High plasma concentrations of nitrite/nitrate in patients with hepatocellular carcinoma

Abstract

Objectives: Nitric oxide (NO) is considered to play a central role in macrophage or Kupffer cell-induced tumor cytotoxicity. Hepatocytes also produce NO in response to several inflammatory stimuli. Thus, there is a possibility that NO production by hepatic tissue is accelerated in patients with hepatocellular carcinoma (HCC). We, therefore, measured plasma nitrite/nitrate levels as an index of in vivo NO production in patients with HCC.

Methods: Plasma nitrite/nitrate levels were measured using Griess reaction in 95 patients with chronic hepatitis (CH) and compensated liver cirrhosis (LC) with (n = 48) or without HCC (n = 47), as well as 45 healthy control subjects. Possible factors related to nitrite/nitrate levels were evaluated for each subject.

Results: Plasma nitrite/nitrate levels in patients with HCC based on CH (mean +/- SD, 71.7 +/- 23.1 microM) and LC (52.4 +/- 20.2 microM) were significantly higher than those without HCC (CH, 31.1 +/- 15.0 microM; LC, 34.6 +/- 16.1 microM) (p < 0.01). Plasma nitrite/nitrate levels in patients with HCC based on CH were significantly higher than those in patients with HCC based on LC (p < 0.05). Simple regression analysis showed that plasma nitrite/nitrate levels significantly correlated with both tumor surface area (r = 0.577, p = 0.001) and tumor volume (r = 0.532, p = 0.003).

Conclusion: Patients with HCC have elevated plasma nitrite/nitrate levels correlating to tumor volume as well as tumor surface area.