Rising plasma nociceptin level during development of HCC: a case report.

AIM: Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC), relatively few reports are available on HCC in primary biliary cirrhosis. High plasma nociceptin (N/OFQ) level has been shown in Wilson disease and in patients with acute and chronic pain. METHODS: We report a follow-up case of HCC, which developed in a patient with primary biliary cirrhosis. The tumor appeared 18 years after the diagnosis of PBC and led to death within two years. Alfa fetoprotein and serum nociceptin levels were monitored before and during the development of HCC. Nociceptin content was also measured in the tumor tissue. RESULTS: The importance and the curiosity of the presented case was the novel finding of the progressive elevation of plasma nociceptin level up to 17-fold (172 pg/mL) above the baseline (9.2+/-1.8 pg/mL), parallel with the elevation of alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development. Nociceptin content was more than 15-fold higher in the neoplastic tissue (0.16 pg/mg) than that in the tumor-free liver tissue samples (0.01 pg/mg) taken during the autopsy. CONCLUSION: Results are in concordance with our previous observation that a very high plasma nociceptin level may be considered as an indicator for hepatocellular carcinoma.

[Peripheral nociceptin levels in Wilson disease]. / Perifériás nociceptin szint Wilson-kórban.

Plasma level of nociceptin, the endogenous agonists of orphaninFQ/OP4 receptor was found to be significantly elevated in Wilson's disease patients (14.87 +/- 2.44 pg/ml +/- SD, p < 0.001, n = 21) compared to age-matched healthy controls (9.18 +/- 1.63 pg/ml +/- SD, n = 25). Wilson's disease is an autosomal recessive disorder caused by mutation of the gene ATP7B leading to toxic copper accumulation mainly in the liver and brain and in other organs such as, 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 in Wilson's disease patients. It is suggested that significantly elevated plasma nociceptin level is due to the inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N, endopeptidase 24.15) by the toxic copper levels, as it is known that changing the central Zn atom to Cu results in an approximately 50% inhibition in the activity of these enzymes. The high plasma nociceptin level in Wilson's disease patients may induce significant impairment in nociceptinerg neurotransmission.