(Viread) Regimens Are Effective and Well-tolerated in Chronic
Hepatitis B Patients with Decompensated Liver Disease
nucleotide analog tenofovir
(Viread), especially when combined with emtricitabine
(Emtriva) -- the 2 drugs in the Truvada
coformulation -- was well-tolerated and produced
good hepatitis B virus (HBV) suppression and hepatitis
B "e" antigen (HBeAg) loss and seroconversion
in patients with decompensated liver disease,
according to data presented this past weekend
at the 60th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD)
years or decades, chronic
hepatitis B can lead to decompensated liver disease,
characterized by symptoms such as ascites (abdominal fluid
accumulation), portal vein hypertension, and hepatic encephalopathy.
Patients with advanced disease are considered difficult
to treat, but have an urgent need for effective therapy
to inhibit viral replication and slow further progression
of liver damage.
international team of researchers undertook a study to assess
the safety and tolerability of tenofovir, tenofovir
(Baraclude) in 112 patients with decompensated liver
disease (current or past Child-Pugh-Turcotte [CPT] score
> 7, but currently < 12) due to chronic
hepatitis B. Participants were randomly assigned to the
3 arms in a 2:2:1 manner.
participants (84%) were men, the median age was 52 years,
a majority (54%) were Asian, and 65% were initially HBeAg
negative. The mean CPT score was 7 and the mean MELD score
was 9.5. At baseline, one-third had creatinine clearance
< 80 mL/min (a sign of impaired kidney function). None
had previously used tenofovir or entecavir.
primary study end-point was safety, specifically "tolerability
failure," defined as adverse events resulting in permanent
treatment discontinuation. The researchers also assessed
kidney impairment, defined as a creatinine increase >
0.5 mg/dL from baseline or a phosphorus level < 2 mg/dL.
Decompensated liver disease is a risk factor for kidney
dysfunction, and studies of people with HIV indicate that
tenofovir can cause kidney problems in a small proportion
of at-risk individuals.
analysis of efficacy was a secondary objective. Patients
with insufficient viral suppression at week 8 or continued
detectable HBV DNA at week 24 or later could start open-label
tenofovir/emtricitabine, but were considered "failures"
in the efficacy analysis.
overall study was designed to last for 168 weeks; preliminary
48-week data were presented at AASLD.
week 48, "all treatments were well-tolerated and had
comparable safety and tolerability" in patients with
decompensated liver disease due to chronic hepatitis B, the
of participants taking tenofovir, 89% taking tenofovir/emtricitabine,
and 73% taking entecavir remained on their original
randomized treatment assignment at week 48.
failure occurred infrequently across all 3 arms: 7%
with tenofovir, 4% with tenofovir/emtricitabine, and
9% with entecavir (not a statistically significant difference).
of confirmed kidney impairment were 9%, 7%, and 5%,
respectively (also non-significant).
42%, and 23%, respectively, experienced serious adverse
events of any kind, but these were mostly considered
not study drug related.
patients discontinued therapy due to an adverse event,
only 1 of which was considered study drug related.
event and laboratory profiles were consistent with advanced
researchers identified no unexpected "safety signals"
for any of the study drugs.
participants received liver transplants, and none experienced
rates in the 3 arms were 4%, 4%, and 9%, respectively,
and none of the deaths were considered study drug related.
an intent-to-treat analysis, statistically similar proportions
of patients in the 3 arms achieved HBV DNA < 400
Week 12: 51% taking tenofovir, 47% taking tenofovir/emtricitabine,
and 50% taking entecavir;
- Week 24: 66%, 74%, and 68%, respectively;
- Week 48: 71%, 88%, and 73%, respectively.
participants with baseline lamivudine
(Epivir-HBV) resistance, 50%, 89%, 33%, respectively
had HBV DNA < 400 copies/mL at week 48.
of patients taking tenofovir, 76% taking tenofovir/emtricitabine,
and 55% taking entecavir had normal ALT at week 48.
(median change -1 in all arms) and MELD scores (median
change -2 in all arms) generally improved.
of patients in the tenofovir arm and 27% in the tenofovir/emtricitabine
arm experienced HBeAg loss, while 21% and 13%, respectively,
had HBeAg seroconversion.
entecavir recipients experienced HBeAg loss or seroconversion.
patients in any arm achieved hepatitis B surface antigen
tenofovir recipients developed mutations associated
wit tenofovir resistance.
overall incidence of renal [kidney] events was low and no
significant renal safety difference was observed between
groups in this vulnerable population," they continued.
"HBeAg loss or seroconversion was only observed in
the [tenofovir] containing regimens."
Memorial Hospital - LinKou, Taoyuan Hsien, Taiwan; Gilead
Sciences, Durham, NC; Chang-Gung Memorial Hospital - Kaohsiung,
Kaoshiung Hsien, Taiwan; Ege Universitesi Tip Fakultesi
Hastanesi, Izmir, Turkey; General Hospital of Athens, Athens,
Greece; Toronto General Hospital , Toronto, Ontario, Canada;
National Chen Kun University Hospital, Tainan, Taiwan; Hospital
of Infectious Diseases, Warsaw, Poland; Virginia Mason Medical
Center, Seattle, WA; Gordon and Leslie Diamond Centre, Vancouver,
BC, Canada; Servicio de Medicina Interna Hepatologia, Barcelona,
Spain; Hospital La Fe, Valencia, Spain; Medizinische Klinik
mit Schwerpunkt Hepatologie & Gastroenterology, Berlin,
Germany; University of Miami, Miami, FL.
Liaw, C Lee, US Akarca, and others. Interim Results of a
Double-Blind, Randomized Phase 2 Study of the Safety of
Tenofovir Disoproxil Fumarate, Emtricitabine plus Tenofovir
Disoproxil Fumarate, and Entecavir in the Treatment of Chronic
Hepatitis B Subjects with Decompensated Liver Disease. 60th
Annual Meeting of the American Association for the Study
of Liver Diseases (AASLD 2009). Boston. October 30-November
1, 2009. Abstract 122.