Abstract
The mechanisms underlying hepatic inflammation and fibrogenesis in chronic hepatitis B (CHB) are complex and several cytokines are involved. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily which also acts as a cytokine. This study was conducted to evaluate serum soluble TWEAK (sTWEAK) levels in noncirrhotic CHB patients.Fifty-two treatment naive CHB patients and 30 healthy controls were included in the study and serum sTWEAK concentrations were measured using commercially available ELISA kits.Mean serum sTWEAK concentration was significantly lower in CHB group than healthy controls (189.6 ± 63.3 pg/mL in CHB group and 297.6 ± 61.5 pg/mL in control group, P < 0.001). According to the degree of necroinflammation in liver biopsies mean sTWEAK concentrations were found to be 168.14 ± 51.51, 206.96 ± 58.51, and 223.62 ± 78.88 pg/mL in patients with mild, moderate, and severe inflammation, respectively, and the difference between groups was statistically significant (P = 0.022). sTWEAK concentration was also found to be significantly higher in patients with advanced fibrosis in liver biopsy samples (169.59 ± 52.02 and 211.17 ± 68.22 pg/mL in patients with mild and advanced fibrosis, respectively, P = 0.016). Receiver operating characteristic (ROC) curves were obtained in CHB group to differentiate patients with advanced fibrosis from patients with mild fibrosis. Area under curve (AUC) was 0.676 (95% Cl; 0.526-0.825) for sTWEAK and for the specified cut-off value of 213.67 pg/mL sensitivity and specificity were 60% and 81.4%, respectively. ROC curve for sTWEAK to differentiate patients with severe inflammation revealed an AUC of 0.664 (95% Cl; 0.450-0.878). A cut-off value of 243.27 pg/mL yielded 54.5% sensitivity and 82.9% specificity.Serum sTWEAK concentration is decreased in treatment naive CHB patients. Further studies with simultaneous determination of circulating sTWEAK concentrations and TWEAK and factor-inducible 14 (Fn14) expressions in the liver biopsy samples would clarify the exact association of TWEAK/Fn14 pathway in the pathogenesis of CHB.