A controlled trial of high dose interferon, alone and after prednisone withdrawal, in the treatment of chronic hepatitis B: long term follow up.

Abstract

This study was designed to evaluate the safety and effectiveness of high dose interferon, with or without prednisone pretreatment, in patients with chronic hepatitis B. Patients were randomised to two treatment groups: group I (n=26) received six weeks of prednisone followed by a two week, drug free period, and then 10 million units (MU) ofinterferon alfa-2b three times weekly subcutaneously for 16 weeks; group II (n=24) were used as controls for 24 weeks and then treated with interferon. Loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)-DNA, with a return to normal alanine aminotransferase (ALT) activity, was seen in 16 of 26 group I patients (61.5%), in one group II patient (4/2%) during the control phase, and in 13 of 23 group II patients (56/5%) after interferon. Three of 26 (11.5%) in group I and one of 23 (4/3%) in group II eliminated the surface antigen (HBsAg). There were no statistically significant differences in response between groups I and II. Liver biopsies carried out in 20 patients showed that responders had a noticeable reduction in inflammation and disappearance of core antigen in liver tissue, changes not seen in non-responders. On long term follow up (four years), nine out of 28 responders (32-/1%) eliminated HBsAg, and four initial non-responders had a late seroconversion.(Gut 1993; supplement: S91-S94) Patients in group II were followed without treatment for 24 weeks (control period) and then interferon alfa-2b was given in the same dose and for the same duration as in group I. Both groups were followed for 24 weeks. Efficacy was determined by HBeAg and hepatitis B surface antigen (HBsAg) seroconversion, a return to negative of HBV-DNA, ALT normalisation, and histological activity as measured by the Knodell index score. Safety was determined by assessing the number and type of adverse reactions, reduction of doses, and rates of withdrawal.

Virological response to interferon therapy of chronic hepatitis B as measured by a highly sensitive assay

“…after IFN), however, the virological response rate was higher in the Pred/IFN group, 50% vs. 10% in the IFN group ( P < 0.0001). This strong impact of prednisolone withdrawal agrees with some [4,17], but not all [8,14] previous studies. The reason for these conflicting data is obscure.…”

“…pegylated interferons, higher doses or drug combinations) may further enhance IFN response rates. Although conflicting data have been presented [8,14,15], several studies have reported beneficial effects of steroid pretreatment [4,6,16–18], and recently steroid priming was found to enhance the response to lamivudine [19]. It is possible that measuring the virological response with more sensitive assays may improve our understanding of therapy.…”

Role of steroid priming in the treatment of chronic hepatitis B

“… 23 Perez et al also reported the better effects of steroid priming and interferon in a long‐term follow‐up study. 24 Lin et al recently also reported the long term sustained effect of the treatment. 25 Therefore, it would appear that effects obtained by using steroid withdrawal therapy followed by anti‐viral agents in the treatment of chronic hepatitis B seem to last long term.…”