Modulation of Serum Interleukin-18 Concentrations and Hepatitis B Virus DNA Levels During Interferon Therapy in Patients with Hepatitis B e-Antigen-Positive Chronic Hepatitis B

• Published in: Journal of interferon & cytokine research Vol. 30; no. 12; pp. 901 - 908
• Main Authors: Sylvan, Staffan P.E., Hellstrom, Ulla B.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.12.2010
• Subjects: Cells, Cultured; DNA, Viral - blood; Dosage and administration; Drug therapy; Genetic aspects; Hepatitis B; Hepatitis B e Antigens - blood; Hepatitis B e Antigens - immunology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Humans; Interferon; Interferon-alpha - immunology; Interferon-alpha - therapeutic use; Interleukin-18; Interleukin-18 - blood; MEDICIN; MEDICINE; Properties; Sweden
• ISSN: 1079-9907; 1557-7465; 1557-7465
• DOI: 10.1089/jir.2010.0042

The aim of this study was (1) to determine plasma values of interleukin-18 (IL-18) in patients with different clinical manifestations of hepatitis B (HB) and (2) to analyze the correlation between presence of circulatory levels of IL-18 and levels of HB virus (HBV) DNA during interferon-alpha (IFN-α)-induced HBe seroconversion in patients with chronic HB (CHB). The IL-18 levels in serum did not significantly differ between healthy control subjects (99 ± 25 pg/mL), HB-immune patients (85 ± 33), and asymptomatic carriers of HB surface antigen (144 ± 44 pg/mL). In contrast, anti-HBe (HBV DNA <10⁴ copies/mL, 555 ± 248, P < 0.05), anti-HBe (HBV DNA >10⁴ copies/mL, 280 ± 85, P < 0.05), and HBe-antigen-reactive (373 ± 108, P < 0.0001) patients with symptomatic CHB had significantly elevated levels in circulation compared with healthy control subjects (99 ± 25 pg/mL). An inverse correlation was found between serum HBV DNA copies and IL-18 levels during therapy (r = -0.54, P < 0.001). We consistently observed an IFN-α-induced suppression of viral replication, which was followed by the alanine aminotransferase (ALT) flare. There was a significant increase in IL-18 production after the ALT flare, where the peak of IL-18 preceded or coincided with the time of HBe seroconversion in patients who cleared the virus. These results suggest that IL-18 is involved in the pathogenesis of CHB and that IFN-α therapy can augment the production of IL-18 in patients with CHB.