Serum levels of cytokines in hepatitis C-related liver disease: a longitudinal study.

BACKGROUND

Elevated serum cytokine levels are found in patients with acute and chronic hepatitis B. However, little is known about the development and progression of cytokines in hepatitis C infection. We conducted this study to evaluate the change and clinical significance of cytokines in the different stages of hepatitis C infection.

METHODS

Circulating interleukin-1 beta (IL-1 beta), interleukin-2 receptor (IL-2r), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay in 29 patients with acute hepatitis C (AHC), 43 patients with chronic hepatitis C (CHC), 40 patients with liver cirrhosis (LC) and positive serum anti-hepatitis C antibody (anti-HCV), 36 patients with hepatocellular carcinoma (HCC) and positive anti-HCV and 30 normal controls. A cohort of patients with chronic hepatitis C was monitored for a median of seven years.

RESULTS

Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels were significantly elevated in all patient groups compared with controls (p < 0.05). The serum IL-1 beta, IL-2r and TNF-alpha levels in patients with LC or HCC were higher than that in patients with AHC or CHC (p < 0.05). In the longitudinal follow-up, 12 patients with chronic hepatitis at enrollment in the study developed liver cirrhosis. For these patients, serum levels of IL-1 alpha, IL-2r and TNF-alpha were higher in liver cirrhosis than in chronic hepatitis (p < 0.05). In addition, the serum concentrations of these cytokines correlated better with indices of hepatic dysfunction (prothrombin time and indocyanine green retention ratio) than with parameters of hepatic inflammation (alanine aminotransferase and aspartate aminotransferase).

CONCLUSIONS

Serum IL-1 beta, IL-2r, IL-6 and TNF-alpha levels are elevated in patients with hepatitis C-related liver diseases, especially in LC and HCC patients. These levels reflect hepatic dysfunction better than liver inflammation parameters, which might explain the higher serum concentrations of cytokines in LC patients.