(Baraclude) and Tenofovir (Viread) Rescue Therapy for Chronic
Hepatitis B Patients with Advanced Fibrosis and Prior Treatment
A "rescue therapy" regimen combining
(Baraclude) and tenofovir
(Viread) is safe and effective for chronic
hepatitis B patients with advanced liver disease
who have experienced past treatment failure or
developed extensive drug resistance, according
to a study presented this month in Boston at the
60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD 2009).
this open-label cohort study, investigators from 8 referral
centers in Europe assessed the efficacy and safety of tenofovir
in treatment-experienced hepatitis
B patients with advanced liver
treatment with single nucleoside/nucleotide analog drugs
as sequential monotherapy has left many patients with hepatitis
B virus (HBV) that harbors multiple resistance mutations,
the researchers noted as background. Drug resistance renders
older therapies less effective or ineffective, putting patients
with advanced liver
fibrosis or cirrhosis
at risk of further damage due to hepatic "flares,"
or episodes of worsening disease.
the 39 study participants, more than half were hepatitis
B "e" antigen (HBeAg) positive. They had multidrug
resistant HBV or a history of only partial response to previous
treatment. The median age was 48 years, and patients had
used an average of 3 (range 1-6) past treatment regimens.
At baseline, the median ALT level was 1.2 x upper limit
of normal (ULN) and the median HBV DNA level was 1.7 x 10(4)
median treatment duration after initiating combination
therapy was 10.5 months (range 1-42 months).
this period, no significant clinical side effects were
median HBV DNA level dropped significantly after starting
the combination regimen, by 3.5 log (range 0-8 log;
P < 0.0001).
80% (31 of 39 patients) achieved undetectable HBV DNA
(< 80 IU/mL).
DNA decline was accompanied by a significant ALT decrease
(median 0.68 x ULN; P = 0.001).
patients with detectable HBV DNA were treated for less
than 6 months.
patients experienced HBeAg loss (after 18, 21, and 24
person showed hepatitis B surface antibody (HBs) seroconversion.
with liver cirrhosis at baseline did not develop clinical
2 patients with cirrhosis who had undetectable HBV DNA
nevertheless developed hepatocellular carcinoma.
was no significant decrease in adherence among patients
taking the 2 medications.
on these findings, the investigators concluded, "Rescue
therapy with entecavir and tenofovir in HBV monoinfected
patients harboring complex viral resistance patterns or
showing only partial antiviral responses to preceding therapies
was highly efficient, safe, and well tolerated in patients
with advanced liver disease."
they added, "More data are certainly needed to judge
about the long-term safety, efficacy and prevention of emergence
of new viral mutations in this difficult to treat patient
St. Georg, Liver Center Hamburg IFI Institute, University
of Hamburg, Germany; University Hospital Hamburg Eppendorf,
Hamburg, Germany; Hotel Dieu Hospital Lyon, Lyon, France;
University Hospital Hamburg Eppendorf, Hamburg, Germany;
University Medical Center, Rotterdam, Netherlands; Charite
University Medical Center, Berlin, Germany; Fondazione IRCCS
Maggiore Hospital, University of Milan, Italy; Service d
Hepato-Gastroenterologie, Universite Pierre et Marie Curie,
Paris, France; Hospital Vall de Hebron, Barcelona, Spain;
Goethe University Hospital, Frankfurt, Germany.
Petersen, M Lutgehetmann, F Zoulim, and others. Entecavir
and Tenofovir combination therapy in chronic Hepatitis B:
Rescue therapy in patients with advanced fibrosis and multiple
previous treatment failures. Results from an international
multicenter cohort study. 60th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD 2009).
Boston. October 30-November 1, 2009. Abstract 405.