,加用(peg-INF)-α-2a联合治疗48周,记录治疗12周和24周时HBV血清学标志物等指标值,停药后随访24周.以加用peg-INF的时间点定义为基线,探讨基线HBsAg水平和治疗过程中HBsAg下降程度对HBeAg/HBsAg消失的预测价值.受试者工作特征(ROC)曲线用于确定基线HBsAg水平对联合治疗后HBsAg消失的预测价值,Cox回归模型用于分析与联合治疗后HBeAg/HBsAg消失相关的因素;计算每个变量的风险比(HR),并纳入单因素和多因素分析.结果 peg-INF-α-2a停药24周后,50例患者HBeAg消失,占60.2％;27例HBeAg血清学转换,占32.5％;23例HBsAg消失,占27.7％;12例HBsAg血清学转换,占14.5％.基线HBsAg＜1 000 IU/mL的11例患者均HBeAg消失,与基线HBsAg 1 000～3 000 IU/mL(共12例,8例HBeAg消失;HR=0.215,95％CI:0.078～0.591; P=0.003)和＞3 000 IU/mL(共60例,31例HBeAg消失;HR=0.251,95％CI:0.120～0.526;P=0.000)的患者比较,更易实现HBeAg消失.结论 对于长期NUC治疗未取得病毒学或血清学应答的患者,加用peg INF-α-2a时的血清HBsAg水平对HBeAg和HBsAg消失具有预测价值.基线HBsAg＜1 000 IU/mL者,联合治疗后可获得高HBeAg和HBsAg阴转率;而HBsAg＞1 000 IU/mL(包括HBsAg＞3 000 IU/mL)者,联合治疗12周时的HBsAg较基线下降水平可预测HBeAg/HBsAg的阴转.
目的 觀察長期覈苷(痠)類似物(NUC)治療未達到慢性乙型肝炎防治指南(2010年)停藥標準的HBeAg暘性CHB患者加用聚乙二醇榦擾素(peg-INF)-α-2a聯閤治療的療效,併探討HBeAg/HBsAg消失的預測因素.方法 迴顧性分析83例接受NUC治療≥1年未實現病毒學或血清學應答的HBeAg暘性CHB患者,加用(peg-INF)-α-2a聯閤治療48週,記錄治療12週和24週時HBV血清學標誌物等指標值,停藥後隨訪24週.以加用peg-INF的時間點定義為基線,探討基線HBsAg水平和治療過程中HBsAg下降程度對HBeAg/HBsAg消失的預測價值.受試者工作特徵(ROC)麯線用于確定基線HBsAg水平對聯閤治療後HBsAg消失的預測價值,Cox迴歸模型用于分析與聯閤治療後HBeAg/HBsAg消失相關的因素;計算每箇變量的風險比(HR),併納入單因素和多因素分析.結果 peg-INF-α-2a停藥24週後,50例患者HBeAg消失,佔60.2％;27例HBeAg血清學轉換,佔32.5％;23例HBsAg消失,佔27.7％;12例HBsAg血清學轉換,佔14.5％.基線HBsAg＜1 000 IU/mL的11例患者均HBeAg消失,與基線HBsAg 1 000～3 000 IU/mL(共12例,8例HBeAg消失;HR=0.215,95％CI:0.078～0.591; P=0.003)和＞3 000 IU/mL(共60例,31例HBeAg消失;HR=0.251,95％CI:0.120～0.526;P=0.000)的患者比較,更易實現HBeAg消失.結論 對于長期NUC治療未取得病毒學或血清學應答的患者,加用peg INF-α-2a時的血清HBsAg水平對HBeAg和HBsAg消失具有預測價值.基線HBsAg＜1 000 IU/mL者,聯閤治療後可穫得高HBeAg和HBsAg陰轉率;而HBsAg＞1 000 IU/mL(包括HBsAg＞3 000 IU/mL)者,聯閤治療12週時的HBsAg較基線下降水平可預測HBeAg/HBsAg的陰轉.
