聚乙二醇干扰素 α-2a 和阿德福韦酯治疗慢性乙型肝炎患者的肝内反应标志物。

Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir.

机构信息

Departments of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

出版信息

J Gastroenterol Hepatol. 2011 Oct;26(10):1527-35. doi: 10.1111/j.1440-1746.2011.06766.x.

DOI:10.1111/j.1440-1746.2011.06766.x

PMID:21557773

Abstract

BACKGROUND AND AIM

We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg-interferon and adefovir for 48 weeks.

METHODS

Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment.

RESULTS

Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow-up (week 72). At end of treatment, intrahepatic cccDNA and total intrahepatic HBV DNA in HBeAg positive patients were significantly lower in patients with HBeAg seroconversion (P = 0.016 and P = 0.010) with positive predictive values (PPV) for SVR of 80% and 80%, respectively. In HBeAg negative patients, intrahepatic cccDNA and total intrahepatic HBV DNA had declined significantly at end of treatment (P = 0.035 and P = 0.041) and corresponding PPV for SVR was 73% and 82%. In HBeAg positive patients, median proportion of HBcAg positive hepatocytes declined significantly (P = 0.002) at end of treatment. In HBeAg negative patients, the proportion of HBsAg positive hepatocytes had declined significantly at end of treatment (P = 0.0009). Using HBsAg ≤ 7.5% as a limit, PPV for SVR in HBeAg negative patients was 83%.

CONCLUSIONS

At end of treatment in HBeAg positive patients, intrahepatic cccDNA and total intrahepatic HBV DNA were predictive for SVR. In HBeAg negative patients a proportion of < 7.5% HBsAg positive hepatocytes at end of treatment was a strong predictor for SVR.

摘要

背景和目的

我们研究了在接受聚乙二醇干扰素和阿德福韦酯治疗 48 周的慢性乙型肝炎病毒（HBV）患者中，肝内标志物是否可以预测应答。

方法

在 16 例乙型肝炎 e 抗原（HBeAg）阳性和 24 例 HBeAg 阴性患者中，于基线和治疗结束时测量肝内共价闭合环状 DNA（cccDNA）、总肝内 HBV DNA 以及乙型肝炎表面抗原（HBsAg）和乙型肝炎核心抗原（HBcAg）阳性肝细胞的比例。

结果

基线肝内标志物与持续病毒学应答（SVR）无关，定义为治疗结束时 HBV DNA < 2000 IU/ml 和持续正常丙氨酸氨基转移酶水平（随访结束时第 72 周）。在治疗结束时，HBeAg 阳性患者中 HBeAg 血清学转换患者的肝内 cccDNA 和总肝内 HBV DNA 显著降低（P = 0.016 和 P = 0.010），SVR 的阳性预测值（PPV）分别为 80%和 80%。在 HBeAg 阴性患者中，治疗结束时肝内 cccDNA 和总肝内 HBV DNA 显著下降（P = 0.035 和 P = 0.041），SVR 的相应 PPV 为 73%和 82%。在 HBeAg 阳性患者中，治疗结束时 HBcAg 阳性肝细胞的中位数显著下降（P = 0.002）。在 HBeAg 阴性患者中，治疗结束时 HBsAg 阳性肝细胞的比例显著下降（P = 0.0009）。使用 HBsAg ≤ 7.5%作为界限，HBeAg 阴性患者的 SVR 的 PPV 为 83%。