Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B.
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.


OBJECTIVE
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.


METHODS
Electronic searches of the controlled trial registers of The Cochrane Hepato-Biliary Group and The Cochrane Library, MEDLINE, BIOSIS, and EMBASE were combined (May 2000). Reading the bibliography of retrieved articles identified further trials. Alfa interferon-manufacturing companies were approached in order to inquire about any published and unpublished randomised trials.


METHODS
The analyses included randomised trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. The trials could be open, single blinded, or double blinded. No patient exclusion criteria were applied.


METHODS
Three reviewers independently selected the trials and one extracted the data, which were validated. Assessments of the outcome measures were performed at the end of treatment and at six months and at maximal follow up after the end of treatment with alfa interferon.


RESULTS
A total of 13 randomised trials including 790 patients were included. 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.


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.
Mellerup
M T
MT
The Copenhagen Trial Unit, Copenhagen University Hospital, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. mellerup@worldonline.dk
Krogsgaard
K
K
Mathurin
P
P
Gluud
C
C
Poynard
T
T
D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use*; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*
D000998:Antiviral Agents; D005938:Glucocorticoids; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha