Source: Hernia  |  Posted 8 years ago

Lamivudine can control viral replication in HBeAg-negative chronic hepatitis B patients who have relapsed, but viral resistance eventually develops, new research suggests.

Long-term use of lamivudine appears to be safe in patients with HBeAg-negative chronic hepatitis B, although the emergence of lamivudine-resistant hepatitis B virus (HBV) mutants is a concern.

In a previous study, Grazia Niro, MD, with the Hospital Casa Sollievo della Sofferenza IRCSS, San Giovanni Rotondo, Italy, and colleagues demonstrated that combining lamivudine with interferon could prevent the emergence of lamivudine-resistant mutations. In that study, no patient receiving combination therapy developed YMDD mutants during therapy, whereas 19% of patients treated with lamivudine alone experienced a virological breakthrough.

In the current study, the researchers evaluated the benefits of long-term re-treatment with lamivudine monotherapy in 36 HBeAg-negative chronic hepatitis B patients, 20 of whom relapsed after a previous course of lamivudine monotherapy and 16 who relapsed after combination therapy with lamivudine plus interferon.

The researchers conducted biochemical and virological tests every 3 months. They also sequenced the region coding for the YMDD amino acid motif at baseline and breakthrough.

The length of re-treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4%, and 48.6% at 6, 12 and 24 months, respectively.

By the second year, 62.5% and 40% in the lamivudine/interferon and lamivudine group, respectively were considered responders ([]P[] = .10). The 18 responders at month 24 were on therapy after 25 to 51 months of treatment. The researchers report that 14 maintained a response, 9 of them from the lamivudine/interferon group and five from the lamivudine group.

"For the first time, these results establish the benefit of re-treatment with lamivudine monotherapy for anti-HBe-positive patients," Dr. Niro and colleagues note.

They conclude that re-treatment with lamivudine can control viral replication, and the effect is maintained for the initial 12 months in two-thirds of patients, but the subsequent response declines due to the development of viral resistance.