BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV)
DNA at baseline affects the on-treatment risk of
hepatocellular carcinoma (HCC) in
hepatitis B e antigen-positive (
HBeAg-positive), noncirrhotic patients with
chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073
entecavir- or
tenofovir-treated,
HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV
DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV
DNA levels.RESULTSDuring a median 5.7 years of continuous
antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV
DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV
DNA levels of 5.00-5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV
DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV
DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV
DNA levels of 7.00-7.99 log10 IU/mL, 6.00-6.99 log10 IU/mL, or 5.00-5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV
DNA levels in the range of 5.00 log10 IU/mL or higher in
HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of
antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for
Cancer Control through the National
Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.