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Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients with Chronic Hepatitis B
Clinical Gastroenterology and Hepatology  (IF11.382),  Pub Date : 2021-09-06, DOI: 10.1016/j.cgh.2021.09.001
Heejoon Jang, Jun Sik Yoon, Soo Young Park, Han Ah Lee, Myoung-jin Jang, Seung Up Kim, Dong Hyun Sinn, Yeon Seok Seo, Hwi Young Kim, Sung Eun Kim, Dae Won Jun, Eileen L. Yoon, Joo Hyun Sohn, Sang Bong Ahn, Jae-Jun Shim, Soung Won Jeong, Yong Kyun Cho, Hyoung Su Kim, Jeong-Hoon Lee

BACKGROUND & AIMS

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 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. 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 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).

CONCLUSIONS

This multinational cohort study implies that HBeAg-positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in CHB patients without cirrhosis, but not in those with cirrhosis.