Serum levels of soluble Fas, soluble tumor necrosis factor-receptor II, interleukin-2 receptor and interleukin-8 as early predictors of hepatocellular carcinoma in Egyptian patients with hepatitis C virus genotype-4

Abstract

Background: Liver disease progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) is associated with an imbalance between T-helper 1 and T-helper 2 cytokines. Evaluation of cytokines as possible candidate biomarkers for prediction of HCC was performed using soluble Fas(sFas), soluble tumor necrosis factor receptor-II (sTNFR-II), interleukin-2 receptor (IL-2R) and interleukin-8 (IL-8).

Results: The following patients were recruited: 79 with HCV infection, 30 with HCC, 32 with chronic liver disease associated with elevated liver enzyme levels (with or without cirrhosis) in addition to 17 with chronic HCV with persistent normal alanine aminotransferase levels (PNALT). Nine normal persons negative either for HCV or for hepatitis B virus were included as a control group. All persons were tested for sFas, sTNFR-II, IL-2R and IL-8 in their serum by quantitative ELISA. HCC patients had higher levels of liver enzymes but lower log-HCV titer when compared to the other groups. HCC patients had also significantly higher levels of sFas, sTNFR-II and IL-2R and significantly lower levels of IL-8 when compared to the other groups. Exclusion of HCC among patients having PNALT could be predicted with 90 % sensitivity and 70.6 % specificity when sTNFR-II is [greater than or equal to] 389 pg/ml or IL-8 is < 290 pg/ml.

Conclusions: Serum TNFR-II, IL-2Ralpha and IL-8, may be used as combined markers in HCV-infected cases for patients at high risk of developing HCC; further studies, however, are mandatory to check these findings before their application at the population level.

Figure 1

Scatter diagram of the distribution of log-HCV titer results among the different study groups. PNALT: Chronic hepatitis C with persistent normal alanine aminotrasferase; CLD: Chronic liver disease; HCC: hepatocellular carcinoma.

Figure 2

Scatter diagram representing the distribution values of sFas in the different study groups. NC: normal controls; PNALT: Chronic hepatitis C with persistent normal alanine aminotrasferase; CLD: Chronic liver disease; HCC: hepatocellular carcinoma.

Figure 3

Scatter diagram representing the distribution values of sTNFR-II in the different study groups. NC: normal controls; PNALT: Chronic hepatitis C with persistent normal alanine aminotrasferase; CLD: Chronic liver disease; HCC: hepatocellular carcinoma.

Figure 4

Scatter diagram representing the distribution values of sIL-2Rα in the different study groups. NC: normal controls; PNALT: Chronic hepatitis C with persistent normal alanine aminotrasferase; CLD: Chronic liver disease; HCC: hepatocellular carcinoma.

Figure 5

Scatter diagram representing the distribution values of IL-8 in the different study groups. NC: normal controls; PNALT: Chronic hepatitis C with persistent normal alanine aminotrasferase; CLD: Chronic liver disease; HCC: hepatocellular carcinoma.

Figure 6

ROC (Receiving operating characteristic) curve showing sFas, sTNFR-II and IL-2Rα in PNALT. Chronic hepatitis C with persistent normal alanine aminotrasferase) versus HCC (hepatocellular carcinoma) patients.

Figure 7

ROC (Receiving operating characteristic) curve showing IL-8 in PNALT (chronic hepatitis C with persistent normal alanine aminotrasferase) versus HCC (hepatocellular carcinoma) patients.