| Title: | Fibro-inflammatory liver injury, not steatosis, predicts incident composite neuropsychiatric events and mortality in the UK Biobank |
| Journal: | Metabolism |
| Published: | 17 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42150669/ |
| DOI: | https://doi.org/10.1016/j.metabol.2026.156635 |
Publication 20010
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Abstract
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.</p>
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.</p>
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).</p>
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.</p>
17 Authors
- Tsubasa Tsutsumi
- Wen Hui Lim
- Darren Jun Hao Tan
- Jing Kai Tioh
- Damien Chua
- Hun Jee Choe
- Ryan Yanzhe Lim
- Mirudhula Gnanavelou
- Jordan Jun Yi Low
- Benjamin Y Q Tan
- Hirokazu Takahashi
- Weiting Huang
- Mamas A Mamas
- Anurug Mehta
- Mei Chin Lim
- Cheng Han Ng
- Mark Dinesh Muthiah
1 Application
| Application ID | Title |
|---|---|
| 99188 | Predictors of hepatic and extrahepatic outcomes in Non-alcoholic Fatty Liver Disease (NAFLD) and associated metabolic diseases |
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