Risk of hepatocellular carcinoma in HBV cirrhotic patients assessed by the combination of miR-122, AFP and PIVKA-II.

Abstract

BACKGROUND:

Reliable biomarkers for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis are lacking. We evaluated the use of miR-122, alpha-fetoprotein (AFP) and protein induced by vitamin k absence/antagonist II (PIVKA-II) for HCC risk prediction in patients with HBV-related cirrhosis under surveillance.

METHODS:

We first analyzed a group of 63 patients with HBV-related liver cirrhosis of whom 33 had HCC. Then we performed a retrospective analysis on another group of 13 cirrhotic patients who developed HCC during surveillance, of whom serial serum samples were available (at time of HCC diagnosis [T0], 6-9 months [T-1] and 12-18 months [T-2] before HCC detection). Serum miR-122 levels were assessed by quantitative real time-PCR, whereas AFP and PIVKA-II were measured by fully automated chemiluminescent enzyme immunoassay.

RESULTS:

Serum levels of miR-122, AFP and PIVKA-II were different between patients with cirrhosis and those with HCC (P=0.024, P<0.001 and P<0.001, respectively). Areas under the curve (AUC) were 0.675 for miR-122, 0.791 for AFP and 0.846 for PIVKA-II, while their combination improved the discrimination power between cirrhosis and HCC (AUC=0.918). In the longitudinal study, we found a significant variation overtime for the biomarkers combination (P=0.011) but not for each single biomarker (miR-122, P=0.163; AFP, P=0.170; PIVKA-II, P=0.447). Combined miR-122+AFP+PIVKA-II adjusted Hazard Ratio for HCC development was 10.63, 95% confidence interval 1.87-60.28 (P<0.001).

CONCLUSIONS:

In HBV-related cirrhosis, the combination of miR-122, AFP and PIVKA-II enables the identification of patients at higher risk of HCC development that could benefit from closer monitoring.

• Authors: Gian P Caviglia, Maria L Abate, Silvia Gaia, Elisa Petrini, Caterina Bosco, Antonella Olivero, Chiara Rosso, Alessia Ciancio, Rinaldo Pellicano, Giorgio M Saracco, Mario Rizzetto, Antonina Smedile
• Journal: Panminerva medica (Panminerva Med) Vol. 59 Issue 4 Pg. 283-289 (Dec 2017) ISSN: 1827-1898 [Electronic] Italy
• PMID: 28650134 (Publication Type: Comparative Study, Journal Article)

Chemical References

• AFP protein, human
• Biomarkers
• MIRN122 microRNA, human
• MicroRNAs
• Protein Precursors
• alpha-Fetoproteins
• acarboxyprothrombin
• Prothrombin

Topics

• Area Under Curve
• Biomarkers (blood)
• Carcinoma, Hepatocellular (blood, diagnosis, virology)
• Cross-Sectional Studies
• Early Detection of Cancer (methods)
• Female
• Hepatitis B (blood, complications, diagnosis)
• Humans
• Liver Cirrhosis (blood, diagnosis, virology)
• Liver Neoplasms (blood, diagnosis, virology)
• Longitudinal Studies
• Male
• MicroRNAs (blood, genetics)
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Protein Precursors (blood)
• Prothrombin
• ROC Curve
• Reproducibility of Results
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Time Factors
• alpha-Fetoproteins (metabolism)