血清HBV RNA在HBeAg阴性慢性乙型肝炎患者中的检测价值

Value of serum HBV RNA in HBeAg-negative patients with chronic hepatitis B

目的分析经恩替卡韦治疗后血清HBVDNA已降至"检测值下限"的慢性乙型肝炎患者中血清HBVRNA的水平,并探究HBVRNA水平与患者肝脏生物化学指标之间的相关性。以期为新型血清学标志物HBVRNA的临床意义奠定研究基础。方法纳入接受规范的核苷类药物抗病毒治疗12个月以上,HBeAg发生阴转,且连续6个月血清HBVDNA检测结果均为低于检测下限的慢性乙型肝炎患者107例。采用PerkinElmer公司的研发试剂检测血清中HBVRNA水平,采用罗氏Cobas检测血清中HBVDNA水平,使用HITACHI全自动生物化学分析仪检测丙氨酸氨基转移酶、天冬氨酸氨基转移酶,使用ARCHITECT化学发光分析仪检测HBsAg、HBeAg、抗-HBe、抗-HBc。用RStudio软件对HBVRNA水平与患者肝脏生物化学指标之间的相关性进行分析;采用Logistic回归分析影响HBVRNA水平的独立影响因素。结果经恩替卡韦治疗后血清HBVDNA已降至低于检测下限的慢性乙型肝炎患者中血清HBVRNA的阳性检出率为22.43%。HBVRNA阳性组患者中HBsAg、丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平略高于HBVRNA阴性组;抗-HBc在HBVRNA阴性组中水平略高。抗-HBe在HBVRNA阴性组和阳性组中水平差异无统计学意义。经Logistic回归分析结果显示抗-HBc是影响HBVRNA检测水平的独立影响因素(P=0.021)。结论经恩替卡韦治疗后血清HBVDNA已降至低于检测下限的慢性乙型肝炎患者中仍有部分患者可检出HBVRNA,而血清HBVRNA仅来源于cccDNA的直接转录,故比HBVDNA和HBsAg更能反映cccDNA水平或者活性。抗-HBc作为影响HBVRNA水平的独立影响因素,有可能联合使用作为预测抗病毒疗效的新指标。

Objective To analyze serum HBV-RNA levels in patients with chronic hepatitis B whose serum HBV-DNA has dropped to undetected levels after treatment with entecavir, and to explore the correlation between HBV-RNA level and liver biochemical parameters, which lay the research foundation for the clinical significance of new serological marker HBV-RNA. Methods HBeAg negatively detected 107 cases with chronic hepatitis B whose serum HBV-DNA test results were lower than detection level for six consecutive months after receiving standard nucleoside therapy for more than 12 months were included. HBV-RNA level was detected by Perkin-Elmer reagent. HBV-DNA level was detected by Roche Cobas. Hitachi automatic biochemical analyzer was used to detect ALT and AST. Architect chemiluminescence analyzer was used to detect HBsAg, HBeAg, anti-HBe and anti-HBc. RStudio software was performed to analyze the correlation between HBV-RNA level and liver biochemical parameters. Logistic regression was used to analyze the independent factors influencing HBV-RNA level. Results The positive detection rate of serum HBV-RNA in patients with chronic hepatitis B whose serum HBV-DNA had dropped to undetected levels after ETV treatment was 22.43%. HBsAg, ALT and AST levels in HBV-RNA positive group were slightly higher than HBV-RNA negative group, while anti-HBc levels were slightly higher in HBV-RNA negative group. There was no difference in the level of anti-HBe between the HBV-RNA negative and the positive group. Logistic regression analysis showed that anti-HBc was an independent factor influencing the level of HBV-RNA detection (P = 0.021). Conclusion HBV-RNA can be detected in some patients with chronic hepatitis B whose serum HBV-DNA level has dropped to undetected levels after ETV treatment. Serum HBV-RNA only comes from the direct transcription of cccDNA, so it is better than HBV-DNA and HBsAg to reflect cccDNA level or activity. Anti-HBc, as an independent factor influencing the level of HBV-RNA, may be used in combination as a new marker to predict the efficacy of antiviral therapy.