Circulating histones as potential biomarkers of MASLD-MASH-HCC progression.

BACKGROUND

Reliable biomarkers are warranted to identify patients with metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), at risk for developing hepatocellular carcinoma (HCC).

RESEARCH AND

METHODS

We evaluated whether circulating histones can predict this risk. Plasma histones were measured using imaging flow cytometry in patients with MASLD (n = 25), MASH (n = 25), HCC (n = 40), and 30 healthy controls.

RESULTS

We detected (p < 0.05), compared to controls: 1) elevated levels of H2A, H3, H2A/H2B/H3/H4, macroH2A1.1, macroH2A1.2 in MASLD/MASH and HCC; 2) decreased levels of macroH2A1.2/H2B/H3/H4 in MASLD/MASH and increased in HCC; 3) reduced H4 levels discriminating between MASH and non-MASH. Machine-learning analysis showed that being diabetic/dyslipidemic, having decreased H2A (p = 0.002) and H4 (p = 0.0156) levels favor MASH.

CONCLUSIONS

Our data indicate plasma histones H2A and H4 as new biomarkers of liver disease progression. The identification of histone-based biomarkers using imaging flow cytometry could provide a rapid approach to discriminate between non-MASH and MASH, and to predict the risk of HCC development.