Abstract and Introduction
Background: Epidemiological data suggest that coffee has a dose-dependent protective effect on liver-related mortality.
Aim: To estimate the potential impact of increased per capita coffee consumption on global liver-related mortality.
Methods: Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver-related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/day (RR 0.54, 95% CI 0.42–0.69) and ≥4 cups/day (RR 0.29, 95% CI 0.17–0.50), adjusted for confounders and tested model assumptions using sensitivity analyses.
Results: Worldwide, there were an estimated 1,240,201 (95% CI 118 4300–1 354 410) adult liver-related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/100 000 population/year (all ages, both genders; IQR 11–21 deaths per 100 000). If all countries with per capita coffee intake ≤2 cups/day increased to >2 cups/day, the predicted total number of liver-related deaths would have been 630 947 in 2016 (95% CI 629 693–631 861) with 452 861 (95% CI 451 948–454 116) deaths averted (PPR 7.8 liver-related deaths/100 000/year). If per capita consumption was ≥ 4 cups/day, the predicted number of liver-related deaths in 2016 would have been 360 523 (95% CI 359 825–361 992) with 723 287 (95% CI 721 817–723 984) deaths averted (PPR 12.1 liver-related deaths/100 000/year).
Conclusion: Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver-related deaths annually if the impact of coffee on liver-related mortality is confirmed in clinical trials.
Liver disease is a major cause of morbidity and mortality globally. Worldwide, cirrhosis is estimated to be the cause of more than a million deaths annually, equating to more than 2% of all deaths. Moreover, hepatocellular carcinoma (HCC) due to liver disease is the third most common cause of cancer deaths worldwide, accounting for 745 000 deaths annually. There are numerous efforts to reduce this burden of disease occurring at both national and international levels, including vaccination and treatment strategies for hepatitis B and C. However, additional simple, cost-effective interventions are required to reduce the burden of liver disease-related mortality. Coffee is one such intervention that may have a potential role in this area.
For decades, it has been recognised that coffee intake offers some degree of protection against liver disease. The initial reports described an association between coffee intake and improvements in liver function tests.[5–8] Over more recent years, there have been a growing number of publications reporting that coffee intake not only improves liver biochemistry, but also slows progression to cirrhosis[9–13] and is associated with a reduced risk of death from liver disease.[14–18] The reported magnitude of the protection that coffee offers from liver death in cohort studies is impressive, though the impact on hepatitis B-related mortality is less certain. In one of the largest high quality prospective cohort studies to date, Setiawan and colleagues demonstrated a 46% reduction in death from liver cirrhosis for people assessed at study entry as drinking 2–3 cups/day; and a 71% reduction in death from cirrhosis in those consuming 4 or more cups daily, after adjusting for key confounders including age, BMI, diabetes, gender, race, education level and alcohol intake. The data were drawn from the US Multiethnic Cohort Study, a mixed-race cohort of 162 022 men and women from Hawaii and California, USA (25% Caucasian, 16% African American, 30% Asian, 7% Native Islander and 22% Hispanic) with and without chronic liver disease of diverse aetiologies, in whom HCC had been excluded at baseline. Importantly, the risk ratios in the Setiawan paper were derived from a prospective cohort study where baseline coffee consumption (exposure of interest) was recorded prior to liver-related mortality (outcome of interest), which minimises recall bias and allows for lag time analysis that reduces but does not remove the possibility of reverse causation due to lower coffee consumption in those with more severe liver disease. Similarly, the Singapore Chinese Health Study prospective cohort also revealed a similar reduction of 66% in liver-related mortality with increased coffee intake to two or more cups per day, however there was no observed impact on liver-related mortality for people with chronic hepatitis B. Importantly, published data have shown that reductions in liver-related mortality, liver cirrhosis and liver cancer are reported in Eastern and Western populations[14,19] supporting the suitability of coffee as a potential global intervention. While preliminary studies in animal models support the protective mechanism of coffee on liver fibrogenesis and liver damage,[11,20,21] the exact mechanism by which coffee attenuates fibrosis progression remains unclear.
Coffee ticks many of the boxes when it comes to potential interventions that may play a role in reduction in liver disease mortality at a global level. It is widely available, generally affordable and is associated with minimal side effects. The potential global health impact of coffee intake being advocated as a liver health therapy has not previously been explored and mathematical modelling is one way of exploring the potential impact of novel population-level interventions. The aim of this study was to estimate the potential reduction in liver disease-associated mortality with increased coffee consumption worldwide, using mathematical modelling and published estimates of relative risk reduction in liver-related mortality applied to the Global Burden of Disease 2016 dataset.
Aliment Pharmacol Ther. 2020;52(7):1195-1203. © 2020 Blackwell Publishing