Clinical

Entecavir switch effective in lamivudine-resistant chronic hepatitis B

Last Updated: 2006-07-10 16:25:08 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - In patients with lamivudine-resistant chronic hepatitis B, switching to entecavir results in clinically significant histologic, virologic, serologic, and biochemical benefits, with a safety profile comparable to lamivudine, clinicians report in the June issue of Gastroenterology.

"The majority of chronic hepatitis B patients require long-term suppression of viral replication to prevent the development of cirrhosis, liver failure and liver cancer," first author Dr. Morris Sherman noted in comments to Reuters Health. When the virus becomes resistant to lamivudine, as often occurs, viral replication continues at levels approximately the same as before treatment was instituted.

Entecavir, a selective nucleoside analogue, "offers an effective treatment for such patients to maintain suppression of viral replication, with a low frequency of resistance," Dr. Sherman said.

Dr. Sherman and colleagues randomly assigned 286 hepatitis B e antigen-positive patients with persistence or recurrence of viremia on long-term lamivudine treatment or with documented lamivudine-resistance mutations to switch to entecavir (1 mg daily) or to continue lamivudine (100 mg daily) for at least 52 weeks.

They report that histologic improvement was seen in 55% of entecavir-treated patients (68 of 124) versus 28% of lamivudine-treated patients (32 of 116), a significant difference with a p value < 0.0001.

"Entecavir strongly suppressed HBV DNA levels," according to the team. At 48 weeks, the mean change from baseline was -5.11 log10 copies/mL in the entecavir arm compared with -0.48 log10 copies/mL in the lamivudine arm. Nineteen percent of entecavir-treated patients achieved HBV DNA below the limit of detection by PCR (300 copies/mL) versus only 1% of lamivudine-treated patients.

Virologic rebound due to the emergence of entecavir resistance was seen in 2 of 141 entecavir-treated patients and genotypic evidence of resistance was detected in 10 patients.

Entecavir was well tolerated, the authors say, with less than 1% of patients experiencing ALT flares during entecavir treatment. This finding confirms phase II data indicating that the risk of ALT flare is low in patients with lamivudine-resistant virus who switch directly to, or are maintained on, entecavir.

Based on this study and others, entecavir is a "welcome addition to the armamentarium" against chronic hepatitis B virus infection, Dr. Sherman said.

Gastroenterology 2006;130:2039-2049.