ORIGINAL ARTICLE   

Panminerva Medica 2017 December;59(4):283-9

DOI: 10.23736/S0031-0808.17.03353-5

Copyright © 2017 EDIZIONI MINERVA MEDICA

language: English

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

Gian P. CAVIGLIA ¹ ✉, Maria L. ABATE ¹, Silvia GAIA ², Elisa PETRINI ², Caterina BOSCO ¹, Antonella OLIVERO ¹, Chiara ROSSO ¹, Alessia CIANCIO ^{1, 2}, Rinaldo PELLICANO ², Giorgio M. SARACCO ^{1, 2}, Mario RIZZETTO ^{1, 2}, Antonina SMEDILE ^{1, 2}

¹ Department of Medical Sciences, University of Turin, Turin, Italy; ² Department of Gastroenterology and Hepatology, Città della Salute e della Scienza, Molinette Hospital, Turin, Italy

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.

KEY WORDS: Alpha-fetoproteins - Carcinoma, hepatocellular - MicroRNAs