Activin A levels in metabolic dysfunction-associated steatotic liver disease associates with fibrosis and the PNPLA3 I148M variant

Abstract

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition worldwide. There is an urgent need to develop new biomarkers to assess disease severity and to define patients with a progressive phenotype. Activin A is a new promising biomarker with conflicting results about liver fibrosis. In this study we investigate levels of Activin A in patients with biopsy proven MASLD. We assess levels of Activin A in regard to fibrosis stage and genetic variant I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3).

Methods

Activin A levels were assessed in plasma samples from patients with biopsy-proven MASLD in a cross-sectional study. All patients were clinically evaluated and the PNPLA3 I148M genotype of the cohort was assessed.

Findings

41 patients were included and 27% of these had advanced fibrosis. In MASLD patients with advanced fibrosis, Activin A levels was higher (p < 0.001) and could classify advanced fibrosis with an AUROC for activin A of 0.836 (p < 0.001). Patients homozygous for PNPLA3 I148M G/G had higher levels of activin A than non-homozygotes (p = 0.027).

Conclusions

Circulating activin A levels were associated with advanced fibrosis and could be a potential blood biomarker for identifying advanced fibrosis in MASLD. Patients with the risk genotype PNPLA3 I148M G/G had higher levels of activin A proposing activin A as a contributor of the transition from simple steatosis to a fibrotic phenotype.

Keywords:

• NAFLD
• biomarkers
• NIT
• liver biopsy

Disclosure statement

No potential conflict of interest was reported by the authors.

CRediT authorship contribution statement

Conceptualization: CJ, ME. Data curation: CJ, PN, SK, ME. Formal analysis; CJ, MB, PN. Funding acquisition; PN, ME. Investigation: CJ, ME. Methodology; CJ, PN, ME. Project administration: all authors. Drafting of manuscript: CJ. Critical revision: all authors. All authors read and approved the final manuscript.

Additional information

Funding

This study is supported by ALF Grants, Region Östergötland, The Swedish Medical Society, Bengt Ihre Foundation, Ruth and Richard Julin Foundation, and Wallenberg Centre for Molecular Medicine, Linköping University.