BackgroundSeveral plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations.MethodsWe prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495006 men and women of the National Institutes of Health-AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided.ResultsWe found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,- f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b] pyridine (PhIP), were not associated with either outcome. ConclusionOur results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk.