Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy
Open accessAbstract
Background & aims This study aimed to determine whether intrahepatic hepatitis B virus (HBV) covalently closed circular (ccc) DNA and total HBV DNA levels at the end of therapy would predict sustained response to therapy.Methods Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients receiving either lamivudine monotherapy or combination of peginterferon and lamivudine had liver biopsy at the end of 1 year therapy and were followed for 52 more weeks after cessation of therapy. Serum HBV DNA, intrahepatic HBV ccc DNA, and total HBV DNA levels were determined.Results Forty-seven patients, including 34 males and 13 females, were studied. Twenty-seven patients received combination therapy, and 20 patients received lamivudine monotherapy. Twenty-nine patients had end-of-treatment virologic response, and 15 patients had sustained response 52 weeks after therapy. At the end of treatment, log serum HBV DNA levels correlated well with log intrahepatic HBV cccDNA and log intrahepatic total HBV DNA levels. Log intrahepatic cccDNA and log intrahepatic total DNA levels were significantly lower among patients with sustained virologic response. The adjusted odds ratio for log cccDNA was 5.3 (95% CI: 1.5-18.2, P = .009) and, for log intrahepatic HBV DNA, was 4.4 (95% CI: 1.3-14.7, P = .015) to predict sustained virologic response. Using log cccDNA at -0.80 copies/genome equivalent as cutoff, the sensitivity, specificity, and positive and negative predictive values and accuracy of predicting sustained virologic response were 73%, 78%, 56%, 86%, and 77% respectively.Conclusions Intrahepatic HBV cccDNA and intrahepatic total HBV DNA levels at the end of therapy are superior to serum HBV DNA as surrogates of sustained virologic response.
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HBV cccDNA exhibits staggering stability and declines slowly under antiviral therapy, representing a major barrier to viral eradication.
“Moreover, HBV cccDNA exhibits staggering stability and declines slowly under antiviral therapy, thus representing a major barrier to viral eradication.3,4,5,6”
From The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo (2014) · cites this paper as [6]
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- Authors
- Sung, J. J. Y., Wong, M.-L., Bowden, S., Liew, C.-T., Hui, A. Y., Wong, V. W. S., Leung, N. W. Y., Locarnini, S., & Chan, H. L. Y.
- Affiliations
- Chinese University of Hong Kong (HK)
- Victorian Infectious Diseases Reference Laboratory (AU)
- Alice Ho Miu Ling Nethersole Hospital (CN)
- Corresponding author
- Sung, Joseph J.Y.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 128
- Issue
- 7
- Pages
- 1890-1897
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1992475294
- Cited by
- 218
- References
- 32
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 10 · 2016: 12 · 2015: 12 · 2014: 16 · 2013: 14 · 2012: 12
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese University of Hong Kong
- Topics
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatitis B virus, covalently closed circular DNA, chronic hepatitis B, sustained virological response, lamivudine, pegylated interferon, HBeAg-positive, prognostic factors, serum HBV DNA
- MeSH terms
- Interferon alpha-2, Adult, Antiviral Agents, DNA, Circular, DNA, Viral, Drug Therapy, Combination, Female, Hepatitis B virus, Humans, Liver, Male, Polyethylene Glycols, Predictive Value of Tests, Recombinant Proteins, Sensitivity and Specificity, Polymerase Chain Reaction, Treatment Outcome, Interferon-alpha, Lamivudine, Hepatitis B, Chronic
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