Estimating the effects of Nordic diets on the risk of major adverse liver outcomes: a target trial emulation across two cohorts in Sweden.

BACKGROUND: Short-term trials show promising effects of a healthy Nordic Diet (HND) on liver fat and function, but whether these translate to the prevention of major adverse liver outcomes (MALO) remains unclear. OBJECTIVES: By emulating a (hypothetical) target trial, we estimated the effects of adhering to a HND or the Nordic Nutrition Recommendations 2023 (NNR23) on the 24-year risk of MALO and all-cause mortality in a middle-aged to elderly Swedish population. METHODS: Two population-based cohorts including n=64,406 males and females with repeated measurements in 1997, 2008/2009 and 2019 were used to emulate population-adapted versions of the diets. Under the assumptions of no unmeasured confounding, selection bias or measurement error, the parametric g-formula was used to estimate 24-year risks of MALO from each hypothetical intervention. A similar analysis was performed for the secondary outcome; all-cause mortality. RESULTS: The estimated 24-year risk of MALO for the HND was 0.53% (95% CI: 0.38, 0.73), for the NNR23 diet 0.70% (95% CI: 0.57, 0.90) and for no intervention 0.64% (95% CI: 0.56, 0.77). Estimated risk differences (RDs) of MALO for the HND versus no intervention and NNR23 versus no intervention were -0.11% (95% CI: -0.27, 0.07) and 0.06% (95% CI: -0.04, 0.15), respectively. Compared to NNR23, the estimated RD for the HND was -0.17% (95% CI: -0.38, 0.05). For all-cause mortality, the estimated risk difference for the HND versus no intervention was -2.67% (95% CI: -3.51, -1.85) and for NNR23 versus no intervention: -1.68% (95% CI: -2.75, -0.62). CONCLUSION: Under the strong assumptions of no unmeasured confounding, selection bias or measurement error, we estimated no risk reductions from a population-adapted HND or a NNR23 diet on the 24-year risk of MALO when compared to each other or no intervention. However, for all-cause mortality, we estimated meaningful risk reductions following the HND.