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. 2025 Jul-Aug;15(4):102540.
doi: 10.1016/j.jceh.2025.102540. Epub 2025 Mar 3.

No Differences in Risk of Cirrhosis or Hepatocellular Carcinoma Among Treatment Naïve Chronic Hepatitis B Patients by Baseline Hepatitis B Viral Load: A Propensity Score Weighted Analysis

Zeyuan Yang  1 , Ramsey C Cheung  1   2 , Janice H Jou  3   4 , Joseph K Lim  5 , Robert J Wong  1   2
Affiliations

No Differences in Risk of Cirrhosis or Hepatocellular Carcinoma Among Treatment Naïve Chronic Hepatitis B Patients by Baseline Hepatitis B Viral Load: A Propensity Score Weighted Analysis

Zeyuan Yang et al. J Clin Exp Hepatol. 2025 Jul-Aug.

Abstract

Background and objectives: Previous studies among Korean adults with treatment-naïve chronic hepatitis B (CHB) observed paradoxical relationships between baseline hepatitis B virus (HBV) DNA and risk of hepatocellular carcinoma (HCC). However, these observations have not been validated in Western cohorts. We aim to evaluate the longitudinal risk of cirrhosis or HCC among a national cohort of treatment-naïve patients with noncirrhotic chronic HBV.

Methods: Using a national cohort of U.S. Veterans with CHB (with baseline HBV DNA ≥2000 IU/mL) from 1/1/2020 to 3/31/2024, we evaluated the long-term risk of cirrhosis or HCC stratified by baseline high HBV DNA (>6.00 log10 IU/mL) or moderate HBV DNA (2000-6.00 log10 IU/mL). We applied propensity score weighting methods to adjust for baseline differences between the two groups.

Results: A total of 1198 noncirrhotic treatment-naïve CHB patients with HBV DNA ≥2000 IU/mL were identified (90.7% were men, 41.7% African American, 29.6% non-Hispanic white, 18.2% Asian, mean age was 54.7 years, 27.9% were HBeAg positive). After propensity score weighting was applied, no significant differences in the incidence of cirrhosis or HCC were observed between CHB patients with moderate vs. high baseline HBV DNA (cirrhosis: 1.02 (95% CI: 0.83-1.25) vs. 1.19 per 100 person-years (95% CI: 0.94-1.51); HR 0.93, 95% CI: 0.68-1.28, P = 0.66; HCC: 0.34 (95% CI: 0.24-0.48) vs. 0.29 per 100 person-years (95% CI: 0.18-0.46); HR 1.02, 95% CI: 1.83, P = 0.95).

Conclusions: Among a national cohort of Western, predominantly non-Asian patients with treatment-naïve CHB, no significant differences in risk of cirrhosis or HCC were observed by baseline HBV DNA. These data suggest that some epidemiological trends and associations observed in Asian CHB populations may not necessarily be generalizable to non-Asian cohorts with different modes of transmission, risk factors, and virus-specific characteristics.

Keywords: HBV; HBV DNA; cirrhosis; hepatocellular carcinoma; veterans.

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Conflict of interest statement

ZY: No disclosures. RC: No disclosures. JJ: received research grants from Gilead Sciences. JL: received research grants from Gilead, Intercept, Inventiva, Novo Nordisk, Pfizer, and Viking; serves as consultant for Gilead Sciences. RW: Research funding (to his institution) from Gilead Sciences, Exact Sciences, Theratechnologies, and Durect Corporation; serves as consultant (without compensation) for Gilead Sciences.

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