高敏HBV DNA及HBsAg定量对低病毒载量慢性乙型肝炎的临床价值

The clinical significance of high-sensitive HBV DNA and HBsAg quantitative detection for chronic hepatitis B patients with low viral load

目的了解慢性乙型肝炎(chronic hepatitis B,CHB)患者的高敏HBV DNA载量、HBsAg定量、丙氨酸氨基转移酶(alanine aminotransferase,ALT)等观察指标在慢性HBV感染者中的临床价值。方法回顾分析2019年1月至2019年11月在解放军联勤保障部队第910医院肝病中心就诊的654例CHB患者的临床检测和病例资料,分析指标主要包括高敏HBV DNA、HBsAg、HBeAg、ALT、高尔基体蛋白73(Golgi protein 73,GP73)。结果654例CHB患者中,539例(82.41%)HBV DNA<2000 IU/mL,427例(65.29%)HBV DNA<500 IU/mL。ALT、GP73异常率、HBeAg阳性率及HBsAg含量在不同HBV DNA载量患者间差异均有统计学意义(均P<0.05),且HBsAg含量在<20 IU/mL、20~499 IU/mL与500~2000 IU/mL间两两相比均存在显著差异(均P<0.01)。阳性高敏HBV DNA病毒量与ALT、GP73、HBsAg含量间均存在显著意义的曲线相关性(均P<0.01),相关系数分别为0.394、0.369、0.415。在HBeAg(-)患者中,HBV DNA 20~499 IU/mL组别的ALT异常率显著高于<20 IU/mL组(P=0.048);HBeAg(+)患者中,ALT、GP73异常率在两组间差异均无统计学意义(P=0.366、0.120)。427例HBV DNA<500 IU/mL CHB患者HBV DNA阳性率、ALT异常率与抗病毒治疗时间均呈负相关(P<0.01);GP73异常率、HBeAg阳性率与治疗时间无相关性(P=0.165、0.367)。未治疗组ALT异常率与治疗时间为1~2年、2~3年、大于3年相比均差异有统计学意义(P=0.023、0.009、0.001);未治疗组ALT异常患者中的HBV DNA阳性率与治疗时间为2~3年、>3年组间差异均有统计学意义(P=0.028、0.010)。结论高敏HBV DNA检测结合HBsAg定量能够更加准确了解病毒复制情况,对于HBV DNA<500 IU/mL抗病毒治疗患者,动态监测高敏HBV DNA,能显著降低病毒持续低水平复制引起的患者肝损伤,对临床治疗及预后有重要意义。

Objective To investigate the clinical significance of high-sensitive detection of HBV DNA,in combination with quantitative detection of hepatitis B surface antigen(HBsAg)and serum level of alanine aminotransferase(ALT)for chronic hepatitis B(CHB)viral infected patients.Methods Six hundred and fifty-four CHB patients were retrospectively analyzed for their clinical data and parameters including highly sensitive HBV DNA,HBsAg,hepatitis B e antigen(HBeAg),ALT,and Golgi protein 73(GP73).The patients were divided into HBV DNA load<20,20~499,500~2000,and>2000 IU/mL groups based on a highly sensitive HBV DNA detection by real-time quantitative fluresence polymerase chain reaction.Results Among the 654 CHB patients,82.41%had HBV DNA<2000 IU/mL and 65.29%had HBV DNA<500 IU/mL.Abnormal rates of ALT and GP73,positive rate of HBeAg and HBsAg were significantly different among the four groups(All P<0.05).HBsAg content was significantly different between the groups of<20 IU/mL,20~499 IU/mL and 500~2000 IU/mL(all P<0.001).There was a significant curve correlation(P<0.001)between positive and highly sensitive HBV DNA viral load and ALT,GP73 and HBsAg levels,and the correlation coefficients R were 0.394,0.369 and 0.415,respectively.In HBeAg(-)patients,the abnormal rate of ALT in the HBV DNA 20~499 IU/mL group was significantly higher than that in the<20 IU/mL group(P=0.048).In HBeAg(+)patients,the abnormal rates of ALT and GP73 were not significantly different between these two groups(P=0.366,0.120).The HBV DNA positive rate,ALT abnormal rate and antiviral treatment duration of 427 patients with HBV DNA<500 IU/mL were significantly negatively correlated(P=0.001,<0.001).There was no significant trend correlation between the abnormal GP73 rate and the positive HBeAg rate and the treatment time(P=0.165,0.367).The abnormal rate of ALT in the untreated group was significantly different from that of the treatment duration of 1 to 2 years,2 to 3 years,and more than 3 years(P=0.023,0.009,0.001).There were statistically significant differences between the HBV DNA positive rate and the treatment duration of 2 to 3 years and>3 years in patients with abnormal ALT in the untreated group(P=0.028,0.010).Conclusion The combination of high-sensitivity HBV DNA detection with HBsAg quantification is more accurate in reflecting the viral replication status.For patients with HBV DNA<500 IU/mL under antiviral therapy,dynamic and high-sensitive monitoring of HBV DNA may help in controling liver damage caused by persistent low-level of viral replication,which is of great significance for guiding clinical treatment and prognosis.