Serum FGF21 and RBP4 levels in patients with chronic hepatitis C

Scand J Gastroenterol. 2012 Sep;47(8-9):1037-47. doi: 10.3109/00365521.2012.694901. Epub 2012 Jun 7.


Introduction: Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions.

Aims and methods: Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers.

Results: FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (β = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (β = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02).

Conclusions: Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Biomarkers / blood
  • Body Mass Index
  • Case-Control Studies
  • Fatty Liver / blood*
  • Fatty Liver / complications
  • Fatty Liver / pathology*
  • Female
  • Fibroblast Growth Factors / blood*
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Insulin Resistance
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Statistics, Nonparametric


  • Biomarkers
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Alanine Transaminase