Do liver IL-12 levels predict sustained response to ifn-α therapy in children with chronic hepatitis B?

Abstract

The aim of this study is to investigate the immunoregulatory role of interleukin-12 and interferon-gamma in children with chronic hepatitis B who are treated with interferon-alpha therapy. The patients were divided into 2 groups: Group I included 16 children with naive chronic replicative hepatitis B infection, and Group II included 6 children who are inactive hepatitis B virus (HBV) carriers. Group I received interferon-alpha subcutaneously (10 mU/m(2)/dose), 3 times a week during 4 months. Initial serum alanine aminotransferase (ALT) levels, hepatitis B serologic markers, serum interleukin-12 and interferon-gamma levels were measured. In Group I, laboratory tests were re-evaluated in the second and fourth months. Liver biopsy was performed in all patients and samples were used for tissue interleukin-12 level evaluation and histopathological examination. Hepatic activity index (HAI) and serum interferon-gamma were significantly higher in Group I (P < 0.05). Initial tissue interleukin-12 levels in Group I were low but a significant increase was observed at the fourth month (P < 0.05). While responder patients in Group I had marked elevation of tissue interleukin-12 levels, nonresponders did not reveal considerable changes at the fourth month evaluation. A negative correlation was found between serum HBV-DNA copies and interferon-gamma levels prior to therapy (P < 0.01, r: -0.66). The analysis of cytokine levels with serum transaminases demonstrated a positive correlation between the tissue interleukin-12 levels at the fourth month and serum ALT levels at the beginning and second month of the therapy (r: 0.77, P < 0.05 and r: 0.92, P < 0.05, respectively). This is the first study emphasizing the relationship between tissue cytokine levels and therapy success. Understanding the course of chronic hepatits B in the pediatric population will help us to clarify some debates on the treatment.