Serum C7 levels predict liver-related events in metabolic fatty liver disease, study finds

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant global health risk, with liver fibrosis and related events (LREs) such as hepatocellular carcinoma becoming important clinical indicators. Current methods to assess fibrosis severity and predict future LREs are limited by invasiveness, cost, and accuracy.

To address this, researchers at Shinshu University, Japan, led by Dr. Takefumi Kimura, investigated serum complement C7 as a potential biomarker for fibrosis and LREs in MASLD. The study, published in JHEP Reports, evaluated serum C7 levels across three cohorts: 430 biopsy-confirmed MASLD patients, 120 using vibration-controlled transient elastography (VCTE), and 4,486 UK Biobank participants.

The researchers found that elevated serum C7 levels (threshold 140 μg/mL) were independently associated with higher LRE incidence (hazard ratio 4.54). C7 expression was localized to activated hepatic stellate cells in fibrotic liver regions, and single-nucleus RNA sequencing identified hepatic stellate cells as an important source of C7.

In vitro experiments showed that C7 knockdown reduced expression of extracellular matrix-related genes. The study's multi-omics approach, incorporating transcriptomics, proteomics, spatial, and single-cell analyses, suggests serum C7 could provide valuable information on fibrosis burden and clinically relevant disease progression.

However, causality and generalizability require further investigation through prospective studies and in vivo experiments. Serum C7 holds potential as a noninvasive biomarker for stratifying MASLD fibrosis severity and predicting clinical outcomes.