不同HBV DNA检测方法对PEG-IFNɑ-2b治疗HBeAg阳性慢性乙型肝炎疗效判断的影响

Impact of HBV DNA detection methods on evaluating the clinical effect of PEG-IFNɑ-2b in treatment of HBeAg-positive chronic hepatitis B: a comparative analysis

目的在PEG-IFNα-2b治疗HBeAg阳性慢性乙型肝炎(CHB)过程中,探讨应用不同HBV DNA检测方法对疗效判断的影响。方法选取2014年9月-2016年1月天津市第二人民医院收治的CHB患者,应用PEG-IFNα-2b治疗24周内,HBV DNA低敏方法检测(最低检测下限500 IU/ml)首次阴转,且36周内低敏检测持续阴性的HBeAg阳性CHB患者83例。36周内采用高敏方法检测(最低检测下限20 IU/ml)持续阴性的患者(阴性组)33例,持续阳性的患者(阳性组)50例。对比2组在12、24和36周时HBeAg、HBsAg下降水平以及HBeAg血清学转换率。正态分布的计量资料2组间比较采用成组t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验,计数资料2组间比较采用χ~2检验。结果在HBV DNA低敏检测阴性后的12、24和36周,阴性组HBeAg下降值均明显优于阳性组,差异均有统计学意义[0.32(0.16~0.92)log_(10)COI vs 0.14(0.01~0.30)log_(10)COI,Z=-3.061,P=0.002;0.44(0.19~1.15)log_(10)COI vs 0.16(0.04~0.35)log_(10)COI,Z=-3.043,P=0.002;0.51(0.36~1.21)log_(10)COI vs 0.24(0.10~0.46)log_(10)COI,Z=-3.880,P<0.001]。在HBV DNA低敏检测阴性后的12周,2组HBsAg下降水平差异无统计学意义(P=0.067),但在24和36周阴性组HBsAg下降值均明显高于阳性组,差异均有统计学意义[0.13(-0.02~0.33)log_(10)IU/ml vs 0.08(-0.02~0.16)log_(10)IU/ml,Z=-2.207,P=0.021;0.16(0.03~0.47)log_(10)IU/ml vs 0.03(-0.08~0.20)log_(10)IU/ml,Z=-2.363,P=0.018]。在HBV DNA低敏检测阴性后12周,阴性组HBeAg血清学转换率为30.30%,阳性组为16.00%,2组比较差异无统计学意义(P=0.174),24和36周阴性组HBeAg血清学转换率分别为36.36%和39.39%,明显高于阳性组的16.00%和18.00%,2组比较差异均有统计学意义(χ~2=4.507,P=0.040;χ~2=4.671,P=0.042)。结论在PEG-IFN治疗HBeAg阳性CHB的过程中,为更准确的判断患者的抗病毒疗效,HBV DNA应该采用高度敏感的方法检测。

Objective To investigate the impact of different HBV DNA detection methods on evaluating the clinical effect of PEG - IFNα - 2b in the treatment of HBeAg - positive chronic hepatitis B （CHB）. Methods A total of 83 CHB patients who were admitted to Tianjin Second People＇s Hospital from September 2014 to January 2016 and treated with PEG - IFNα -2b for less than 24 weeks with clearance for the first time detected by HBV DNA low - sensitivity method （ the lower limit of detection was 500 IU/ml） and negative results within 36 weeks obtained by low- sensitivity detection. Among these patients, 33 patients with negative results within 36 weeks obtained by high - sensitivity detection （the lower limit of detection was 20 IU/ml） were enrolled in negative group, and 50 with positive results were enrolled in positive group. The reductions in HBeAg and HBsAg and HBeAg seroconversion rate at 12, 24, and 36 weeks were compared between the two groups. The independent - samples t test was used for comparison of normally distributed continuous data between groups, the Mann - Whitney U rank sum test was used for comparison of non - normally distributed continuous data between groups, and the chi - square test was used for comparison of categorical data between groups. Results At 12, 24, and 36 weeks after negative results were obtained by HBV DNA low - sensitivity detection, the negative group had a significant reduction in HBeAg than the positive group [ 12 weeks ： 0.32 （0.16 - 0.92） log10 COl vs 0. 14 （0.01 -0.30） log10 COI, Z = -3. 061, P =0. 002; 24 weeks： 0.44 （0.19 - 1.15） logw COI vs 0.16 （0.04 -0.35） lOgl0 COI, Z = - 3. 043, P = 0. 002 ; 36 weeks ： 0.51 （0.36 - 1.21 ） lOglo COI vs 0.24 （0.10 - 0.46） loglo COI, Z = - 3. 880, P 〈 0. 001 ]. At 12 weeks after negative results were obtained by HBV DNA low- sensitivity deteetion, there was no significant difference in the reduction in HBsAg （ P = 0. 067 ）, while at 24 and 36 weeks, the negative group had a signifieant reduction in HBsAg than the positive group [24 weeks： 0.13 （ -0.02 -0.33） lOglo IU/ml vs 0.08 （ -0.02 -0.16） log10 IU/ml, Z = -2. 207, P =0. 021 ; 36 weeks： 0.16 （0.03 -0. 47） log10 IU/ml vs 0.03 （ -0.08 -0.20） log10 IU/ml, Z = -2. 363, P =0. 018]. At 12 weeks after negative results were obtained by HBV DNA low -sensitivity deteetion, there was no significant difference in the HBeAg seroconversion rate between the negative group and the positive group （30.30% vs 16.00% , P =0. 174） , while at 24 and 36 weeks, there were significant differences between the two groups （36.36% vs 16.00% and39.39% vs 18.00% ,X^2 =4.507 and4.671, P=0.040 and0.042）. Conclusion Inthe treatment of HBeAg - positive CHB using PEG - IFN, high - sensitivity detection methods should be used to aeeurately evaluate the effeet of antiviral therapy.