The Effect of Coffee Consumption on the Development of Hepatocellular Carcinoma in Hepatitis B Virus Endemic Area

Eun Sun Jang; Sook-Hyang Jeong; Sang Hyub Lee; Sung Ho Hwang; So Yeon Ahn; Jaebong Lee; Young Soo Park; Jin Hyoek Hwang; Jin-Wook Kim; Nayoung Kim; Dong Ho Lee; Hyun Young Kim


Liver International. 2013;33(7):1092-1099. 

In This Article

Abstract and Introduction


Background & Aims Coffee consumption is inversely related to the risk of cirrhosis or hepatocellular carcinoma (HCC). However, the protective effect of coffee drinking against the risk of HCC was not established in HBV-prevalent region. To elucidate the relationship between lifetime coffee consumption and the risk of HCC development under the consideration of replication status of HBV.
Methods A hospital-based case–control study was performed in 1364 subjects. A total of 258 HCC patients, 480 health-check examinees (control 1, HCE) and 626 patients with chronic liver disease other than HCC (control 2, CLD) were interviewed on smoking, alcohol and coffee drinking using a standardized questionnaire. HBV e-antigen (HBeAg) status and serum HBV DNA levels were measured in patients infected with HBV.
Results After adjustment for age, gender, obesity, DM, presence of hepatitis virus (except for HCE) and lifetime alcohol drinking/smoking, a high lifetime coffee consumption (≥20 000 cups) was an independent protective factor against HCC, in each analyses using healthy and risky control groups respectively (HCE group, OR 0.56, 95% CI 0.33–0.95; CLD group, OR 0.55, 95% CI 0.36–0.85). However, the high coffee consumption did not affect the HCC risk in patients with HBV (OR 0.64, 95% CI 0.36–1.14) after adjustment for HBeAg status, serum HBV DNA level and antiviral therapy.
Conclusions A high lifetime coffee consumption was negatively associated with a HCC development. However, this difference of coffee exposure with the HCC group was reduced in chronic hepatitis B patients by the dominant role of viral replication.


Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide. According to the GLOBOCAN report, there were estimated 749 thousands liver cancer cases and 695 thousands liver cancer-related death in 2008.[1] Because liver cancer represents large health and economic burdens on the society, many investigators have exerted efforts to prevent the development of the cancer. So far, several host factors such as age, sex, obesity or diabetes and environmental factors (hepatitis viruses, alcohol, aflatoxin, etc.) have been documented to increase the risk of hepatocellular carcinoma (HCC).[2,4]

It has been suggested that coffee may have a beneficial effect on the liver function. Coffee drinkers have lower liver enzyme levels including serum alanine aminotransferase or gamma-glutamyl transferase compared to the non-consumers.[5,6] Moreover, coffee consumption reduces cirrhosis,[7] the strongest risk factor of HCC.[8] Many epidemiological studies have reported that coffee consumption has an inverse relationship with HCC development[9] as well as with cirrhosis. However, those studies were reported mostly from North America, Europe and Japan, whereas studies from Asian countries where epidemiology and clinical features are different from the Western countries were sparse.[10] In addition, most studies analysed recent (1–2 years prior) status of coffee drinking rather than lifetime amount, although hepatic carcinogenesis is a long-term process.

Hepatitis virus infection is an well-established risk factor for HCC.[11] According to a large-scale prospective study, the risk of HCC development among hepatitis B virus (HBV) carriers of the western countries are as high as that of the HBV-endemic countries.[12] Nevertheless, several previous studies on the effect of coffee consumption in HCC risk did not assort the viral status of subjects with chronic liver disease.[13,16] Moreover, most cohort studies on the effect of coffee on HCC risk considering underlying viral aetiologies have been published from hepatitis C virus (HCV) predominant regions.[17,19] Especially, hepatitis B e-antigen (HBeAg) status[20] and serum HBV deoxyribonucleic acid (DNA) level[21] have been documented as important determinants of HCC risk among chronic hepatitis B (CHB) patients. However, previous studies showing a protective effect of coffee against HCC did not mention viral factors except hepatitis B surface antigen (HBsAg) status.

Thus, this study was conducted to elucidate the relationship between lifetime coffee consumption and the risk of HCC development in a HBV-prevalent region using a case–control design with both healthy and chronic liver disease control groups. Additionally, we evaluated whether the effect of coffee drinking was independent of the replication status of HBV in chronic liver disease patients.