Evaluation of Interleukin-6, Interleukin-10 and Human Hepatocyte Growth Factor As Tumor Markers for Hepatocellular Carcinoma

Aim: Serum alpha-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC.

Method: A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects (n=29), chronic hepatitis B or C (n=50), non-HCC tumors (n=23) and HCC (n=26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects.

Results: The expression of IL-6 or IL-10 (> or =3 pg/ml), or high level of HGF (>1000 pg/ml) or AFP (>20 ng/ml) was observed in only 0-3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels (p<0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (<20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC (p<0.05). Patients with large (>5 cm) HCC more often had increased IL-6, IL-10 or AFP levels (p values all <0.05).

Conclusions: Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients.