Sir,

As a coffee-drinking virologist, I read Leung et al's report on coffee consumption and risk of hepatocellular carcinoma (HCC) with interest[1].

The authors excluded those "under medication for liver diseases". It is a reasonable assumption that this means that patients who were receiving antiviral therapy for hepatitis B virus (HBV), e.g. lamivudine, entecavir etc. were excluded. Because patients with a higher risk of developing HCC tend to receive drug therapy for HBV[2], there is a risk that the exclusion of HBV carriers on anti-HBV therapy may have introduced a bias into the non-HCC control group.

Healthy HBV carriers in whom antiviral therapy is not indicated may be fundamentally different from patients with HBV-related HCC. One would expect patients who do not meet criteria for initiating antiviral therapy to have a better prognosis i.e. are less likely to develop HCC.

Leung et al acknowledge some limitations of this study e.g. lack of HBV viral load data and alanine transaminase (ALT) level. However, patients' hepatitis B e antigen status, one measure of HBV infectivity and an independent predictor for progression to HCC[3], is also missing. I would suggest these limitations have been underplayed.

The absence of HBV viral load data, e antigen status and ALT levels are significant omissions and linked to my first point about excluding patients on "medication for liver disease". These variables are both prognostic indicators and indicators for the necessity for HBV treatment.

Finally, it would be of interest to know the hepatitis C (HCV) and HIV status of the patients studied, as these do affect the prognosis in hepatitis B carriers. I concede that both HCV and HIV seem to be relatively uncommon in Hong Kong[4,5]. As this information was not provided, yet more potential confounding variables have been left unaddressed.

The apparent exclusions and omissions detailed above leave considerable room for doubt about the comparability of the cases and controls and thus of the conclusions drawn.

The proposition that coffee consumption reduces the risk of HCC developing in HBV carriers is a seductive one. It would be an almost ideal public health intervention, as coffee is widely available, economical, given that the cost is borne by patients and there are few significant side effects with light or moderate consumption.

Unfortunately, it is difficult to concur with the author's conclusion that moderate coffee consumption significantly reduces the risk of HCC in HBV carriers based upon the findings of this study.

References:

1. Leung W W-M, Ho SC et al. Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a case- control study. J Epidemiol Community Health 2011;65:556-558

2. Sung JJ, Amarpurkar D et al. Treatment of chronic hepatitis B in Asia-Pacific countries: is the Asia-Pacific consensus statement being followed? Antivir Ther 2010;15(4):607-16

3. Yang HI, Lu SN, Liaw YF et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N England J Med 2002;347(3):168-74

4. Hong Kong Department of Health. Viral Hepatitis Preventive Service website. http://www.info.gov.hk/hepatitis/english/hep_c_set.htm (accessed 18/7/11)

5. Hong Kong Department of Health. HIV/AIDS Situation in Hong Kong (2005) factsheet. http://www.info.gov.hk/aids/pdf/g154.pdf (accessed 18/7/11)

Conflict of Interest:

None declared