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.
- hepatocellular carcinoma
- liver disease
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Contributors The study was conceived by all authors; The search was performed by OK. The studies were reviewed and selected by RB and OK. The quality of evidence assessment was performed by OK. The risk of bias assessment was performed by JP and OK. The data were extracted and checked by OK and RB, respectively. The statistical analysis was performed by OK. The manuscript was drafted by OK and reviewed and amended by all authors. JP is guarantor.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
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