干扰素对慢性乙型肝炎患者肝细胞内HBV cccDNA、血清HBsAg、HBV-DNA的影响研究

Study on influence of interferon on changes of HBV cccDNA in hepatocytes and serum HBsAg and HBV-DNA of patients with chronic hepatitis B

目的探讨干扰素α治疗慢性乙型病毒性肝炎肝细胞内HBV cccDNA、血清内HBV-DNA、HBsAg、丙氨酸氨基转移酶(ALT)的改变以及改变之间的联系。方法随机选取适合干扰素治疗慢性乙型肝炎患者31例,给予干扰素α治疗48周,检测治疗前、后肝细胞内HBV cccDNA、血清HBV-DNA、HBsAg、ALT,采用IBM SPSS Statistics(Version 20)软件进行分析。结果所有肝组织标本均检测出HBV cccDNA;肝细胞内HBV cccDNA下降(2.52±1.60)log cps/cell、HBV-DNA下降(1.51±1.02)log IU/ml、ALT下降(100.8±63.1)U/L、HBsAg下降(1.18±0.85)log ng/ml;基线水平肝细胞内HBV cccDNA同HBV-DNA有相关性:log(HBV-DNA/ml)=3.55+0.44×log(HBV cccDNA/cell),R2=0.197,P<0.01;干扰素α治疗48周后肝细胞内HBV cccDNA同血液HBsAg载量相关性:log(HBsAg/ml)=4.23+0.78×log(HBV cccDNA/cell),R2=0.616,P<0.01。结论定量PCR方法可以成功检测出肝组织内HBV cccDNA;干扰素α治疗慢性乙型病毒性肝炎48周能够减少肝组织内HBV cccDNA,降低血清病毒载量、稳定肝功能;血清HBsAg在干扰素α抗病毒治疗后期(血清HBV-DNA阴转后)与肝细胞内HBV cccDNA具有相关性,血清HBsAg定量变化可作为抗病毒治疗病毒学持续应答预测指标。

OBJECTIVE To explore the changes of HBV eecDNA, serum HBV-DNA, HBsAg, and alanine aminotransferase （ALT） in hepatocytes of patients with chronic hepatitis B after the treatment with interferon-a and analyze the correlation between the changes. METHODS A total of 31 cases of chronic hepatitis B, who were suitable for interferon therapy, were randomly enrolled in the study and were treated with interferon alfa for 48 weeks, then the HBV cccDNA in hepatoeytes, serum HBV-DNA, HBsAg, and ALT were detected before and after the treatment, and the statistical analysis was performed with the use of IBM SPSS Statistics（Version 20） software. RESULTS The HBV cccDNA has been detected from all liver specimens; the HBV eccDNA in hepatoeytes reduced by （2.52 1.60） log cps/cell, the serum HBV-DNA decreased by （1.51 1.02）log IU/mL, the level of ALT decreased by（100.8!63.1）U/L, and the serum HBsAg decreased by （1.18-＋-0.85）1og ng/mL; the baseline HBV cccDNA in hepatocytes was correlated with HBV-DNA（log（HBV-DNA/mL）- 3.55＋0.44 X log（HBV cccDNA/cell） ,R2 =0. 197, P0.01. After the interferon alfa therapy for 48 weeks, the HBV cccDNA in hepatocytes was related to the load of serum HBsAg （log （HBsAg/mL）= 4.23 ＋ 0. 78 5〈 log （HBV eccDNA/ cell） ,R2 =0. 616,P〈0.01. CONCLUSION The HBV cccDNA can be successfully detected from the liver tissueswith the use of quantitative PCR the 48-week therapy with interferon alfa for the chronic hepatitis B can reduce the HBV cccDNA in the liver tissues and decrease the serum viral loads as well as stabilize liver function there is correlation between the serum HBsAg and the HBV cceDNA in hepatocytes at the late stage of interferon alfa therapy the quantitative change of serum HBsAg can serve as an indicator for prediction of sustained virologic response to antiviral therapy.