Glucocorticosteroid pretreatment may increase virologic response to interferon in hepatitis B 'e' antigen positive chronic hepatitis B

Interferon is an established treatment for chronic infection with hepatitis B virus. Although it is effective, response rates are not satisfactory. In order to increase response rates glucocorticosteroid withdrawal therapy has been proposed as a pretreatment strategy. The objectives of this review were to assess the effects of the sequential combination of glucocorticosteroids and interferon compared to interferon alone in the treatment of chronic hepatitis B. Glucocorticosteroid pretreatment was associated with a significantly higher frequency of loss of hepatitis B markers (HBeAg and HBV DNA), but had no significant effect on clinical outcomes.

Authors' conclusions: 

Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

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Background: 

Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon.

Objectives: 

The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events.

Search strategy: 

Eligible trials were identified through searches of The Cochrane Hepato-Biliary Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (Excerpta Medica Database) (1980 to May 2005), BIOSIS (1969 to May 2005), and reference lists of relevant articles. Further trials were sought through correspondence with authors of trials and pharmaceutical companies.

Selection criteria: 

Randomised clinical trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. We included trials irrespective blinding, publication status, or language.

Data collection and analysis: 

Three authors selected the trials independently and one extracted the data, which were then validated. We performed assessments of the outcome measures at the end of treatment and at six months and at maximal follow-up after the end of treatment with alfa interferon.

Main results: 

We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data.

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