Likelihood of Adefovir (Hepsera) Resistance in Nucleoside-naive Hepatitis B Patients
Adefovir
(Hepsera) Tablet
In
a study described in the January 22, 2008 advance online edition of the Journal
of Viral Hepatitis, Spanish researchers assessed initial virological response
to adefovir (Hepsera) treatment for chronic
hepatitis B, aiming to identify patients with suboptimal response and to determine
the incidence of adefovir-resistance mutations.
All patients treated with
adefovir at their clinic for at least 12 months were evaluated for virological
response and adefovir resistance. Initial virological response was defined as
a reduction in HBV DNA of at least 4 log10 IU/mL at month 6. Among the 42 patients
analyzed, the mean treatment duration was 23 months. Most (88%) were hepatitis
B "e" antigen (HBeAg) negative, 76% had HBV genotype D, half had previously
been treated with lamivudine (Epivir-HBV), and
62% of these had evidence of lamivudine resistance.
Results
•
40.5%
of the patients experienced initial virological response.
•
Higher
baseline alanine aminotransferase (ALT) level was the only factor associated with
initial response (P = 0.043).
•
77%
of patients with initial virological response achieved undetectable HBV DNA at
month 12, compared with only 5% of those without initial response (P < 0.001).
•
5
patients (12%) developed adefovir-resistance mutations:
•
4 with rtN236T;
•
1 with an rtV207L change, which has not previously been reported.
•
The
rtV207L mutation was accompanied by HBV viral rebound and an ALT flare.
•
The
cumulative probability of adefovir-resistance mutations was 5% at 12 months and
17% at 24 months.
Conclusion
"Initial
virological response defined as a reduction > 4 log10 IU/mL in HBV DNA
at month 6 is a useful tool to predict virological response at month 12 and to
identify patients with suboptimal response to adefovir," the authors concluded.
They added that, "Cumulative probability of adefovir resistance [was]
higher than previously reported" for nucleoside/nucleotide-naive patients.
2/29/08
Reference A
Gallego, J Sheldon, J Garcia-Samaniego, and others. Evaluation of initial virological
response to adefovir and development of adefovir-resistant mutations in patients
with chronic hepatitis B. Journal of Viral Hepatitis. January 22, 2008
[Epub ahead of print].
Results