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Original research
Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B
  1. Won-Mook Choi1,
  2. Gi-Ae Kim2,
  3. Jonggi Choi1,
  4. Gwang Hyeon Choi3,
  5. Yun Bin Lee4,
  6. Dong Hyun Sinn5,
  7. Young-Suk Lim1
  1. 1Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  2. 2Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea
  3. 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, South Korea
  4. 4Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
  5. 5Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  1. Correspondence to Professor Young-Suk Lim, Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea (the Republic of); limys{at}


Objective The association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in CHB patients without cirrhosis.

Design Using a multicentre historical cohort study including 4693 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive, adult CHB patients without cirrhosis who initiated antiviral treatment, HCC risk was estimated by baseline HBV viral load as a categorical variable.

Results During a median of 7.6 years of antiviral treatment, 193 patients developed HCC (0.53 per 100 person- years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a non-linear, parabolic pattern. Patients with moderate baseline viral loads (5.00–7.99 log10 IU/mL) exhibited the highest HCC risk (HR, 2.60; p<0.001), followed by those with low viral loads (3.30–4.99 log10 IU/mL; HR, 1.66; p=0.11). Patients with high viral loads (≥8.00 log10 IU/mL) presented the lowest HCC risk. Particularly, patients with baseline HBV DNA levels 6.00–6.99 log10 IU/mL had the highest on-treatment HCC risk (HR, 3.36; p<0.001) compared with those with baseline HBV DNA levels≥8.00 log10 IU/mL. These findings were more prominent among HBeAg-positive patients, younger patients, or those with less advanced hepatic fibrosis.

Conclusion Patients with moderate baseline viral load, particularly around 6 log10 IU/mL, demonstrated the highest on-treatment HCC risk, despite long-term antiviral treatment. Early initiation of antiviral treatment, tailored to viral load, should be considered to minimise HCC risk in adult CHB patients without cirrhosis.


Data availability statement

Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.

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Data availability statement

Data are available upon reasonable request. Data generated or analysed during the study are available from the corresponding author by request.

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  • Contributors Guarantor: The corresponding author (Y-SL) has full access to all the data used in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design, administrative support, manuscript writing: W-MC and Y-SL. Financial support: Y-SL. Collection and assembly of data: W-MC, G-AK, JC, GHC, YBL, DHS. Data analysis and interpretation: all authors. Final approval of manuscript, accountable for all aspects of the work: all authors.

  • Funding Korean government. There was no industry involvement in the design, conduct, or analysis of the study. This study was supported by grants from the Patient-Centered Clinical Research Coordinating Center (PACEN; grant number HC20C0062) of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center (grant number: HA21C0110), funded by the Ministry of Health & Welfare, Republic of Korea.

  • Disclaimer The funding sources had no role in the design of this study, its execution, analyses, interpretation of the data, or decision to submit the results.

  • Competing interests Y-S Lim is an advisory board member of Gilead Sciences and receives investigator-initiated research funding from Gilead Sciences. All other authors have declared that no conflict of interest exists.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.