Inverse Association of Coffee with Liver Cancer Development: An Updated Systematic Review and Meta-analysis

Coffee consumption has been suggested to reduce the risk for hepatocellular carcinoma (HCC). While several studies report inverse correlation with coffee drinking, others have suggested more than 2 cups of coffee every day decrease the risk of liver cancer or HCC. However, controversy exists about the exact dose that would provide protective benefit. Therefore, we aimed to carry out a systematic review and meta-analysis of all studies that investigated the association of coffee consumption and risk of HCC and/or liver cancer. Our outcomes were the evaluation of the association of coffee with HCC or liver cancer development along with the amount of coffee needed to prevent HCC or liver cancer.

We performed a PubMed/MEDLINE/EMBASE/Ovid/Google Scholar search of original articles published in English from 1996 to June 2019, on case-control or cohort or prospective studies that associated coffee with liver cancer or HCC. We calculated the relative risk (RR) of the two conditions for coffee drinking and then stratified this into increments of one cup of coffee per day. Twenty studies were identified. The analysis was performed using random effects models from the methods of DerSimonian and Laird with inverse variance weighting. The Cochrane Q and the I 2 statistics were calculated to assess heterogeneity between studies. A p<0.10 value for chi-square test and I 2 <20% were interpreted as low-level heterogeneity. Probability of publication bias was assessed using funnel plots and with the Egger's test.

The overall RR was 0.69 (95%CI 0.56-0.85; p<0.001) with significant heterogeneity between the studies. We performed subgroup analysis over the increments of 1 cup of coffee. Higher doses of coffee consumption were associated with a significant decrease in the risk of developing HCC or liver cancer. The funnel plot did not show significant publication bias.

Our systematic review and meta-analysis suggests that drinking coffee provides benefits with a reduction in the risk of HCC or liver cancer. Higher doses of coffee have higher benefits in terms of risk reduction. However, further biological and epidemiological studies are required to determine the exact mechanism and to study specific subgroups such as viral hepatitis B or C related HCC.