Evaluation of nitric oxide as a novel diagnostic marker for hepatocellular carcinoma

Abstract

Introduction: Liver cancer is the sixth most common cancer worldwide. HCC is the most common primary tumor of the liver. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for treatment of hepatobiliary cancers propose surveillance for the early
detection of HCC by liver ultrasonography every 3–6 months and evaluation of AFP. AFP >200 ng/ml is considered diagnostic for HCC, although fewer than half of patients of HCC may generate levels that are high, so that the specificity of AFP is close to 100% but the sensitivity is
45%. Nitrite/Nitrate is a stable end product of nitric oxide increase in patients with HCC. Aim: It was to evaluate nitric oxide as a novel diagnostic marker for hepatocellular carcinoma.

Methods: Eighty patients and 15 normal individuals enrolled in the study: Group (1) 15 normal individuals. Group (2) 30 patients with chronic liver disease without HCC. Group (3) 50 patients with HCC. History taking, clinical examination, (detection of liver masses, ascites, spleen size,
and grade of encepathalopathy), and Child-pugh scoring. Laboratory investigation: (AlT, AST, bilirubin, albumin, prothrombin, GGT, platelet count, AFP, nitric oxide, HBs-Ag, and HCV-Ab). Abdominal ultrasonography and spiral CT.

Results: The median level of nitric oxide was significantly higher in Group (3) (170 lmol/l) than in Group (2) (56 lmol/l) than in Group (1) (22 lmol/l), with a sensitivity of (68%) and specificity of (90%) at a cutoff level of 110 lmol/l and area under the curve of (0.810).While AFP, at a cutoff
level of 200 ng/ml had a sensitivity of (52%), specificity of (100%) and area under the curve (0.855). Indeed nitric oxide was high in 42% of AFP-negative HCC patients.
Conclusion: Nitric oxide is a novel diagnostic marker for hepatocellular carcinoma, the simultaneous determination of serum nitric oxide and AFP gave significant improvement in detection of HCC patients compared to that of AFP alone.