Higher coffee consumption was associated with lower risks of cirrhosis, liver cancer, and liver-related death in a large study of more than 354,000 patients. Magnetic resonance imaging and blood protein analyses also pointed to possible biologic mechanisms behind the association.
The analysis, published in Clinical Gastroenterology and Hepatology, included 354,957 UK Biobank participants without cirrhosis or hepatocellular carcinoma at enrollment who were followed for a median of 13 years. The researchers assessed self-reported coffee consumption, including coffee type and whether participants added sugar or artificial sweeteners. They then examined how those habits were associated with new cases of liver disease, magnetic resonance imaging (MRI) measures of liver health in a subgroup of 28,961 patients, and blood protein profiles in 44,633 patients. The analyses accounted for factors including age, sex, smoking, alcohol use, metabolic conditions, socioeconomic status, body mass index, and PNPLA3 genotype.
Compared with patients who did not drink coffee, those who drank at least five cups a day were 32% less likely to develop cirrhosis, 47% less likely to develop hepatocellular carcinoma, and 42% less likely to die from liver disease. The association followed a dose-response pattern, with lower risks seen starting at one to two cups a day. The findings were similar for caffeinated and decaffeinated coffee.
The investigators also examined whether adding sugar or artificial sweeteners changed the association between coffee and liver health. Overall, patients who added sweeteners had similar reductions in the risk of cirrhosis, hepatocellular carcinoma, and liver-related death as those who drank unsweetened coffee. However, they had 1.36 times the odds of elevated iron-corrected T1, an MRI marker of liver inflammation and fibrosis, compared with patients who did not add sweeteners.
MRI findings also suggested that higher coffee intake was associated with better liver health before liver disease became clinically apparent. Patients who drank at least five cups a day had less liver fat, lower liver iron levels, and lower odds of liver fibroinflammation than non-coffee drinkers. The findings were similar for caffeinated and decaffeinated coffee, suggesting that components other than caffeine may play a role.
Proteomic analyses identified 74 proteins associated with both coffee intake and cirrhosis risk, suggesting biologic pathways related to liver function, inflammation, fibrosis, and immune regulation that may help explain coffee's observed associations with better liver health.
The authors noted several limitations, including self-reported coffee intake, the possibility of unmeasured confounding and reverse causation, a healthier MRI subgroup, and the predominantly European ancestry of the study population, which may limit the generalizability of the findings. They also said the blood protein findings require experimental studies to confirm the underlying biologic mechanisms.
“Higher coffee intake was associated with lower risks of cirrhosis, HCC, and liver-related mortality, as well as favorable MRI-based and proteomic profiles,” the authors concluded. They added that the combined clinical, imaging, and molecular findings support coffee as “a simple, scalable strategy for liver disease prevention.”
The study received no external funding. Ju Dong Yang, MD, reported consulting relationships with several companies; the remaining authors reported no relevant conflicts.
Expert Insight
GI & Hepatology News invited study author Hyunseok Kim, MD, MPH, PhD, of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, to comment on the implications of this work.
Why does this study matter?
Dr. Kim: Coffee has long been associated with better liver health, but most previous studies focused only on clinical outcomes such as cirrhosis or liver cancer. Our study is unique because it integrates clinical outcomes with advanced MRI biomarkers and large-scale plasma proteomics in more than 350,000 UK Biobank participants. By combining these complementary approaches, we were able to show not only that coffee consumption is associated with lower risks of cirrhosis, hepatocellular carcinoma, and liver-related mortality, but also that it is linked to less liver fat, less fibroinflammation on MRI, and favorable biological pathways involved in fibrosis and inflammation. This provides stronger biological evidence supporting coffee as a simple lifestyle factor that may promote liver health.
When you had all the data in front of you, was there a finding that surprised you?
Dr. Kim: Several findings stood out. First, we observed remarkably consistent associations across clinical outcomes, imaging biomarkers, and proteomic signatures, all pointing in the same direction. Second, both caffeinated and decaffeinated coffee showed similar associations, suggesting that compounds other than caffeine likely contribute to the liver benefits. Finally, we were intrigued that coffee drinkers had lower levels of proteins involved in fibrosis, macrophage activation, and extracellular matrix remodeling, while proteins reflecting healthier liver synthetic function were higher. These findings offer new mechanistic clues that go beyond the epidemiologic associations reported previously.
How might the findings influence clinical practice for gastroenterologists and hepatologists?
Dr. Kim: This study should not be interpreted as evidence that coffee is a treatment for chronic liver disease. However, for most patients without contraindications, moderate coffee consumption appears to be a safe, inexpensive, and potentially beneficial lifestyle habit that can complement other evidence-based interventions such as weight loss, alcohol abstinence, and management of metabolic risk factors. I hope these findings will give clinicians greater confidence when discussing dietary habits with patients and encourage further research into the biological mechanisms underlying coffee's protective effects.
Is there anything else you'd like to say about this work?
Dr. Kim: One of the strengths of this study is its multidimensional design. Rather than relying solely on clinical events, we incorporated MRI-derived imaging biomarkers and high-throughput proteomics to better understand the biological pathways associated with coffee consumption. This approach provides a more comprehensive picture of liver health and may help identify new therapeutic targets for preventing fibrosis and liver disease progression. While our findings are observational and do not prove causality, they provide a strong rationale for future mechanistic studies and, potentially, clinical trials evaluating dietary interventions in liver disease.