Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B
Authors
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 ; Joon Yeul Nam ; Yun Bin Lee ; Yoon Jun Kim ; Jung-Hwan Yoon ; Fabien Zoulim ; Pietro Lampertico ; George N Dalekos ; Ramazan Idilman ; Vana Sypsa ; Thomas Berg ; Maria Buti ; Jose Luis Calleja ; John Goulis ; Spilios Manolakopoulos ; Harry LA Janssen ; George V Papatheodoridis ; Jeong-Hoon Lee
Citation
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, Vol.20(6) : 1343-1353, 2022-06
Antiviral Agents / therapeutic use ; Carcinoma, Hepatocellular* / etiology ; Cohort Studies ; Hepatitis B Antigens / therapeutic use ; Hepatitis B e Antigens ; Hepatitis B virus / genetics ; Hepatitis B, Chronic* / complications ; Hepatitis B, Chronic* / drug therapy ; Humans ; Liver Cirrhosis / complications ; Liver Neoplasms* / etiology ; Middle Aged
Keywords
Cumulative Incidence ; DNA ; Hepatitis B Virus ; Liver Cancer ; Neoplasm
Abstract
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 patients with chronic hepatitis B 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 9143 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 patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.