Recombinant interferon‐α therapy for acute hepatitis B: a randomized, double‐blind, placebo‐controlled trial

Abstract

In spite of the availability of hepatitis B vaccine, acute hepatitis B continues to be a worldwide problem for which no specific therapy is available. We investigated the safety and the effectiveness of recombinant interferon-alpha2b (rIFN-alpha2b) in the treatment of acute hepatitis B by determining overall severity and duration of symptoms, time required to clear viral antigens and hepatitis B virus (HBV) DNA, and titre of antibodies to hepatitis B surface antigen (HBsAb), 24 weeks after the onset of therapy. One hundred patients were randomly assigned to treatment with either 3 million units (MU) (n = 34) or 10 MU (n = 33) rIFN-alpha2b or to placebo (n = 33), three times weekly for 3 weeks. Follow-up was for 24 weeks. A significantly shorter duration of the symptoms and signs of acute hepatitis was observed in patients who received 3 MU rIFN-alpha2b compared with those who received 10 MU rIFN-alpha2b or placebo. Twenty-one weeks post-therapy, patients treated with 10 MU rIFN-alpha2b showed a significantly higher geometric mean HBsAb titre than those treated with placebo (85.1 vs 35.5 IU l-1, P < 0.05). rIFN-alpha2b administration was well tolerated even in jaundiced patients. No serious side-effects were observed necessitating reduction in dose or discontinuation of the drug. The effect of rIFN-alpha2b on transition of HBV infection to chronicity could not be evaluated in this trial because such an unfavourable course was not seen in any of the treated or the control patients. In conclusion, rIFN-alpha2b was safe in acute hepatitis B, and at low dose was found to ameliorate symptoms and to shorten significantly the duration of illness.

Management of hepatitis B

“…118 There have been no prospective studies of nucleoside analogues in typical acute hepatitis B, but case reports and small series in severe or prolonged acute hepatitis and HBV-related liver failure suggest some benefit of early therapy. [119][120][121][122] The serious nature of acute liver failure and the safety of nucleoside analogue therapy support its use in patients at the first sign of severe injury or impending liver failure (prolongation of prothrombin time or hepatic encephalopathy), particularly since a proportion of patients will be referred for emergency liver transplantation and require prophylaxis against recurrence, which usually includes nucleoside analogue therapy.…”

Treatment of special populations with chronic hepatitis B infection

“…However, a randomized study did not demonstrate any difference in the rate of biochemical improvement or of HBsAg loss [77,78]. Several years ago, a randomized trial was conducted in Greece in patients with acute icteric hepatitis B using IFN-a 2b with no benefit, since all patients lost HBsAg and seroconverted to anti-HBs [79]. In a recent study of ETV in six patients with fulminant hepatitis B, five of them lost HBsAg and seroconverted to anti-HBs, while apoptosis parameters measured during the study demonstrated a rapid decline [76].…”

Therapy of Acute and Fulminant Hepatitis B

“…However, it was explored as an option for acute hepatitis B in the past, without obvious deleterious effects, but also without evidence of benefit [44]. Still interferon might be an option for cases that are not too severe, but prolonged without significant HBsAg decline during the early weeks of infection.…”