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Updated: Jun 20, 2025

Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B
Gi-Ae Kim1, Seung Won Choi2, Seungbong Han3
1Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
Insights
Hepatitis B virus (HBV) DNA levels correlate with liver fibrosis scores in chronic hepatitis B (CHB) patients. Moderate viral loads showed the highest fibrosis scores, with HBV DNA predicting liver cancer risk independently.
Area of Science:
- Hepatology
- Virology
- Oncology
Background:
- Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are linked to hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients.
- The precise relationship between HBV DNA levels and liver fibrosis scores remains unclear.
Purpose of the Study:
- To investigate the association between HBV DNA levels and non-invasive liver fibrosis scores (APRI and FIB-4) in CHB patients.
- To determine if HBV DNA levels predict HCC risk independently of fibrosis scores.
Main Methods:
- A historical cohort of 6,949 non-cirrhotic Korean CHB patients was analyzed.
- General linear models assessed the association of baseline HBV DNA levels with APRI and FIB-4 scores.
- HCC development was tracked over a median 10-year follow-up.
Main Results:
- In HBeAg-negative patients, HBV DNA levels correlated linearly with APRI and FIB-4 scores.
- In HBeAg-positive patients, HBV DNA levels correlated inversely with APRI and FIB-4 scores.
- A non-linear parabolic relationship was observed across the cohort, with moderate viral loads (6-7 log10 IU/mL) showing the highest fibrosis scores.
- Higher APRI and FIB-4 scores were significantly associated with elevated HCC risk.
- HBV DNA level independently predicted HCC development, even after adjusting for fibrosis scores.
Conclusions:
- HBV viral load is significantly correlated with APRI and FIB-4 scores in CHB patients.
- HBV DNA levels are associated with HCC risk independently of APRI and FIB-4 scores.
- These findings suggest HBV DNA influences hepatocarcinogenesis through direct and indirect pathways.
Background/Aims:
Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.
Methods:
A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.
Results:
In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6-7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.
Conclusion:
HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.

