Background: Increased serum tumor necrosis factor-alpha (TNF-alpha) concentrations are associated with disease progression in some cancers. Also, TNF-alpha is known as an important mediator of cancer cachexia. This study was conducted to investigate the relationship between serum TNF-alpha levels and disease and nutritional status in patients with hepatocellular carcinoma.
Methods: Thirty-one male cirrhotic patients with hepatocellular carcinoma (mean age: 65 +/- 2 years), 26 male cirrhotic patients without hepatocellular carcinoma (mean age: 59 +/- 3 years), and 25 male control subjects (mean age: 67 +/- 2 years) were included. Body fat mass was examined by bioelectrical impedance analysis. Serum TNF-alpha levels were measured by immunoassay. Hepatocellular carcinoma progression was staged by Okuda's classification.
Results: Serum TNF-alpha values in 31 patients with hepatocellular carcinoma and 26 patients with cirrhosis were significantly above those of controls (12.3 +/- 0.7 pg/mL vs. 11.3 +/- 1.2 pg/mL vs. 5.8 +/- 0.7 pg/mL; p < 0.01), but showed no differences between hepatocellular carcinoma and cirrhotic patients. When hepatocellular carcinoma patients were grouped according to Okuda's classification, the serum TNF-alpha levels significantly increased with disease progression (p < 0.05). Only in patients at stage III (n = 5), but not at stages I (n = 13) and II (n = 13), was the serum TNF-alpha levels greater than those in cirrhotic patients (p < 0.05). The serum albumin values and body fat mass in patients with hepatocellular carcinoma were both lower than in controls [(34 +/- 1 g/L vs. 42 +/- 1 g/L; p < 0.01); (15.9 +/- 1.2 kg vs. 18.9 +/- 0.8 kg; p < 0.05), respectively]. Further, both decreased significantly with disease progression by Okuda staging [(37 +/- 1 g/L vs. 32 +/- 2 g/L vs. 30 +/- 1 g/L; p < 0.01); (19.4 +/- 1.6 kg vs. 13.9 +/- 1.8 kg vs. 11.7 +/- 2.0 kg; p < 0.05); respectively]. Finally, a negative correlation was found between serum TNF-alpha and both fat mass (p = -0.40; p < 0.05) and serum albumin (p = -0.45; p < 0.05).
Conclusions: Our study demonstrated that serum TNF-alpha levels were increased in patients with hepatocellular carcinoma, and associated with disease severity and nutrition status. However, serum TNF-alpha should not be used as a marker to early diagnose hepatocelluar carcinoma in cirrhotic patients.