Aim: The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis.
Methods: Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data.
Results: The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP.
Conclusion: Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.