(Viread) Is Similarly Effective in Chronic Hepatitis B Patients Regardless of
Liver Cirrhosis Status
(Viread) is the most recently approved nucleoside/nucleotide drug for the
treatment of chronic hepatitis B virus (HBV) infection;
it is also approved as a component of antiretroviral
therapy for HIV, and is included in the Truvada
and Atripla fixed-dose combination
In a presentation at the 44th Annual Meeting
of the European Association for the Study of the Liver (EASL 2009) last month
in Copenhagen, researchers reported that over 96 weeks, tenofovir worked well
in people with or without liver
It is well known that interferon-based
therapy for chronic hepatitis B or C works better and is more easily tolerated
in people who have not yet developed advanced liver damage, but the influence
of cirrhosis on the effectiveness of nucleoside/nucleotide agents is unclear.
present analysis included cirrhotic patients who received tenofovir for 96 weeks
in studies GS-174-0102 (Study 102) and GS-174-0103 (Study 103), two Phase 3 hepatitis
B registration trials sponsored by tenofovir manufacturer Gilead Sciences.
102 included hepatitis B "e" antigen (HBeAg) negative chronic hepatitis
B patients and Study 103 included HBeAg positive patients. Otherwise, the study
protocols were the same. About three-quarters of participants were men, about
60% were white, about 30% were Asian, and the median ages were 47 in the cirrhotic
group and 39 years in the non-cirrhotic group.
At baseline, all participants
had elevated ALT (median 92 U/L in the cirrhotic group and 108 in the non-cirrhotic
group) and HBV DNA >100,000 copies/mL. Of the total 426 participants in both
studies combined, 81 (19%) had cirrhosis: 47 in the HBeAg negative group and 34
in the HBeAg positive group.
Participants were randomly assigned (2:1)
to receive 300 mg tenofovir or 10 mg adefovir
(Hepsera) once-daily for 48 weeks. Patients who underwent liver biopsy at
week 48 were eligible to receive open-label tenofovir for an additional 7 years,
with an option to add another drug with dual activity against HBV and HIV -- emtricitabine
(Emtriva; combined with tenofovir in the Truvada combination pill) -- after
week 72 if they still had confirmed HBV DNA > 400 copies/mL.
Similar proportions of cirrhotic and non-cirrhotic patients achieved HBV DNA suppression
< 400 c/mL at week 96:
90% vs 85%, respectively, in an intent-to-treat analysis;
97% versus 95%, respectively, in an observed or as-treated analysis.
No cirrhotic patients, but 7 non-cirrhotic patients, experienced viral breakthrough
over 96 weeks (> 1 log increase or rising above 400 copies/mL after
falling below this level).
Among participants who remained on telbivudine, 83% of cirrhotic patients and
78% of non-cirrhotic patients had normal ALT levels at week 96 (median 34 and
35 U/L, respectively).
Among HBeAg positive participants with 96 week serology results available, 9 of
29 cirrhotic patients (31%) and 25 of 103 non-cirrhotic patients (24%) experienced
HBeAg seroconversion to anti-HBe, not a statistically significant difference.
2 HBeAg positive patients with cirrhosis (6%) experienced hepatitis B surface
antigen (HBsAg) seroconversion to anti-HBs, compared with none of the HBeAg negative
Treatment was well-tolerated overall, although there was a non-significant trend
toward more adverse events (AEs) among patients with cirrhosis:
11% of cirrhotic and 13% of non-cirrhotic patients experienced grade 3 or 4 AEs;
15% and 9%, respectively, experienced serious AEs;
31% and 23%, respectively, experienced grade 3 or 4 laboratory abnormalities.
1 patient with cirrhosis developed hepatocellular
No patients with cirrhosis progressed to clinically evident liver decompensation.
No cirrhotic patients developed kidney toxicity as indicated by confirmed creatinine
increase of 0.5 mg/dL, creatinine clearance < 50 mL/min, or phosphorous <
2 mg/dL (a potential concern with both tenofovir and adefovir).
No tenofovir-associated resistance mutations were detected through week 96.
on these findings, the researchers concluded, "The efficacy and safety of
[tenofovir] at 96 weeks was not influenced by the existence of cirrhosis at onset
of therapy and was comparable among cirrhotic and non-cirrhotic patients with
good tolerability in both populations."
Hospital General Universitari
Vall d'Hebron, Barcelona, Spain; Henry Dunant Hospital, Athens, Greece; Hopital
Claude Huriez, CHRU Lille, France; Intern Klinika, UVN Praha, Prague, Czech Republic;
Toronto General Hospital, Toronto, Canada; AW Morrow Gastroenterology & Liver
Center, Royal Prince Alfred Hospital, Camperdown, Australia; Digestive Disease
Institute, Virginia Mason Medical Center, Seattle, WA; Klinik & Poliklinik
f. Innere Medizin, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany; Toronto
Western Hospital, University of Toronto, Toronto, Canada; Hopital Beaujon, Clichy,
France; Gilead Sciences, Durham, NC.
Buti, S Hadziyannis, P Mathurin, and others. Two
years safety and efficacy of tenofovir disoproxil fumarate (TDF) in patients with
HBV-induced cirrhosis. 44th Annual Meeting of the European Association for
the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009. Abstract
2009 MAIN PAGE
Conference on Retroviruses and Opportunistic Infections (CROI 2009)
by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
HIV and AIDS Treatment
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of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
- Coverage by HIV and Hepatitis.com, February 8 - 11, 2009, Montreal