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Keywords:

  • serum cytochrome c;
  • serum cytokeratin-18;
  • serum M30-CK18;
  • HCV ;
  • chronic hepatitis C;
  • sustained virological response

Abstract

Background & Aims

Cytochrome c (CYC) and M30-neoepitope of cytokeratin-18 (M30-CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30-CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC).

Methods

Seventy CHC patients were enrolled in this study. Forty five of them completed pegylated interferon plus ribavirin therapy. Histopathological evaluation of hepatic inflammatory activity and fibrosis, as well as blood liver function tests, was performed. Serum concentrations of M30-CK18 and CYC were measured by ELISA.

Results

Median serum concentration of M30-CK18 was higher in CHC patients [283 U/L] vs. control [113 U/L] (P = 0.0003) and was associated with inflammatory activity and liver fibrosis (P < 0.001). Serum M30-CK18 positively correlated with serum activity of ALT and GGT. CYC was not detected in sera of control group, whereas in CHC, 41.43% patients had detectable CYC in serum samples [0.60 ng/ml]. Detectable baseline serum CYC had been negatively associated with sustained virological response (SVR). In patients with detectable CYC, SVR rate was 20% vs. 60% in patients with undetectable CYC (P = 0.007).

Conclusions

Elevated serum M30-CK18, as an indicator of enhanced apoptosis of hepatocytes, parallels active hepatic inflammation and fibrosis but also biochemical activity in CHC; thus, it may serve as a comprehensive non-invasive marker of disease activity. On the other hand, detection of serum CYC at baseline may be negatively associated with treatment response to pegylated interferon plus ribavirin in CHC.