Human Epididymis Protein 4 Concentration is Not Associated with Liver Fibrosis and Cirrhosis in a Case Control Study

Background: Human epididymis protein 4 (HE4) is an emerging fibrotic biomarker which has been studied in chronic kidney disease cohorts. However, it is unclear if the serum level of HE4 may be altered in patients with liver fibrosis and cirrhosis.

Methods: we assessed serum HE4 concentrations in patients (n = 366) with chronic liver diseases (CLD) and compared to matched healthy controls (n = 366). Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) was also performed on all patients. Liver biopsy was performed on 34 of 366 subjects. Moreover, we analysed a subgroup of patients with confirmed cirrhosis to validate the correlation between HE4 and the severity of cirrhosis. Child-Pugh (CP) score was evaluated in this subgroup.

Results: No statistically significant differences were observed in the median HE4 level between patients with fibrosis and cirrhosis and controls (median: 56.2 vs. 55 pmol/L, p = .562). Neither were any significant differences found among different groups with Child-Pugh Classes A, B and C (median: 56.9, 58.3 and 52.1 pmol/L, respectively; p = .842). Correlation analysis did not show a significant correlation between HE4 and degree of liver fibrosis according to LSM values or histological assessment (r = 0.159, p = .239; r = 0.045, p = .788).

Conclusions: Serum HE4 level does not appear to be associated with fibrotic and cirrhotic liver, suggesting that HE4 may not serve as a valuable clinical biomarker for liver fibrosis and cirrhosis.