Liver Fibrosis Tied to Cognitive Decline, Brain Shrinkage


Advanced liver fibrosis may contribute to cognitive decline and brain atrophy, mediated in part by elevated C-reactive protein (CRP), a marker of systemic inflammation.


  • Cross-sectional associations between liver fibrosis (measured by Fib-4 score), cognitive function, and regional grey matter volume (GMV), adjusting for multiple covariates, were examined.

  • A post-hoc preliminary analysis investigated CRP’s mediating effect.

  • Data from up to 447,626 UK Biobank participants aged 37 and older were analyzed.


  • Significant associations were observed between liver fibrosis and cognitive performance across different metrics including reasoning, memory, executive function, and processing speed.

  • Liver fibrosis correlated significantly with reduced regional GMV, primarily in the hippocampus, thalamus, ventral striatum, parahippocampal gyrus, brain stem, and cerebellum.

  • CRP levels were significantly higher in adults with advanced liver fibrosis, indicating elevated systemic inflammation.

  • Serum CRP significantly mediated the effect of liver fibrosis on most cognitive measures and regional GMVs in the hippocampus and brain stem.


“Early surveillance and prevention of liver diseases may reduce cognitive decline and brain GMV loss,” the authors write in a press release.


The study was led by Rongtao Jiang, PhD, with Yale School of Medicine, New Haven, Connecticut. It was published online June 23 in eBioMedicine. The study was funded by the National Science Foundation and National Institutes of Health.


The cross-sectional study design in adults of mostly European ancestry, and reliance on the Fib-4 score, which is less accurate than liver biopsy and has low sensitivity in assessing hepatic fibrosis.


The authors have reported no relevant financial relationships.

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