antiviral efficacy and viral

liver411

Am J Gastroenterol 2002 Jul;97(7):1618-28

Nucleoside analogues for chronic hepatitis B: antiviral efficacy and viral
resistance.

Papatheodoridis GV, Dimou E, Papadimitropoulos V
Academic Department of Medicine, Hippokration General Hospital, Athens,
Greece.

[Medline record in process]


Nucleoside analogues have been recently introduced in the management of
chronic hepatitis B virus (HBV) infection. They mainly act by inhibition of
HBV polymerase activity resulting in decrease of viral replication. They are
administered orally, and most of them have an excellent tolerance and safety
profile. Lamivudine is the only nucleoside analogue licensed for chronic
hepatitis B. It has potent activity against HBV, and a 12-month course
achieves clearance of hepatitis B e antigen (HBeAg) in 20-30% of
HBeAg-positive patients and both biochemical and virological remission in
more than 65-70% of HBeAg-negative chronic hepatitis B patients. Famciclovir
and ganciclovir are less effective, whereas other nucleoside or nucleotide
analogues, such as adefovir, entecavir, and emtricitabine, are currently
under evaluation. Prolonged effective antiviral therapy is required for
eradication of chronic HBV infection, but long-term treatment with
nucleoside analogues has been found to be associated with progressively
increasing rates of viral resistance because of emergence of resistant HBV
mutant strains. Virological breakthroughs usually develop after the first 6
months of lamivudine monotherapy, and their rate ranges between 15% and 30%
at 12 months and exceeds 50% after 3 yr of therapy. Resistant HBV mutant
strains harbor point mutations in the HBV polymerase gene and predominantly
in the well-conserved YMDD motif. Although resistant HBV strains may have
impaired replication capacity compared with the wild HBV, their clinical
significance has not been completely clarified yet. No significant
biochemical or clinical event may develop in some cases, whereas severe
biochemical breakthroughs with or without deterioration of liver function
may develop in others. To date, there is no proven effective therapy for the
resistant HBV mutant strains, although adefovir and entecavir seem to be
interesting candidates.

PMID: 12135009, UI: 22130032