Rapid Communication
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2008; 14(8): 1268-1273
Published online Feb 28, 2008. doi: 10.3748/wjg.14.1268
Effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA in HBeAg-positive chronic hepatitis B patients
Hai-Ying Lu, Li-Wei Zhuang, Yan-Yan Yu, Chong-Wen Si, Jun Li, Jian-Jun Zhang, Zheng Zeng, Xin-Yue Chen, Zhong-Hou Han, Yong Chen
Hai-Ying Lu, Li-Wei Zhuang, Yan-Yan Yu, Chong-Wen Si, Jun Li, Zheng Zeng, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
Jian-Jun Zhang, Beijing Zhongfuyouxin, Beijing 100085, China
Xin-Yue Chen, Beijing You'an Hospital, Beijing 100054, China
Zhong-Hou Han, Qinhuangdao Third Hospital, Qinhuangdao 066000, Hebei Province, China
Yong Chen, Huai'an Infectious Disease Hospital, Huai’an 223300, Jiangsu Province, China
Author contributions: Lu HY and Zhang LW wrote the paper and contributed equally to this work; Yu YY, Si CW and Zeng Z designed the research; Lu HY, Zhang LW, Li J and Zhang JJ performed the research; Chen XY, Han ZH and Chen Y recorded the clinical data.
Correspondence to: Professor Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. yyy@bjmu.edu.cn
Telephone: +86-10-66551122-2370
Fax: +86-10-66551808
Received: November 7, 2007
Revised: January 8, 2008
Published online: February 28, 2008
Abstract

AIM: To evaluate the effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA (ccc DNA) in HBeAg-positive chronic hepatitis B patients.

METHODS: Seventy-one patients received lamivudine (n = 35), or sequential therapy with lamivudine- interferon alpha 2b (IFN-α 2b, n = 24) for 48 wk, or IFN-α 2b (n = 12) for 24 wk. All subjects were followed up for 24 wk. Intrahepatic ccc DNA was measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.

RESULTS: Sequential lamivudine- INF-α therapy, lamivudine and INF-α monotherapy reduced ccc DNA of 1.7 log, 1.4 log and 0.8 log, respectively (P < 0.05). Seventeen out of the 71 patients developed HBeAg seroconversion, the reduction of ccc DNA in the HBeAg seroconversion patients was more significant than that in the HBeAg positive patients (3.0 log vs 1.6 log, P = 0.0407). Twenty-four weeks after antiviral therapy withdrawal, 16 patients had a sustained virological response, the baseline intrahepatic ccc DNA in the patients with a sustained virological response was significantly lower than that in the patients with virological rebound (4.6 log vs 5.4 log, P = 0.0472). HBV genotype C accounted for 85.9% (n = 61), and genotype B for 14.1% (n = 10), respectively, in the 71 patients. There was no significant difference in the change of ccc DNA level between HBV genotypes C and B (2.1 log vs 1.9 log).

CONCLUSION: Forty-eight week sequential lamivudine-INF-α therapy and lamivudine monotherapy reduce ccc DNA more significantly than 24-wk INF-α monotherapy. Low baseline intrahepatic ccc DNA level may predict the long-term efficacy of antiviral treatment. HBV genotypes C and B have no obvious influence on ccc DNA load.

Keywords: Covalently closed circular DNA; Hepatitis B virus; Sequential therapy; Lamivudine; Interferon