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

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.

Automated summary

The association between baseline HBV DNA levels and risk of hepatocellular carcinoma (HCC) remains unclear. This multicenter cohort study showed that in HBeAg-positive, noncirrhotic adult patients with chronic hepatitis B (CHB), decreasing baseline HBV DNA levels were associated with an incremental increase in on-treatment HCC risk.