Half of HBeAg Negative Chronic Hepatitis B Patients Maintain Response up to 5 Years after Stopping Long-term Adefovir (Hepsera)

By Liz Highleyman

Several nucleoside/nucleotide analogs are effective against hepatitis B virus (HBV), but the virus mutates rapidly and resistance is a barrier to successful long-term treatment.

Adefovir (Hepsera)

In a study presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen, S. Hadziyannis from Henry Dunant Hospital in Athens, Greece, and colleagues evaluated long-term clinical, biochemical, virological, and serological outcomes in 33 hepatitis B "e" antigen (HBeAg) negative chronic hepatitis B patients who discontinued adefovir (Hepsera) with undetectable HBV DNA after 4-5 years of use. Most participants (about 80%) were men and the mean age was 50 years. About one-third had taken adefovir for 4 years and about two-thirds had done so for 5 years.

Serum samples were obtained every month for 6 months, then every 3 months for the remainder of the 5-year follow-up period. Liver enzyme levels, hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) status, and HBV DNA levels were assessed. Needle liver biopsies were performed at baseline, at 1 year after starting adefovir, at the end of treatment, and during follow-up. Host and viral variables, including HBsAg expression and HBV replication in the liver, were evaluated as possible predictors of sustained response, HBsAg clearance, and HBV relapse.

Participants restarted adefovir if they experienced persistent biochemical relapse (ALT > 1.5 x upper limit of normal [ULN]) for 3 consecutive months or a severe ALT flare (> 10 x ULN).

Results

During the first 3 months after stopping adefovir, serum HBV DNA again became detectable in all patients, but this steadily decreased over time.

ALT flares were also common during this period.

18 of the 33 patients (55%) had sustained biochemical and virological remission by their final evaluation at year 5.

15 of 33 (45%) experienced persistent biochemical and virological relapse resulting in re-initiation of therapy.

6% of sustained biochemical responders had HBV RNA < 1000 copies/mL at 1 month, 44% did so at 24 months, and 67% did so at 48 months.

10 of 18 (55%) sustained responders -- or 27% of the entire cohort -- achieved HBsAg loss.

6 of 18 (33%) experienced HBsAg seroconversion.

Relapsing patients showed no evidence of liver decompensation regardless of ALT levels or HBV DNA flares.

The pattern of HBsAg expression on hepatocytes in the liver and achieving at least a 2.5 log decrease in total and cccDNA during treatment were associated with HBsAg clearance.

In the fifth year following discontinuation of long-term adefovir treatment in HBeAg negative chronic hepatitis B patients, 55% "have remained in sustained remission" and more than half have achieved "the closest to cure outcome of HBsAg loss," the study investigators concluded.

"Early post-treatment increases in ALT activity and/or re-detectability of serum HBV DNA are usually short-lived," the researchers continued, recommending that relapsing patients should be followed for a while to see if they experience spontaneous resolution rather than immediately restarting therapy.

Hepatology, Henry Dunant Hospital and Molecular Biology Laboratory of the Liver Unit, Athens University at the Evgenidion Hospital, Athens, Greece.

5/05/09

Reference
S Hadziyannis, V Sevastianos, and I Rapti. Outcome of HBeAg-negative chronic hepatitis B (CHB) 5 years after discontinuation of long term adefovir dipivoxil (ADV) treatment. Program and abstracts of the 44th Annual Meeting of the European Association for the Study of the Liver; April 22-26, 2009; Copenhagen, Denmark. Abstract 18.

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