Chewing betel-nuts (Areca catechu) is carcinogenic but the risk for hepatocellular carcinoma (HCC) and liver cirrhosis (LC) is little considered. Worldwide 600 million people chew betel, including emigrants from palm-growing countries.

We aimed to assess the relationships and dose–response effects of betel chewing on LC and HCC risks, since habit cessation could reduce the increased risks of HCC and LC found in such communities.

Screening 60 326 subjects aged 30–79 years in a population-based study in Taiwan identified LC in 588 and HCC in 131 subjects. Demographic features, hepatitis B/C infections, other risk factors and betel chewing were noted. Multiple Cox regression models were used to assess independent relationships, interactions and synergisms between age, betel chewing and hepatitis B/C.

Betel chewing increased LC and HCC risk 4·25-fold (95 % CI 2·9, 6·2) in current chewers and 1·89-fold (95 % CI 1·13, 3·16) in ex-chewers v. never-chewers, with dose effects for quantity, duration and cumulative exposure in chewers. Subjects without hepatitis B/C infections had 5·0-fold (95 % CI 2·87, 9·03) increased risk of LC/HCC v. never-chewers, and betel chewing had an additive synergistic effect on hepatitis B/C-related risks. Risk reduction with betel habit cessation could exceed that expected from immunization programmes for hepatitis B and C.

Increased risks of cirrhosis and hepatocellular cancer were found in betel chewers free of hepatitis B/C infection, and these risks were synergistically additive to those of hepatitis B/C infections. Estimated risk reduction from effective anti-betel chewing programmes would be sizeable.