Entecavir (Baraclude) Produces Sustained Viral Suppression with
Little Resistance in HBeAg Positive Chronic Hepatitis B Patients
Extended treatment with the nucleoside analog entecavir
(Baraclude) for 5 years maintained or increased rates
of HBV viral load suppression and ALT normalization
seen after initial shorter duration therapy in hepatitis
B "e" antigen (HBeAg) positive patients,
according to a report in the January
4, 2010 advance online edition of Hepatology.
Additional patients achieved HBeAg loss and seroconversion,
entecavir remained well tolerated, and only 1 person
has demonstrated potent antiviral activity and produced
favorable outcomes during an initial treatment period of
48 weeks. But
patients may relapse after discontinuing therapy, suggesting
that longer treatment duration may be beneficial. Prolonged
treatment may increase the risk of resistance, however, which
has proven to be a barrier to long-term treatment with lamivudine
(Epivir-HBV), an older HBV drug.
the present study, Ting-Tsung Chang from National Cheng Kung
University in Taiwan and an international team of colleagues
assessed extended entecavir treatment for up to 5 years.
The analysis included participants from study ETV-022, which
previously demonstrated that 0.5 mg daily entecavir was superior
to lamivudine at suppressing HBV DNA in previously untreated
HBeAg positive chronic hepatitis B patients treated for 48 weeks.
A subset of 183 participants treated with entecavir opted to
enroll in an open-label extension study, ETV-901.
The entecavir long-term cohort consisted of 146 patients who
received 0.5 mg daily entecavir for at least 1 year in ETV-022
and then -- with a gap of no more than 35 days -- took 0.1 mg
daily entecavir in ETV-901 for up to 240 weeks. Some patients
had a period of combination therapy with entecavir plus lamivudine.
Most people who had already achieved HBeAg seroconversion did
not enroll in the extension, so this cohort included a higher
proportion of serological non-responders.
5 years on entecavir, 94% of long-term cohort participants
had HBV DNA < 300 copies/mL.
achieved normal alanine transaminase (ALT) levels.
addition to those patients who achieved serological responses
during ETV-022, 23% achieved HBeAg seroconversion and 1.4%
experienced hepatitis B surface antigen (HBsAg) loss during
5 years, entecavir resistance emerged in only 1 patient.
total of 47 patients discontinued treatment prior to 240
safety profile of entecavir was consistent with findings
at 48 weeks, with no unexpected adverse events.
conclusion, the study authors wrote, "Extended therapy
with entecavir through 5 years maintained or increased rates
of HBV DNA suppression and ALT normalization. Additional patients
also achieved HBeAg loss and seroconversion."
"Entecavir provides sustained viral suppression with minimal
resistance during long-term treatment of HBeAg positive chronic
hepatitis B," they added.
"The importance of maintaining prolonged HBV DNA suppression
to avoid or minimize the long-term complications of chronic
hepatitis B has been recognized in several long-term studies
of disease progression and outcome," they noted in their
discussion. "It has also been shown that even patients
with low-level HBV DNA viremia (below 104 to 105 copies/mL)
are at risk of fibrosis, cirrhosis, and hepatocellular carcinoma."
chronic hepatitis B treatment recommendations advocate sustained
suppression of HBV DNA as the primary goal of antiviral therapy,"
they continued. "The rate of entecavir resistance remains
rare over long-term therapy and distinguishes it from other
HBV antivirals with long-term data. Entecavir's resistance profile
is believed to result from its potent viral suppression and
high genetic barrier to resistance."
College, National Cheng Kung University, Tainan, Taiwan, ROC;
Queen Mary Hospital, Hong Kong, China; Kangnam St. Mary Hospital,
The Catholic University of Korea, Seoul, Korea; Foothills Provincial
General Hospital, University of Calgary, Calgary, Canada; Hospital
Universitario Clementino Fraga Filho, Universidade Federal do
Rio de Janeiro, Rio de Janeiro, Brazil; Department of Gastroenterology,
University of São Paulo School of Medicine, São
Paulo, SP, Brazil; Department of Hepatology and Liver Transplantation,
Cedars-Sinai Medical Center, Los Angeles, CA; Department of
Infectious Diseases and Hepatology, Nicolaus Copernicus University,
Bydgoszcz, Poland; Department of Hepatology and Gastroenterology,
Cliniques St Luc, Brussels, Belgium; University of Hawaii, Honolulu,
HI; Bristol-Myers Squibb Co. (BMS), Research and Development,
Wallingford, CT; Bristol-Myers Squibb Co., Research and Development,
TT Chang, CL Lai, S Kew Yoon, and others. Entecavir treatment
for up to 5 years in patients with hepatitis B e antigen-positive
chronic hepatitis B. Hepatology (Abstract).
January 4, 2010 (Epub ahead of print).