Reuters Health Information (2005-06-29): Cessation of adefovir treatment in hepatitis B leads to rebound
Cessation of adefovir treatment in hepatitis B leads to rebound
Last Updated: 2005-06-29 17:00:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - The gains in viral
suppression and normalization of liver enzyme levels achieved by
treatment with adefovir dipivoxil for hepatitis B e antigen
(HBeAg)-negative chronic hepatitis B tend to be lost following
cessation of treatment, study results suggest.
Dr. Stephanos J. Hadziyannis, from Henry Dunant Hospital in Athens,
Greece, and his associates previously reported that adefovir treatment
of HBeAg-negative hepatitis B for 48 weeks led to improvements in liver
histology, viral load and alanine aminotransferase levels (see Reuters
Health report, February 26, 2003).
For their current report in the June 30th issue of The New England
Journal of Medicine, Dr. Hadziyannis's group followed the same cohort
for up to 240 weeks. Those previously assigned to adefovir treatment
were randomly assigned to continue treatment (n = 80) or to switch to
placebo (the adefovir-placebo group, n = 40). Those originally assigned
to placebo were switched to adefovir (placebo-adefovir group, n = 60).
The adefovir-placebo group experienced a rebound in serum hepatitis
B (HBV) DNA to baseline levels within 4 weeks of discontinuing the
drug. At 96 weeks, undetectable levels were reported in 71% of patients
in the continued-adefovir group, 76% in the placebo-adefovir group and
8% in the adefovir-placebo group.
Normal levels of alanine aminotransferase were documented in 73%,
80%, and 32%, respectively. In the majority of patients in the
adefovir-placebo group, enzyme levels had returned to pretreatment
values or higher.
At 144 weeks, resistance mutations had arisen in 5.9% of patients.
Among the eight patients in the adefovir-placebo group who underwent
repeat liver biopsy, there was a loss of improvement in histology
scores that had been observed at week 48, whereas patients receiving
adefovir experienced an overall improvement.
The adverse event profile during continuation treatment was similar to that observed during the previous 48 weeks.
Dr. Hadziyannis and his team state that "long-term therapy will be
needed for the majority of patients." Given the benefits of treatment
and the infrequent emergence of resistance, they conclude that adefovir
is "an excellent candidate for the long-term management of
HBeAg-negative chronic hepatitis B."
In a related editorial, Dr. Anna Suk-Fong Lok, from the University
of Michigan Medical Center in Ann Arbor, recommends "careful
deliberation before initiating treatment," with patient and physician
balancing the possibility of maintained response against the risk of
progressive liver disease, side effects, drug resistance and costs.
N Engl J Med 2005;352:2673-2681,2743-2746.