Non-Linear Association Between Liver Fibrosis Scores and Viral Load in Patients with Chronic Hepatitis B

Kim, Gi-Ae; Choi, Seung Won; Han, Seungbong; Lim, Young-Suk

doi:.0..

Original Article

Non-Linear Association Between Liver Fibrosis Scores and Viral Load in Patients with Chronic Hepatitis B

Gi-Ae Kim¹, Seung Won Choi², Seungbong Han³, Young-Suk Lim⁴

¹Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea
²University of Ulsan College of Medicine, Seoul, Republic of Korea
³Department of Biostatistics, Korea University, Republic of Korea
⁴Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Correspondence :

Young-Suk Lim ,
Tel: +82-02-3010-5933, Fax: +82-02-485-5782, Email: limys@amc.seoul.kr

Received: April 12, 2024 Revised: July 13, 2024 Accepted: July 18, 2024
*Gi-Ae Kim and Seung Won Choi contributed equally to this work.

ABSTRACT

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.
Conclusions
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.

KeyWords: hepatitis B virus; hepatocellular carcinoma; liver cancer; liver fibrosis score