[NATAP] alcohol/tobacco/obesity & HCC

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Are alcohol, tobacco and obesity genuine risk factors for hepatocellular carcinoma?

Teh-Ia HuoabCorresponding Author Informationemail address, Jaw-Ching Wuac, Shou-Dong Leeab

a National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC

b Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC

c Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC

Journal of Hepatology

June 2005.

Dear Editor,

We have read with interest the paper published in a recent issue of the Journal of Hepatology [1]. It is an elegant case-controlled study, which looked at the role of alcohol, tobacco and obesity as a risk factor of hepatocellular carcinoma (HCC). One of the interesting findings is that for patients with heavy alcohol consumption, the risk ratio for the development of HCC ranged from 5.7 to 23.8 depending on the status of the matched controls. The risk ratio of HCC was also comparably high, ranging from 4.9 to 63.7, for patients with heavy tobacco exposure. However, a major shortcoming of this study is that the status of viral hepatitis B and C has not been reported. It is well known that hepatitis B and C virus (HBV, HCV) are major risk factors for HCC formation. Failure to incorporate these two highly influential risk factors into analysis would potentially compromise their results and conclusions.

HCC is one of the most common malignant neoplasms worldwide, and the largest concentration of cases is in Asia [2]. Chronic HBV infection is highly prevalent in this area and is the predominant etiology of HCC. Our previous study indicated that among the Chinese patients with HCC, 75% were seropositive for HBV surface antigen (HBsAg) and 97% were seropositive for antibody to hepatitis B core antigen [3]. The prevalence of HCV infection was significantly higher in patients with HBsAg-negative HCC than those with HBsAg-positive HCC (37 versus 4%) [3]. In a large-scale prospective study from another independent group in Taiwan, the risk ratio for the development of HCC in HBsAg carriers was estimated to be between 9.6 and 60.2 depending on the status of hepatitis B e antigen, and the risk ratio among those with chronic HCV infection was estimated to be 2.7 [4]. It is noteworthy that the risk ratio of HCC in patients with heavy alcohol consumption and tobacco exposure was both only 1.5 (95% confidence interval: 1.0-2.2 for tobacco exposure and 1.0-2.3 for alcohol consumption) at a marginal statistical significance [4]. These data sources from different studies highly suggest a possible competition and interaction of the risk factors that were analyzed in different series. It is generally believed that HBV and HCV are genuine risk factors of HCC. Compared to the viral factor, tobacco exposure and alcohol use play only a minor role in inducing HCC formation. It would be quite difficult to interpret the statistical results and conclude that patients with tobacco or alcohol consumption are at a high risk for HCC without knowing the status of hepatitis B or C. In summary, inclusion of detailed information of underlying viral hepatitis is considered crucial to examine the potential risk factors of HCC because the possible carcinogenic effect of tobacco or alcohol might be masked in the presence of other stronger risk factors.

References

1. Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol. 2005;42:218-224. Abstract | Full Text | PDF (124 KB) | MEDLINE | CrossRef

2. Okuda K. Hepatocellular carcinoma: recent progress. Hepatology. 1992;15:948-963. MEDLINE

3. Lee SD, Lee FY, Wu JC, Hwang SJ, Wang SS, Lo KJ. The prevalence of anti-hepatitis C virus among Chinese patients with hepatocellular carcinoma. Cancer. 1992;69:342-345. MEDLINE

4. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al.. Hepatitis B e antigen and the risk of hepatocellular carcinoma. New Engl J Med. 2002;347:168-174. CrossRef