Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level
Abstract
CONTEXT: Serum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B. OBJECTIVE: To evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992. MAIN OUTCOME MEASURE: Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems. RESULTS: There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41,779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100,000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100,000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P<.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk. CONCLUSION: Elevated serum HBV DNA level (> or =10,000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.
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HBV titres in patients positively correlate with risk for disease progression and hepatocellular carcinoma development.
“Notably, HBV titres in patients positively correlate with risk for disease progression and HCC development69.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [69]
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- Authors
- Chen, C.-J.
- Affiliations
- National Taiwan University (TW)
- Corresponding author
- Chen, Chien-Jen
- ORCID
- Chen, Chien-Jen
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2006-01-04
- Volume
- 295
- Issue
- 1
- Pages
- 65
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2104389844
- Cited by
- 3,140
- References
- 21
- Citations by year
- 2026: 56 · 2025: 75 · 2024: 91 · 2023: 134 · 2022: 138 · 2021: 144 · 2020: 141 · 2019: 125 · 2018: 136 · 2017: 155 · 2016: 184 · 2015: 202 · 2014: 189 · 2013: 189 · 2012: 191
- FWCI
- 149.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Keywords
- hepatocellular carcinoma, hepatitis B virus, serum HBV DNA, viral replication, chronic hepatitis B, cancer risk prediction, dose-response relationship, liver cirrhosis, alanine aminotransferase, cancer incidence
- MeSH terms
- Adult, Alanine Transaminase, DNA, Viral, Female, Hepatitis B e Antigens, Hepatitis B virus, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Prospective Studies, Risk Factors, Taiwan, Incidence, Proportional Hazards Models, Hepatitis B, Chronic
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