IMPACT OF HBEAG ON HEPATOCELLULAR CARCINOMA RISK DURING ORAL ANTIVIRAL TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS B

초록

Background: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of oral antiviral treatment on the risk of HCC. Methods: The incidence of HCC was evaluated in Korean chronic hepatitis B (CHB) patients who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. Different baseline characteristics were adjusted or balanced by multivariable analyses or propensity score-based methods. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. Results: A total of 9,143 Korean patients (mean age=49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median=5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg-positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg-positivity was independently associated with a lower risk of HCC development in multivariable (adjusted hazard ratio [aHR]=0.41, 95% confidence interval [CI]=0.26–0.66), propensity score matching (aHR=0.46, 95% CI=0.28–0.76), and inverse probability weighting analyses (aHR=0.44, 95% CI=0.28–0.70). In the Caucasian cohort (n=719, mean age=51.8 years, HBeAg-positive=20.3%, cirrhosis=34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR=0.21, 95% CI=0.00–1.67). Conclusion: This multinational cohort study implies that HBeAg-positivity at the onset of antiviral seems to be an independent factor associated with a lower risk of HCC in CHB patients without cirrhosis, but not in those with cirrhosis.