By Liz Highleyman

Several nucleoside/nucleotide analog drugs are approved for the treatment of chronic hepatitis B virus (HBV) infection, though the long-term effectiveness of some is limited by the emergence of drug resistance.

Tenofovir (Viread), which is being evaluated as an anti-HBV treatment in the U.S., is already approved for the treatment of HIV. The European Commission approved tenofovir for chronic hepatitis B in April.

Several presentations at the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan focused on tenofovir for chronic hepatitis B, including data from the pivotal Studies 102 and 103.

In another analysis reported at the conference, researchers assessed the safety and efficacy of tenofovir in the subset of patients in these two Phase 3 trials who had pre-existing liver cirrhosis at study entry.

Study 102 included hepatitis B "e" antigen (HBeAg) negative participants, while Study 103 included HBeAg positive patients. All participants started the study with elevated ALT and HBV DNA >100,000 copies/mL. They were randomly assigned in a 2:1 manner to receive 300 mg tenofovir or 10 mg adefovir (Hepsera) once daily for 48 weeks.

Results

• 123 patients, or 19% of all participants in the 2 studies combined, had cirrhosis at baseline:

• 72 HBeAg negative and 51 HBeAg positive;

• 81 assigned to the tenofovir arm and 42 assigned to adefovir.

• Baseline characteristics were similar overall in cirrhotic and non-cirrhotic (n=511) participants, but those with cirrhosis were older and had a higher mean Knodell necroinflammatory score of about 9.

• In the cirrhotic subgroup, most were men (80%) and Caucasian (59%), with a mean age of about 45 years and a mean baseline HBV viral load of about 7.50 log copies/mL.

• At 48 weeks, tenofovir was shown to be effective in a large proportion of cirrhotic patients:

• 85% with HBV suppression < 400 copies/mL;

• 79% with histological response;

• 69% with biochemical response (ALT normalization).

• These results were consistent with those observed for the overall study population.

• Tenofovir was significantly more likely than adefovir to produce HBV DNA suppression < 400 copies/mL (85% vs 48%; P<0.001).

• Histological and ALT responses were similar in the tenofovir and adefovir arms.

• Tenofovir was well tolerated overall, with a safety profile in cirrhotic patients comparable to that of patients without cirrhosis.

• There were fewer serious adverse events in the tenofovir arm compared with the adefovir arm.

• The investigators reported "good renal tolerability" (important because tenofovir has been associated with potential kidney toxicity in susceptible HIV patients).

Conclusion

Based on these findings, the investigators concluded, "Tenofovir demonstrated high efficacy, good tolerability, and superior HBV DNA suppression compared with adefovir in subjects with compensated cirrhosis due to chronic hepatitis B."

Hospital General Universitari Vall D Hebron, Barcelona, Spain; Henry Dunant Hospital, Athens, Greece; Hopital Claude Huriez, CHRU Lille, Lille, France; UVN Praha, Prague, Czech Republic; Toronto General Hospital, Toronto, Canada; AW Morrow Gastroenterology & Liver Center, Royal Prince Alfred Hospital, Camperdown, Australia; Hepatitis Research Clinic, Harborview Medical Center, Seattle, WA; Klinik & Poliklinik F. Innere Medizin, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany; Gilead Sciences, Durham, NC.

5/13/08

Reference
M Buti, S Hadziyannis, P Mathurin, and others. Tenofovir disoproxil fumarate (TDF) is highly active for treatment of chronic hepatitis B in subjects with cirrhosis. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.