Role of Follistatin and C- Reactive Protein in Nafld: A Comprehensive Review

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease globally and is closely linked to obesity, insulin resistance and metabolic dysfunction. In recent years, there has been growing interest in circulating biomarkers that can identify individuals at risk of NAFLD or progressive disease. Among these, C-reactive protein (CRP) is a well-established inflammatory marker, whereas follistatin, a multifunctional hepatokine, has emerged as a potential modulator of metabolic and hepatic processes.

Aim: This review synthesises human evidence from 2015–2025 examining the roles of CRP and follistatin in NAFLD, integrating epidemiological, clinical and mechanistic findings to evaluate their potential as biomarkers in overweight individuals.

Methods: A narrative review approach was employed, focusing on peer-reviewed human studies published between 2015 and 2025 that assessed CRP, follistatin or related metabolic and inflammatory markers in NAFLD. Mechanistic insights from translational and hepatokine research were included to contextualise clinical findings.

Results: CRP is consistently elevated in individuals with NAFLD and independently predicts incident disease, including in lean and non-obese populations. Higher CRP also correlates with hepatic steatosis and fibrosis, supporting its utility as a clinically accessible marker of metabolic and inflammatory risk. In contrast, evidence for circulating follistatin is more variable. Although serum FST shows limited discriminatory value between NAFLD phenotypes, mechanistic studies demonstrate its important roles in adipose–liver cross-talk, insulin resistance and lipid handling. Hepatic follistatin expression may counteract steatosis, whereas elevated systemic FST may exacerbate metabolic dysfunction, highlighting its dual context-dependent actions.

Conclusion: CRP presently offers greater clinical utility for NAFLD risk assessment, particularly in overweight individuals where metabolic risk is frequently underestimated. Follistatin, despite its biological relevance, requires further large-scale human validation before clinical application. Integration of inflammatory biomarkers, hepatokines and metabolic indices may ultimately enhance early detection and phenotypic stratification in NAFLD.