Plasma nitrites/nitrates in HCV infection and hepatocellular carcinoma

Nitric oxide (NO) is produced in response to inflammatory and mitogenic stimuli and may have a role in carcinogenesis. However, the role of NO in hepatitis C-associated hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the potential role of NO in HCC complicating hepatitis C virus (HCV) infection.

We measured plasma nitrites/nitrates as being representative for NO release in blood of patients with chronic hepatitis C without cirrhosis (n = 20), cirrhosis of different aetiologies (n = 30) including HCV, HCC (n = 22) and in healthy controls (n = 8), by an enzyme-linked immunosorbent assay.

Plasma NO levels in patients with chronic hepatitis C without cirrhosis (32.3+/-8.94 micromol/l) were not significantly different from those in healthy control subjects (35.5+/-15.12 micromol/l). Also, there were no statistical differences between plasma NO levels in patients on alpha-interferon (alpha-IFN) therapy (n = 10) (31.60+/-10.55 micromol/l) and in non-treated patients (n = 10) (33.00+/-7.51 micromol/l) within the group of chronic hepatitis C. Plasma NO levels in patients with cirrhosis (42.36+/-26.86 micromol/l) were significantly higher than those with chronic hepatitis C (P < 0.001). The cause of cirrhosis had no effect on plasma NO levels. Plasma NO levels in patients with HCC (49.40+/-49.11 micromol/l) were significantly higher than those with liver cirrhosis (P < 0.03). No significant correlation was found between plasma NO and serum ALT (alanine aminotransferase) levels. There were positive correlations between plasma NO levels and alkaline phosphatase (r = 0.528) (P = 0.0001), bilirubin (r = 0.244) (P = 0.039) and GGT (gamma glutamyltransferase) (r = 0.255) (P = 0.030).

The results of this study demonstrate that patients with chronic hepatitis C without cirrhosis have the same plasma NO levels as controls, and that alpha-IFN therapy had no effect on NO production in these patients. However, patients with HCC have elevated plasma NO levels compared with patients with cirrhosis. These data support the concept that NO is elevated in cirrhosis and HCC, but HCV infection does not appear to be responsible for the increase of NO in these patients. The severity of liver disease may be an important factor.