Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B

Abstract

BACKGROUND. It 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). METHODS. We 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 log(10) 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. RESULTS. During a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 personyears). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log(10) IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00-5.99 log(10) 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 log(10) IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00-7.99 log(10) IU/mL, 6.00-6.99 log(10) IU/mL, or 5.00-5.99 log(10) IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively. CONCLUSION. On-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log(10) 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 log(10) IU/mL) may maintain the lowest risk of HCC for those patients.