Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma.

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.

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.

Efficacy of interferon treatment (IFN) in elderly patients with chronic hepatitis C.

The aim of this study was to evaluate the efficacy and tolerability of interferon treatment in aged patients with chronic hepatitis C. One hundred and fifty-four patients with chronic hepatitis C, consecutively treated with a-interferon (a-IFN), were retrospectively subdivided into two groups according to age =60 or <60 years. The two groups were compared in terms of biochemical and histological activity of the disease, HCV genotype, total dose of IFN received, incidence of side effects and rate of response to treatment. Statistical analysis was performed by Student's t test, chi-square test and Fisher's exact test. Aged patients had a higher prevalence of HCV genotype 1b and cirrhosis and received a lower dose of the drug. No differences were found in other epidemiological-clinical characteristics before treatment. The rate of sustained response and long-term response to therapy was similar in the two groups of patients (18% and 8% in the aged and 20% and 13% in the younger respectively). There was a trend of more frequent major side effects in aged patients (p=0.07). Treatment of chronic hepatitis C with a-IFN had the same efficacy in the two groups observed. In aged patients with chronic hepatitis C treatment with the more effective pegylated IFN should be taken into consideration, especially when association with ribavirin is at high risk of adverse events.

Serum thrombopoietin in chronic liver disease: relation to severity of the disease and spleen size.

BACKGROUND/AIMS: Thrombopoietin is a thrombopoietic factor mainly synthesized in the liver. Its production is regulated by the mass of megakaryocytes and platelets. Impaired production of thrombopoietin may be responsible for thrombocytopenia in chronic liver disease. METHODOLOGY: We studied thrombopoietin serum concentration in 68 patients with chronic liver disease of various degrees (39 with thrombocytopenia), in 5 patients with thrombocytopenia due to hematological disease, and in 27 healthy controls. RESULTS: Thrombopoietin concentration was higher in patients with liver disease than in controls. Patients with hematological disease had much higher thrombopoietin concentration than patients with liver disease. Among patients with liver disease and thrombocytopenia, thrombopoietin concentration was higher in cirrhosis than in chronic hepatitis. A negative correlation was found between platelet counts and spleen size and between thrombopoietin concentration and spleen size. No correlation was found between thrombopoietin concentration and liver disease severity. CONCLUSIONS: Patients with liver disease and thrombocytopenia have serum thrombopoietin concentration higher than normal controls. It seems therefore that the liver, even seriously diseased, maintains the ability to produce thrombopoietin. In the liver patients the number of circulating platelets and the serum levels of thrombopoietin are inversely correlated with the size of the spleen suggesting that thrombopoietin, although normally produced, might be turned over in platelets sequestrated in the spleen.