Core variability does not affect response to interferon alpha in HBeAg negative chronic hepatitis B.
OBJECTIVE
The pre-core stop codon variant (A 1896) of hepatitis B virus (HBV) has been associated with chronic active liver disease with acute exacerbations and a high relapse rate after an initial response to alpha-interferon (IFN-alpha) therapy. Poor sustained response has been correlated with a high prevalence of mutations in the core region, potentially enabling escape from the immune system. The aim of this study was to analyse the predictive factors of response to IFN-alpha in such patients.


METHODS
We studied the baseline clinical, biochemical, histological, serological and virological parameters in 30 hepatitis B s antigen positive (HBsAg-positive)/hepatitis B e antigen negative (HBeAg-negative) Greek patients with chronic liver disease. The patients were selected from a cohort who received IFN-alpha for 24 weeks. These were divided into three groups of ten sequential patients: those with no response to IFN-alpha treatment, those who relapsed after an initial response, and those with a sustained response. Serum HBV DNA was measured by a liquid hybridisation method, and the anti-HBc IgM was quantitated by the IMx analyser. The amino-acid sequence of core protein residues 40-89, a region where a clustering of mutations has been detected previously in severe hepatitis, was compared with a sequence from an HBeAg positive patient with chronic liver disease.


RESULTS
Multiple logistic regression analysis showed that the initial response to IFN-alpha could be predicted by pre-treatment absence of HBcAg staining in the liver and high ALT values, but no parameter could predict sustained response. The pre-treatment extent and pattern of aminoacid substitutions in the core region sequenced was similar in all groups studied and was not associated with IFN-alpha response.


CONCLUSIONS
In HBsAg-positive/HBeAg-negative patients with chronic liver disease, response to IFN-alpha therapy was not correlated with genomic variability of the core region. Other parameters such as pre-treatment HBcAg positivity in the liver and alanine aminotransferase values indicative of disease activity before treatment were associated with initial IFN-alpha response.
Academic Department of Medicine, Hippokration General Hospital, Athens, Greece.
A
A
Alexopoulou
A M
AM
Owsianka
G
G
Kafiri
S P
SP
Dourakis
W F
WF
Carman
S J
SJ
Hadziyannis
D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D003062:Codon; D005260:Female; D014644:Genetic Variation; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D016896:Treatment Outcome
D000998:Antiviral Agents; D003062:Codon; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha