Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers

Arab J Gastroenterol. 2020 Jun;21(2):95-101. doi: 10.1016/j.ajg.2020.04.002. Epub 2020 May 18.

Abstract

Background and study aims: To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival.

Patients and methods: This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates.

Results: TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation.

Conclusion: Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.

Keywords: Cancer stem cells; Cytokeratin 19; Epithelial cell adhesion molecule (EpCAM); Hepatocellular carcinoma recurrence; Survival; Transient elastography.

MeSH terms

  • Biomarkers / analysis
  • Biomarkers / blood
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / therapy
  • Egypt / epidemiology
  • Elasticity Imaging Techniques / methods*
  • Epithelial Cell Adhesion Molecule / analysis*
  • Female
  • Humans
  • Keratin-19 / analysis*
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Cirrhosis / diagnosis
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplastic Stem Cells / pathology*
  • Outcome Assessment, Health Care / methods
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Survival Analysis

Substances

  • Biomarkers
  • Epithelial Cell Adhesion Molecule
  • Keratin-19