Impact of baseline viral load on hepatocellular carcinoma risk during antiviral treatment in non-cirrhotic patients with HBeAg-positive chronic hepatitis B

Abstract

Background and aims: Early initiation of anti-viral treatment with high viral load is highly controversial in HBeAg-positive patients with chronic hepatitis B (CHB). Here, we investigated the impact of hepatitis B virus (HBV) DNA levels at the onset of antiviral treatment on the on-treatment risk of hepatocellular carcinoma (HCC) in non-cirrhotic patients with HBeAg-positive CHB.

Method: We conducted a multicenter cohort study including entecavir- or tenofovir-treated non-cirrhotic patients with HBeAg-positive CHB and baseline HBV DNA levels ≥5.00 log10 IU/ml at three centers in Korea between January 2007 and December 2016. We compared the on-treatment risk of HCC between high viral load (HBV DNA levels ≥8.00 log10 IU/ml) and moderate viral load (5.00–7.99 log10 IU/ml) groups.

Results: Of 2, 073 patients, 1, 108 patients were classified as high viral load group and 965 patients were moderate viral load group. After propensity score (PS)-matching, 930 pairs of patients were generated with well-balanced baseline characteristics. In the entire cohort, HCC was developed in 10 patients (0.15 per 100 person-years) in the high viral load group compared with 37 patients (0.67 per 100 person-years) in the moderate viral load group, during a median 5.7 years of antiviral treatment. Patients with moderate viral load at baseline showed a significantly higher HCC incidence than those with high viral load in both the entire and PS-matched cohorts by Kaplan-Meier analysis ( p <0.001 for both; Figure). By multivariable analysis, the moderate viral load group had a significantly higher risk of HCC (hazard ratio, 3.48; 95% confidence interval, 1.72–7.06; P < 0.001) than the high viral load group, which was also consistently observed in the PS-weighted, PS-matched, and competing risk analyses.

Conclusion: In non-cirrhotic patients with HBeAg-positive CHB, decreased HBV DNA levels at baseline was associated with a significantly high risk of HCC during antiviral treatment. Early initiation of antiviral treatment with a high viral load (≥8.00 log10 IU/ml) would retain a low on-treatment risk of HCC in HBeAg- positive CHB patients.