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Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a case–control study
  1. Winnie Wing-man Leung1,
  2. Suzanne C Ho1,2,
  3. Henry L Y Chan3,
  4. Vincent Wong3,
  5. Winnie Yeo4,
  6. Tony S K Mok4
  1. 1School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China
  2. 2Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China
  3. 3Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China
  4. 4Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China
  1. Correspondence to Ms Winnie W Leung, c/o Ms Joyce Leung, 2/F PEC Building, School of Public Health and Primary Care, Prince of Wales Hospital, Shatin, N.T., Hong Kong; winnieleung{at}cuhk.edu.hk

Abstract

Background Recent epidemiological studies have reported a dose-dependent protective effect of coffee on hepatocellular carcinoma (HCC) with risk reduction ranging from 30% to 80% in daily coffee drinkers compared with non-drinkers. This study examined whether coffee has a similar protective effect when consumed in moderate quantities in chronic hepatitis B virus (HBV) carriers, a group at high risk of developing liver cancer.

Methods A case–control design was employed. 234 HBV chronic carriers (109 cases and 125 controls) were recruited from the Prince of Wales Hospital in Hong Kong from December 2007 to May 2008. Data collection included review of medical records and face-to-face interview. Univariate and multivariate logistic regressions adjusting for age, gender, cigarette smoking, alcohol use, tea consumption and physical activity were conducted with dose–response analysis.

Results Moderate coffee consumption significantly reduced the risk of HCC by almost half (OR 0.54, 95% CI 0.30 to 0.97) with a significant dose–response effect (χ2=5.41, df=1, p=0.02), reducing the risk for moderate drinkers by 59% (OR 0.41, 95% CI 0.19 to 0.89).

Conclusion The findings provided evidence to support the protective effect of coffee consumption in moderate quantities in HBV chronic carriers.

  • cancer epidemiology
  • coffee
  • health-related behaviour
  • hepatitis
  • hepatitis B chronic carriers
  • hepatocellular carcinoma
  • protective factor

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Liver cancer ranks fourth in incidence and third in mortality among all cancers in Hong Kong.1 Recent epidemiological studies2–14 in Japan and Europe have suggested that coffee drinking lowers the risk of hepatocellular carcinoma (HCC) by 76% in those who consume five or more cups per day,9 with consistent results from meta-analyses.11 12 For hepatitis B virus (HBV) and hepatitis virus C chronic carriers, the protective effect of coffee ranged from 46%14 to 60%4 in daily drinkers. These studies were based on populations with heavy coffee consumption, with per capita consumption of 3.3, 5.3 and 5.5 kg, respectively, for Japanese, Italian and Greek, compared with only 1.1 kg in Hong Kong,15 where only 12% of its residents consume coffee habitually compared with the global average of 55%.16 The question of whether lower coffee consumption would offer the same protection against HCC was potentially important for this population, especially as HBV chronic carrier prevalence and liver cancer incidence rates were high in Hong Kong compared with other parts of the world. We hypothesised that HBV chronic carriers with occasional or moderate coffee consumption were at lower risk of HCC than those with no coffee-drinking habit.

Methods

A case–control study design was employed. All cases and controls were recruited from December 2007 to May 2008 during follow-up appointments at the Special Outpatient Clinic (SOPD) of the Prince of Wales Hospital in Hong Kong. Trained research assistants, blind to the research hypothesis, reviewed the medical record and administered a 15-min face-to-face interview with each participant during follow-up at the SOPD. The study was approved by the Joint CUHK-NTEC Clinical Research Ethics Committee, with informed consents from all participants.

Two hundred and thirty-four HBV carriers (109 cases, 125 controls) were entered into the study. Cases and controls were frequency matched by age group and gender distribution. Post-hoc analysis indicated no significant difference in alcohol use (χ2=1.66, df=1, p=0.44) and cigarette smoking (χ2=5.44, df=1, p=0.07) (table 1). HBV carrier status was defined as the detection of hepatitis B surface antigen in the blood samples of the participant. HCC was defined as the topography code C22.0 (ICD-O-3: C22.0, 817),17 and diagnosis was made based on the medical record for biopsy report, radiological finding of a space-occupying lesion in the liver and a raised α-fetoprotein ≥400 μg/l, or two coincidental radiological findings of a space-occupying lesion in the liver that has characteristic features of HCC. All subjects in the SOPD documented seropositive on hepatitis B surface antigen were eligible for inclusion; those under medication for liver diseases and with a previous history of cancer were excluded to control for confounding due to liver medication and cancer relapse.

