Public Health Nutrition

Research Paper

Impact of chewing betel-nut (Areca catechu) on liver cirrhosis and hepatocellular carcinoma: a population-based study from an area with a high prevalence of hepatitis B and C infections

Grace Hui-Min Wua1, Barbara J Bouchera2, Yueh-Hsia Chiua1, Chao-Sheng Liaoa3 and Tony Hsiu-Hsi Chena1 c1

a1 Division of Biostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Room 521, No. 17 Hsuchow Road, Taipei, Taiwan

a2 Center for Diabetes & Metabolic Medicine, Bart’s and The London School of Medicine & Dentistry, London, UK

a3 Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan


Background 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.

Objective 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.

Subjects 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.

Results 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.

Conclusion 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.

(Received October 19 2007)

(Accepted February 14 2008)


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This article is Keelung Community-based Integrated Screening (KCIS) study no. 15.