A prospective study found that biological ageing-related plasma proteomics can improve chronic liver disease prediction, suggesting that protein-level information adds more predictive value than genetic risk alone for early risk stratification, for metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis.
Researchers obtained primary research data from UK Biobank, recruiting participants aged between 40-69 years between 2006 and 2010. 325,580 participants who had no missing data and liver disease at baseline were included.
Researchers assessed incident liver disease, MASLD, cirrhosis, liver cancer, and liver-specific mortality. Two measures were calculated at baseline biological age (estimated using Klemera-Doubal Method age) and phenotypic age (derived from nine blood biomarkers and lymphocyte percentage).
Biological age acceleration (BioAgeAccel) and PhenoAgeAccel were stratified into four categories: Group1 (< − 1 SD), Group2 (–1 SD to 0), Group3 (0 to + 1 SD), and Group4 (> + 1 SD).
Proteins associated with ageing acceleration, MASLD, and cirrhosis were identified using differential-expression analyses. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify disease-related protein modules.
Researchers found not only that accelerated biological ageing can be associated with the risk of chronic liver disease, but also that ageing acceleration can improve liver disease risk stratification.
Participants with liver disease (LD) had a higher average acceleration than those who didn’t (BioAgeAccel and PhenoAgeAccel were1.14 and 1.79 years higher than in participants without LD respectively).
Both BioAgeAccel and PhenoAgeAccel were independently linked to the risks of overall liver disease, MASLD, cirrhosis, liver cancer, and liver disease-related death. Stronger effects were found for PhenoAgeAccel on severe outcomes, especially cirrhosis, liver cancer, and liver-related mortality.
Researchers found 361 proteins were associated with MASLD and 936 proteins with cirrhosis, MASLD proteins were mainly involved in leukocyte migration, chemotaxis, and regulation of cell proliferation and cirrhosis with broader immune activation signatures.
Researchers concluded that biological ageing can be an important part of chronic liver disease risk, suggesting that ageing-proteomic profiling can be used to identify individuals at high risk before overt clinical progression. Further research in more diverse populations could confirm the findings’ broader applicability.
Reference:
Ding J et al. Biological ageing-related plasma proteomics improves chronic liver disease prediction: a prospective UK Biobank study. BMC Gastroenterol. 2026;DOI:10.1186/s12876-026-05369-1
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