Table 1

Demographic characteristics of cases and controls (N=234)

Exposure to coffee and potential confounders including smoking, alcohol use, tea consumption and physical activity (moderate intensity aerobic exercise) were tapped in terms of intensity (days per week of consumption; and amount per day) and life-time exposure (years of consumption). Univariate logistic regression was performed to examine the crude OR of HCC risk in HBV chronic carriers with a coffee consumption habit compared with those without. Multivariate logistic regression adjusting for potential confounders including age, gender, tea consumption, cigarette smoking, alcohol use and physical activity calculated as the product of intensity and life-time exposure was performed and compared with the crude OR to examine for confounding. The dose–response effect was tested using χ2 test for trend, with participants categorised into no coffee-drinking habit (<1 time/week), occasional coffee-drinkers (1–3 times/week), and moderate coffee-drinkers (≥4 times/week) to yield OR for the different dosages of coffee consumption.

Results

Univariate logistic regression yielded a crude OR of 0.59 (95% CI 0.34 to 1.04), indicating a marginally non-significant effect of coffee consumption on HCC diagnosis. After controlling for age, gender, tea and alcohol consumption, cigarette smoking and physical activity, multivariate logistic regression indicated a significant protective effect of coffee against HCC (OR 0.54, 95% CI 0.30 to 0.97; table 2). The χ2 test for trend suggested a dose–response relationship (χ2=5.41, df=1, p=0.02) with occasional coffee drinkers of 3 days per week or less having an OR of 0.57 (95% CI 0.24 to 1.36), and moderate coffee drinkers of four or more days per week having an OR of 0.41 (95% CI 0.19 to 0.89), compared with HBV carriers with no coffee-drinking habit.

Table 2

Logistic regression analyses of coffee consumption on HCC risk with OR, 95% CI and dose–response effect

Discussion

The present study examined whether occasional and moderate coffee drinking reduced the risk of HCC in chronic HBV carriers, a population at elevated risk of developing liver cancer. Results indicated that coffee drinking significantly reduced the risk of HCC by almost half in HBV chronic carriers, with moderate drinkers' risk reduced by almost 60% compared with those with no coffee-drinking habit. These results were consistent with findings from large-scale studies in Japan3 5 9 10 and Europe,4 8 in which daily coffee-drinking was found to protect against HCC in the general population and HBV carriers.2 14 Even at a much lower dosage, the level of protection was comparable.

While the findings are encouraging, the study was limited by the relatively small sample size and the case–control design, which might have introduced recall bias. The use of prevalence cases might also have introduced survivor effect. However, as HCC participants in the present sample had a longer median time from diagnosis of 31 months compared with reported median survival rates,18 19 any survivor effect might have underestimated rather than overestimated the protective effect of coffee. The lack of control on viral load, platelet count, alanine aminotransferase level and other possible factors for HCC is another limitation. Bearing these limitations in mind, the results from the present study suggest that moderate coffee consumption significantly reduced the risk of HCC in HBV carriers. Our converging evidence with previous studies calls for clinical trials to study more rigorously the causal relationship between coffee consumption and HCC risk. In itself, results from this study suggest that coffee drinking, being a simple, economical and easily modifiable lifestyle factor, may have important benefits for HBV carriers and their families even in moderate amounts for the large number of such individuals and their families in Hong Kong.

What is already known on this subject

Recent epidemiological studies reported a dose-dependent protective effect of coffee on HCC with risk reduction ranging from 30% to 80% in daily coffee drinkers compared with non-drinkers.

What this study adds

Even at a much lower dosage of occasional to moderate coffee consumption, the level of protection from HCC was comparable at 60%.

References

Footnotes

  • Funding This study was funded by the Centre for Research and Promotion of Women's Health at The Chinese University of Hong Kong, Hong Kong SAR.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Joint CUHK-NTEC Clinical Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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