Coffee consumption and liver cancer risk

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The more coffee consumed the greater the protection against hepatocellular cancer (HCC), including in pre-existing liver disease, according to a large observational study from the University of Southampton and the University of Edinburgh.

Drinking one cup more of caffeinated coffee a day was associated with a 20% reduction in the risk of developing HCC, two cups more with a 35% reduction, and up to five cups with a halving of the risk.

The protection was found to be the same for both existing coffee-drinkers and those who didn’t usually drink it, and the more coffee consumed the greater the effect – although there was little data available above five cups a day.

Decaffeinated coffee was also found to have a beneficial, though less marked, effect.

The research examined the data from 26 observational studies, involving more than 2.25m participants, to calculate the relative risks of developing HCC for drinking between one and five cups of caffeinated coffee a day.

Lead author Dr Oliver Kennedy, of the University of Southampton, said: “Coffee is widely believed to possess a range of health benefits, and these latest findings suggest it could have a significant effect on liver cancer risk.

“We’re not suggesting that everyone should start drinking five cups of coffee a day though. There needs to be more investigation into the potential harms of high coffee-caffeine intake, and there is evidence it should be avoided in certain groups such as pregnant women.

“Nevertheless, our findings are an important development given the increasing evidence of HCC globally and its poor prognosis.”

HCC is the second leading cause of cancer death globally because of its poor prognosis and high frequency, especially in China and Southeast Asia. It mostly develops in people who are already suffering from chronic liver disease.

It is estimated that, by 2030, the number of new cases annually will have risen by about 50% to more than 1.2m.

The compound molecules found in coffee possess antioxidant, anti-inflammatory, anti-carcinogenic and other beneficial properties which scientists believe may explain the lower rates of chronic liver disease and liver cancer experienced by coffee-drinkers.

About 2.25bn cups of coffee are consumed daily worldwide, and increased coffee consumption has already been shown to protect against serious non-cancer chronic liver disease (cirrhosis).

Professor Peter Hayes, of the University of Edinburgh, commented: “We have shown that coffee reduces cirrhosis and also liver cancer in a dose-dependent manner. Coffee has also been reported to reduce the risk of death from many other causes. Our research adds to the evidence that, in moderation, coffee can be a wonderful natural medicine.”

Kennedy added: “The next step now is for researchers to investigate the effectiveness, through randomised trials, of increased coffee consumption for those at risk of liver cancer.”

Objectives: To examine the association between coffee, including caffeinated and decaffeinated coffee, with hepatocellular carcinoma (HCC) and assess the influence of HCC aetiology and pre-existing liver disease.
Design: We performed a systematic review and meta-analysis. We calculated relative risks (RRs) of HCC according to caffeinated and decaffeinated coffee consumption using a random-effects dose–response meta-analysis. We tested for modification of the effect estimate by HCC aetiology and pre-existing liver disease. We judged the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.
Results: We found 18 cohorts, involving 2 272 642 participants and 2905 cases, and 8 case–control studies, involving 1825 cases and 4652 controls. An extra two cups per day of coffee was associated with a 35% reduction in the risk of HCC (RR 0.65, 95% CI 0.59 to 0.72). The inverse association was weaker for cohorts (RR 0.71, 95% CI 0.65 to 0.77), which were generally of higher quality than case–control studies (RR 0.53, 95% CI 0.41 to 0.69). There was evidence that the association was not significantly altered by stage of liver disease or the presence/absence of high alcohol consumption, high body mass index, type 2 diabetes mellitus, smoking, or hepatitis B and C viruses. An extra two cups of caffeinated and decaffeinated coffee (2 and 3 cohort studies, respectively) were associated with reductions of 27% (RR 0.73, 95% CI 0.63 to 0.85) and 14% (RR 0.86, 95% CI 0.74 to 1.00) in the risk of HCC. However, due to a lack of randomised controlled trials, potential publication bias and there being no accepted definition of coffee, the quality of evidence under the GRADE criteria was ‘very low’.
Conclusions: Increased consumption of caffeinated coffee and, to a lesser extent, decaffeinated coffee are associated with reduced risk of HCC, including in pre-existing liver disease. These findings are important given the increasing incidence of HCC globally and its poor prognosis.

Oliver John Kennedy, Paul Roderick, Ryan Buchanan, Jonathan Andrew Fallowfield, Peter Clive Hayes, Julie Parkes

University of Southampton material BMJ Open abstract

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