Serum Zonulin in HBV-Associated Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Dis Markers. 2019 Aug 14:2019:5945721. doi: 10.1155/2019/5945721. eCollection 2019.


Background: The gut microbiota is involved in the occurrence and development of chronic liver diseases. Zonulin is considered a marker of intestinal permeability. The purpose of this study was to assess zonulin levels in patients with chronic hepatitis B (CHB), HBV-associated liver cirrhosis (LC), and HBV-associated hepatocellular carcinoma (HCC).

Materials and methods: The study population consisted of 90 HBV-associated HCC patients, 90 HBV-associated LC patients, 90 CHB patients, and 90 healthy subjects. Serum levels of zonulin and AFP were determined. The diagnostic accuracy of each marker was evaluated using receiver operating characteristic (ROC) curve analysis (AUC).

Results: Serum zonulin levels were significantly higher in patients with HCC than in patients with LC or CHB or healthy subjects (p < 0.001). Moreover, the zonulin levels were increased in the advanced stage of LC and HCC. ROC curve analysis revealed that serum zonulin could be used to differentiate CHB from cirrhosis. In addition, the combination of zonulin and AFP exhibited a significantly larger AUC compared with zonulin or AFP alone.

Conclusions: Serum zonulin levels were significantly increased both in LC and in HCC and correlated with the advanced stage of LC and HCC. Moreover, the combination of zonulin and AFP confers significant benefit to diagnostic accuracy in differentiating LC from HCC.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Female
  • Haptoglobins
  • Hepatitis B, Chronic / blood*
  • Humans
  • Liver Cirrhosis / blood*
  • Liver Neoplasms / blood*
  • Male
  • Middle Aged
  • Protein Precursors / blood*
  • alpha-Fetoproteins / analysis


  • AFP protein, human
  • Biomarkers, Tumor
  • Haptoglobins
  • Protein Precursors
  • alpha-Fetoproteins
  • zonulin