TUMOR-NECROSIS-FACTOR-ALPHA BEHAVIOR IN SERUM DURING RECOMBINANT-ALPHA-2B-INTERFERON TREATMENT OF CHRONIC VIRAL-HEPATITIS

Abstract: Objective: To investigate the behaviour of serum tumour necrosis factor-alpha (TNF-alpha) during alpha-interferon (alpha-IFN) treatment in patients with chronic viral hepatitis. Design: The study included 31 patients with chronic active hepatitis: five positive for hepatitis B surface antigen (HBsAg) and hepatitis B early antigen (HBeAg), and six positive for HBsAg, anti-HBe and hepatitis B virus (HBV) DNA; the remaining 20 were anti-hepatitis C virus (HCV) positive. All patients received 3 million units recombinant-alpha-2b-interferon three times weekly and were followed up for at least 3 months. Serum samples were collected at 0 and 24 h, and on days 1 5, 30 and 90. Responders were those patients whose transaminase levels returned to normal during alpha-IFN treatment. Methods: Serum TNF-alpha levels and anti-HCV were measured by enzyme immunoassay. Radioimmunoassays were used to detect HBsAg, HBeAg and anti-HBe. HBV-DNA was detected using a fluid-phase hybridization assay. Results: Basal serum TNF-alpha values were significantly higher in patients with chronic active hepatitis. TNF-alpha serum levels significantly increased 24 h after the first alpha-IFN injection and progressively returned to baseline values on days 15, 30 and 90. Anti-HCV-positive (nine out of 20) and HBsAg/anti-HBe/HBV-DNA-positive (three out of six) responders to alpha-IFN therapy had lower TNF-alpha serum levels than non-responders, reaching statistical significance after 3 months of treatment. HBsAg/HBeAg-positive responders (two out of five) had the highest TNF-alpha values. No correlation was found between the histological presence of cirrhosis and serum TNF-alpha levels. Conclusions: TNF-alpha is involved in the response to alpha-IFN therapy in chronic viral hepatitis