http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10382631&dopt=Abstract
Update on clinical trials in the treatment of hepatitis B.
Pessoa MG, Wright TL.
Department of Veterans Affairs Medical Center, University of California, San
Francisco 94121, USA.
Chronic hepatitis B infection is a worldwide public health problem, which is
particularly important in countries of Asia. Interferon has long been available
for the treatment of patients with
active replication (hepatitis B virus (HBV) e antigen and HBV-DNA positive) with
evidence of chronic liver disease (elevated serum
alanine
aminotransferase
and chronic hepatitis on liver biopsy). Doses of interferon of 10 MU,
t.i.w. or 5 MU, q day for 16 weeks result in e antigen and HBV-DNA loss in
approximately one-third of individuals who meet these treatment criteria. The
major limitations of interferon are: (i) side effects of influenza-like
symptoms; (ii) need for parenteral administration; and (iii) concerns about
safety in patients with hepatic decompensation. Nucleoside and nucleotide
analogues have potent antiviral activity. The largest experience is with
lamivudine (3-thiacytadine), a reverse transcriptase inhibitor that was recently
approved by the USA Federal Drug Administration. At doses of 100 mg/day for 52
weeks, suppression of HBV replication is almost universal, with e antigen loss
and improvement in histology being achieved in one-third and two-thirds of
patients, respectively. The major advantages of lamivudine are: (i) good
tolerability; (ii) oral route of administration; and (iii) safety in patients
with hepatic decompensation. The major disadvantage is drug resistance, which is
observed with increasing frequency following prolonged administration. New
agents, such as adefovir dipivoxil, offer promise either alone or in combination
with lamivudine in the treatment of individuals who are 'treatment naive' as
well as in the treatment individuals who have developed lamivudine resistance.
Publication Types:
PMID: 10382631 [PubMed - indexed for MEDLINE]
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