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Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D

Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

Correspondence to:
Correspondence to:
Dr A Erhardt
Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr 5, D-40225 Düsseldorf, Germany; erhardt{at}uni-duesseldorf.de

ABSTRACT
Background an aims: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated.

Patients and methods: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases.

Results: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2xupper limit of normal) as independent positive predictive parameters of IFN response.

Conclusions: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; IFN-, interferon alfa; ETR, end of treatment response; SR-6, sustained response six months post treatment; SR-12, sustained response 12 months post treatment; HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase; ULN, upper limit of normal

Keywords: virus; hepatitis B; genotype; therapy; interferon

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Gut 2005 54: 893. [Extract] [Full Text] [PDF]

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