목적 관찰장기핵감(산)유사물(NUC)치료미체도만성을형간염방치지남(2010년)정약표준적HBeAg양성CHB환자가용취을이순간우소(peg-INF)-α-2a연합치료적료효,병탐토HBeAg/HBsAg소실적예측인소.방법 회고성분석83례접수NUC치료≥1년미실현병독학혹혈청학응답적HBeAg양성CHB환자,가용(peg-INF)-α-2a연합치료48주,기록치료12주화24주시HBV혈청학표지물등지표치,정약후수방24주.이가용peg-INF적시간점정의위기선,탐토기선HBsAg수평화치료과정중HBsAg하강정도대HBeAg/HBsAg소실적예측개치.수시자공작특정(ROC)곡선용우학정기선HBsAg수평대연합치료후HBsAg소실적예측개치,Cox회귀모형용우분석여연합치료후HBeAg/HBsAg소실상관적인소;계산매개변량적풍험비(HR),병납입단인소화다인소분석.결과 peg-INF-α-2a정약24주후,50례환자HBeAg소실,점60.2％;27례HBeAg혈청학전환,점32.5％;23례HBsAg소실,점27.7％;12례HBsAg혈청학전환,점14.5％.기선HBsAg＜1 000 IU/mL적11례환자균HBeAg소실,여기선HBsAg 1 000～3 000 IU/mL(공12례,8례HBeAg소실;HR=0.215,95％CI:0.078～0.591; P=0.003)화＞3 000 IU/mL(공60례,31례HBeAg소실;HR=0.251,95％CI:0.120～0.526;P=0.000)적환자비교,경역실현HBeAg소실.결론 대우장기NUC치료미취득병독학혹혈청학응답적환자,가용peg INF-α-2a시적혈청HBsAg수평대HBeAg화HBsAg소실구유예측개치.기선HBsAg＜1 000 IU/mL자,연합치료후가획득고HBeAg화HBsAg음전솔;이HBsAg＞1 000 IU/mL(포괄HBsAg＞3 000 IU/mL)자,연합치료12주시적HBsAg교기선하강수평가예측HBeAg/HBsAg적음전.
Objective To investigate the efficacy of add-on peginterferon α-2a in patients with hepatitis B e antigen (HBeAg)-positive hepatitis who failed to achieve virological or serological response to long-term treatment of nucleos(t)ide analogues and to explore the predictive value of hepatitis B surface antigen (HBsAg) quantification on the HBeAg and HBsAg loss.Methods Eighty-three HBeAg-positive chronic hepatitis B (CHB) patients who failed to achieve virological or serological response after more than one-year nucleos(t) ide analogues treatment were added with peginterferon α-2a for 48 weeks and were further followed up for 24 weeks after treatment.HBsAg was quantified at baseline and throughout the antiviral therapy (week 12 and 24) and its predictive value on the HBeAg and HBsAg loss was explored.Receiver operating characteristics (ROC) curve was used to identify the predictive value of baseline HBsAg level on HBsAg loss.Cox regression model was used to analyze the factors associated with HBeAg and HBsAg loss.Multivariable-adjusted hazard ratios (HR) were derived for each factor using univariate and multivariate analysis.Results Twenty-four weeks after drug withdrawal,50(60.2％) patients achieved HBeAg loss,27 (32.5％) achieved HBeAg seroconversion,23 (27.7％) achieved HBsAg loss while 12 (14.5％) achieved HBsAg seroconversion.In patients with an HBsAg level of ＜ 1 000 IU/mL,11 (100.0％) patients achieved HBeAg loss.Compared to patients with an HBsAg level of ＜1 000 IU/mL,the rates of HBeAg loss were lower in those with HBsAg level of 1 000-3 000 IU/mL (8/12,66.7％) and ＞3 000 IU/mL (31/60,51.7％),with hazard ratios (HR) of 0.215 (95％CI:0.078-0.591) and 0.251 (95％ CI:0.120-0.526),respectively.As to HBsAg loss,10 patients (90.9％) achieved HBsAg loss with an HBsAg level of ＜1 000 IU/mL,compared with only 8 patients (13.3％) achieved HBsAg loss with an HBsAg level of ＞3 000 IU/mL.An HBsAg level of ＞ 3 000 IU/mL was found to be associated with a lower possibility of HBsAg loss (HR=0.155,95％CI:0.055-0.439; P=0.000).Conclusions Baseline HBsAg level predicts HBeAg and HBsAg loss in patients treated with add-on peginterferon after a long-term treatment of nucleos (t)ide analogues.The efficacy is better in patients with a baseline HBsAg level of ＜1 000 IU/mL.Patients with a baseline HBsAg level of ＞1 000 IU/mL (including those with a baseline HBsAg level of ＞3 000 IU/mL) who achieve a significant HBsAg decline at week 12 during treatment still have a chance to achieve HBeAg or HBsAg loss,while those with mild HBsAg decline should be advised to discontinue the combination therapy.
