ABSTRACT
Background & aims:
Coffee consumption has been linked to a reduced risk of liver disease, but large-scale prospective studies integrating imaging biomarkers, proteomics, and intake patterns remain limited. The effects of coffee type, additives, and metabolic modifiers are also unclear.
Methods:
We analyzed 354,957 UK Biobank participants without baseline cirrhosis or hepatocellular carcinoma. Coffee consumption, type (caffeinated/decaffeinated), and additives (sugar/sweeteners) were assessed by questionnaire. Incident cirrhosis, hepatocellular carcinoma, and liver-related mortality were ascertained through linked records. In a subcohort (n = 28,961) undergoing magnetic resonance imaging, hepatic fat (proton density fat fraction), iron, and fibroinflammation (iron-corrected T1) were evaluated. Proteomic profiling (n = 44,633) used Olink assays. Models were adjusted for demographic, behavioral, metabolic, and genetic covariates.
Results:
Over a median 13-year follow-up, higher coffee intake showed a graded reduction in liver outcomes, with ≥5 cups/day group having risk reductions of cirrhosis (hazard ratio, 0.68; 95% confidence interval, 0.58-0.79), hepatocellular carcinoma (hazard ratio, 0.53; 95% confidence interval, 0.34-0.83), and liver-related mortality (hazard ratio, 0.58; 95% confidence interval, 0.45-0.74). Protective associations were similar for caffeinated and decaffeinated coffee and persisted among those adding sugar or artificial sweeteners, although additive use correlated with modestly higher iron-corrected T1. Higher coffee intake corresponded to lower hepatic fat, iron, and fibroinflammation. Proteomic analysis revealed consistent patterns: higher levels of hepatocellular synthesis and complement proteins (transthyretin, selenoprotein P, complement factor H-related protein4/5) and lower levels of fibrogenic and macrophage-activation markers (microfibril-associated protein 4, colony stimulating factor 1 receptor, ectonucleotide pyrophosphatase/phosphodiesterase 2, transthyretin) with coffee drinking.
Conclusions:
Higher coffee intake was associated with favorable clinical, imaging, and proteomic indicators of liver health. These multidimensional findings support moderate unsweetened coffee as a simple strategy for liver disease prevention.
