Moderate unsweetened coffee consumption could be a simple, scalable strategy for preventing liver disease.A recent study has shown an association between higher coffee intake and lower risks of cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality.
“[Our results show that] higher coffee consumption dose-dependently reduces cirrhosis, HCC, and liver-related mortality, supported by MRI biomarkers and a proteomic profile of attenuated fibrogenesis,” the investigators said.
Over a median follow-up of 13 years, coffee intake of ≥5 cups/day was associated with a graded reduction in liver outcomes, such as cirrhosis (hazard ratio [HR], 0.68; p for trend<0.001), HCC (HR, 0.53; p for trend<0.001), and liver-related mortality (HR, 0.58; p for trend<0.001) as opposed to no daily coffee intake.
The protective effect of coffee was evident even with lower intake (≥1–2 cups per day) compared with no consumption (HRs, 0.80, 0.76, and 0.69 for cirrhosis, HCC, and liver-related mortality, respectively). [Clin Gastroenterol Hepatol 2026:S1542-3565(26)00404-0]
According to the researchers, the protective associations were consistent for caffeinated and decaffeinated coffee.
MRI, proteomic subcohorts
Among individuals who underwent MRI (n=28,961), higher coffee consumption correlated with more favourable quantitative liver biomarkers. Those consuming ≥5 cups per day had significantly lower hepatic fat content (Proton Density Fat Fraction, –0.83 percent; p<0.001), lower odds of fibro-inflammation (cT1; odds ratio, 0.80), and significantly lower liver iron content (p for trend<0.001). This analysis also showed a correlation between sweetener use and higher cT1.
On proteomic profiling (n=44,633), coffee intake was associated with higher levels of hepatocellular synthesis (TTR, SELENOP) and complement proteins (CFHR4/5, SERPIND1, APCS) and lower levels of fibrogenic and macrophage-activation markers (MFAP4, CSF1R, ENPP2, THY1, NOTCH3).
“By leveraging the size and phenotypic depth … with detailed metabolic and genetic data, our study strengthens both biological and epidemiologic plausibility for a protective role of coffee against liver disease progression,” the researchers said.
A simple, scalable strategy
Coffee intake has been associated with a reduced risk of liver disease, but large-scale prospective studies integrating imaging biomarkers, proteomics, and intake patterns remain limited.
The investigators thus analysed data of 354,957 UK Biobank participants (mean age at baseline 57 years, 49.5 percent men) without baseline cirrhosis or HCC. Coffee consumption, type (caffeinated/decaffeinated), and additives (sugar/sweeteners) were assessed by questionnaire. Incident cirrhosis, HCC, and liver-related mortality were ascertained through linked records.
Approximately 46 percent of the participants reported daily coffee consumption of 1–2 cups, 21.1 percent reported 3–4 cups, and 11.5 percent reported ≥5 cups. About 15 percent of participants consumed decaffeinated coffee, and 3.4 percent reported using sugar or artificial sweeteners.
“Our study, extending UK Biobank follow-up through 2023 with a greater number of adjudicated outcomes than earlier analyses, provides the most comprehensive assessment to date of long-term coffee consumption and liver health,” the researchers said.
“Given coffee’s wide availability, safety, and affordability, promoting moderate unsweetened coffee consumption could represent a simple, scalable strategy for liver disease prevention,” they added.
The researchers acknowledged the need for future research that integrates dietary, genetic, and multi-omics data to ascertain causal mechanisms and identify subgroups that would benefit most from coffee consumption.