Abstract
Simple SummaryCirculating biomarkers for the early detection and prediction of hepatocellular carcinoma development are an unmet need. In the present study, we observed that serum values of three biomarkers (namely AFP, PIVKA-II and GPC-3) were significantly different between patients with cirrhosis and those with hepatocellular carcinoma; the best accuracy for the detection of tumors was achieved by a combination of AFP + PIVKA-II. However, PIVKA-II resulted as the only biomarker able to identify patients with cirrhosis at increased risk of hepatocellular carcinoma development. The measurement of PIVKA-II in patients with cirrhosis at risk of tumor development may be useful to tailor personalized surveillance strategies and thus to improve patients’ survival.International guidelines recommend the use of ultrasound as a surveillance tool for hepatocellular carcinoma (HCC) in patients with cirrhosis, while the role of serum biomarkers is still debated. We investigated serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA-II) and glypican-3 (GPC-3) diagnostic accuracy for HCC detection and prediction in patients with liver cirrhosis of viral etiology under surveillance. A total of 349 patients (200 cirrhosis and 149 HCC) were enrolled. The 200 patients with cirrhosis consisted of 114 patients still HCC-free after 36 months of follow-up and 86 patients that developed HCC after 13.8 (11.0–19.8) months. AFP, PIVKA-II and GPC-3 were measured in serum samples collected at tumor diagnosis in the 149 patients with HCC, and at the beginning of follow-up in the 200 patients with cirrhosis. The higher performance for HCC detection was observed for PIVKA-II (area under the curve (AUC) = 0.790), followed by AFP (AUC = 0.737) and GPC-3 (AUC = 0.637); the combination of AFP + PIVKA-II improved the diagnostic accuracy to AUC = 0.822. Serum PIVKA-II values, but not AFP and GPC-3, were significantly higher in the 86 cirrhotics that developed HCC compared with the 114 cirrhotics still HCC-free after 36 months of follow-up (p = 0.020). PIVKA-II ≥ 55 mAU/mL allowed to identify patients with cirrhosis at higher risk of HCC development (Log-rank test, p < 0.001; adjusted Hazard Ratio = 1.99, p = 0.001). In conclusion, the measurement of PIVKA-II in patients with cirrhosis may be useful to tailor personalized surveillance strategies.
Highlights
Liver cancer is the sixth most common cancer worldwide, with 841,000 new cases and 782,000 deaths per year [1]
Glypican-3 (GPC-3), protein induced by vitamin K absence or antagonist II (PIVKA-II)
Clinic Liver Cancer (BCLC), glypican-3 (GPC-3), interquartile range (IQR), protein induced by vitamin K absence or antagonist II (PIVKA-II)
Summary
Liver cancer is the sixth most common cancer worldwide, with 841,000 new cases and 782,000 deaths per year [1]. Hepatocellular carcinoma (HCC) constitutes more than 90% of primary liver cancers, and cirrhosis related to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection represents the key risk factor for the development of tumors [2]. The prognosis of HCC varies greatly according to tumor stage at the time of diagnosis; a timely detection is crucial in order to allow curative approaches and improve patients’ survival [3,4]. Surveillance programs for HCC detection in high risk populations are mainly based on abdominal ultrasonography (US), while the use of serum biomarkers is still a matter of debate [5,6,7]. US is a non-invasive and cost-effective method for screening purposes; the main limitation is represented by its sub-optimal sensitivity, especially for early-stage HCCs [8]. There is a need to adopt other non-invasive methods in association with US to improve the identification of potential neoplastic lesions
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