Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma.

AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain, and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0+/-2.7 pg/mL, n=26), primary biliary cirrhosis (12.1+/-3.2 pg/mL, n=21) and liver cirrhosis (12.8+/-4.0 pg/mL, n=15) compared to the healthy controls (9.2+/-1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9+/-14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9+/-14.9 pg/mL, n=12) and without (107.7+/-14.5 pg/mL, n=6). CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.

Elevated plasma nociceptin level in patients with Wilson disease.

Plasma level of nociceptin, the endogenous agonist of orphanin FQ/ORL1 receptor was found to be significantly elevated in Wilson disease patients (13.98+/-2.44pg/ml, p<0.001, n=20) compared to age-matched healthy controls (9.18+/-1.63pg/ml, n=25). Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutation of the gene ATP7B leading to toxic copper accumulation in the liver and other organs such as brain, kidney and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found. It is suggested that elevated plasma nociceptin level found in Wilson disease patients is due to inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N (APN) and endopeptidase 24.15) by the toxic copper deposits in liver and/or brain.