Fibro-inflammatory liver injury, not steatosis, predicts incident composite neuropsychiatric events and mortality in the UK Biobank.

BACKGROUND

Steatotic liver disease is associated with cardiovascular risk, yet the relevance of hepatic fibro-inflammatory activity to cerebral small vessel disease remains unclear. We investigated whether liver MRI phenotypes, iron-corrected T1 (cT1; fibro-inflammatory injury) and proton density fat fraction (PDFF; hepatic fat), and brain MRI white matter hyperintensity (WMH; cerebral small-vessel disease burden) predict incident composite neuropsychiatric events and mortality.

METHODS

This prospective study included 29,344 UK Biobank participants with liver and brain MRI. Participants were classified into four phenotypes based on liver imaging impairment (cT1 ≥ 800 ms) and high WMH burden (>80th percentile, age-adjusted). Cause-specific Cox models estimated risks for incident composite neuropsychiatric events (stroke, dementia, or late-life depression), liver events, and all-cause mortality, adjusting for prespecified covariates.

RESULTS

Over a median follow-up of 5.7 years, 530 participants developed neuropsychiatric events. Higher cT1 was associated with neuropsychiatric events (per 100 ms, hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04-1.65) and mortality (1.29, 1.04-1.60). Liver fat (PDFF) was not associated with composite neuropsychiatric events (1.00, 0.98-1.03) or mortality (1.00, 0.97-1.03). High WMH burden associated with neuropsychiatric events (1.26, 1.08-1.48) and mortality (1.17, 1.01-1.35). Participants with both elevated cT1 and high WMH had a higher risk of neuropsychiatric events (2.30, 1.00-5.29) and liver events (7.13, 3.32-15.33).

CONCLUSIONS

Fibro-inflammatory liver injury, rather than steatosis, was the primary liver MRI correlate of incident composite neuropsychiatric events and mortality. Combined liver-brain MRI phenotyping identified a high-risk subgroup, consistent with shared microvascular vulnerability.