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Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

Abstract
The study was designed to investigate whether serum hepatitis B virus (HBV) RNA is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n = 82) and 96 weeks (n = 62) after treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r = 0.36, P < 0.01) than with serum HBV RNA levels (r = 0.25, P = 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg (r = 0.15, P = 0.17) or HBeAg (r = 0.07, P = 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r = 0.39, P < 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P > 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum HBsAg levels than with the decreases in the levels of the other markers (for the HBsAg decline, r = 0.38, P < 0.01; for the HBV DNA decline, r = 0.35, P = 0.01; for the HBV RNA decline, r = 0.28, P < 0.05; for the HBeAg decline, r = 0.18, P = 0.19). In conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at 96 weeks after treatment, respectively.
AuthorsYuhua Gao, Yutang Li, Qinghua Meng, Zhanqing Zhang, Ping Zhao, Qinghua Shang, Yue Li, Mingze Su, Tong Li, Xueen Liu, Hui Zhuang
JournalJournal of clinical microbiology (J Clin Microbiol) Vol. 55 Issue 10 Pg. 2972-2982 (10 2017) ISSN: 1098-660X [Electronic] United States
PMID28747369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 American Society for Microbiology.
Chemical References
  • Antiviral Agents
  • DNA, Circular
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Nucleosides
  • Nucleotides
  • RNA, Viral
Topics
  • Adolescent
  • Adult
  • Antiviral Agents (therapeutic use)
  • DNA, Circular (blood, genetics)
  • DNA, Viral (blood, genetics)
  • Female
  • Hepatitis B Surface Antigens (blood)
  • Hepatitis B e Antigens (blood)
  • Hepatitis B virus (genetics, isolation & purification)
  • Hepatitis B, Chronic (diagnosis, virology)
  • Humans
  • Liver (virology)
  • Male
  • Middle Aged
  • Nucleosides (therapeutic use)
  • Nucleotides (therapeutic use)
  • RNA, Viral (blood, genetics)
  • Young Adult

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