HBV
Viral Load at Week 4 of Lamivudine (Epivir-HBV) Treatment Predicts Response at
5 Years
Despite
the development of newer antiviral agents, lamivudine
(Epivir-HBV) remains a mainstay of treatment for chronic hepatitis
B virus (HBV) infection, in part due to its low cost. However, its long-term
efficacy is limited by the emergence of drug resistance.
As reported in
the December 2007 issue of Hepatology, Hong Kong researchers conducted
a study to determine the optimal time and HBV DNA level during early treatment
for the prediction of continued response after 5 years on lamivudine.
The
study included 74 hepatitis B "e" antigen (HBeAg) positive chronic hepatitis
B patients treated with lamivudine. HBV DNA levels were measured at baseline,
at weeks 2, 4, 8, 12, 16, 24, and 32, and at yearly intervals until year 5.
Results
•
17 patients achieved an ideal response, defined as HBV DNA level < 2000 copies/mL
(400 IU/mL), HBeAg seroconversion, alanine aminotransferase (ALT) normalization,
and absence of YMDD drug resistance mutations at year 5.
•
Receiver operating characteristic (ROC) curves showed good predictions as early
as week 4.
•
The areas under the ROC curve for weeks 4 and 16 were 0.89 and 0.94, respectively.
•
Predictive indices revealed 4 and 3.6 log copies/mL (2000 and 800 IU/mL), respectively,
to be the best cutoff HBV DNA levels for 4 and 16 weeks.
•
All patients with HBV DNA levels below these respective cutoff levels at 4 and
16 weeks achieved an ideal response at year 5.
•
Patients with HBV DNA levels above these cutoff values had a 83.8% and 87.7% likelihood,
respectively, of not achieving an ideal response at year 5.
Conclusion
Based
on these findings, the authors concluded, "The measurement of the HBV DNA
levels at week 4 of lamivudine treatment should be performed in all patients to
predict the long-term outcome."
"[T]reatment can be continued
for those with HBV DNA levels of less than 4 log copies/mL (2000 IU/mL),"
they added. "The addition of or switch to alternative antiviral agents should
be considered for patients who fail to achieve this early target."
Alternative
approved agents that may be used for this purpose include adefovir (Hepsera),
entecavir (Baraclude), and telbivudine (Tyzeka).
Departments of Medicine
and Nursing Studies, University of Hong Kong, Queen Mary Hospital, Hong Kong.
01/08/08
Reference MF
Yuen, DY Fong, DK Wong, and others. Hepatitis B virus DNA levels at week 4 of
lamivudine treatment predict the 5-year ideal response. Hepatology 46(6):
1695-1703. December 2007.
