Patients with hepatitis B who did not respond to lamivudine therapy had a better virological response after switching to entecavir for a year. Continuing the drug for an additional year led to even more clinical improvement without significant side effects, according to a new study in the July issue of Hepatology.
Chronic hepatitis B is the tenth leading cause of death worldwide. Infected patients are at high risk of developing serious liver diseases such as cirrhosis and liver cancer, especially if they have high levels of HBV DNA in their blood. Lamivudine is one treatment for HBV, however the virus commonly becomes resistant to it and leads to disease progression. Adefovir dipivoxil is another treatment option, however virologic suppression is not optimal. A third drug, Entecavir, has been shown to be a safe and effective treatment for patients who don't respond to lamivudine.
Researchers led by Morris Sherman of Toronto General Hospital, studied 286 patients taking part in a double-blind, double-dummy, randomized, controlled trial comparing the safety and efficacy of entecavir (1 mg/day) to lamivudine (100 mg/day). The results of the first year of this trial were previously reported. 57 percent of patients taking entecavir, compared to five percent of those taking lamivudine were classified as virologic responders, and were offered continued therapy for an additional year. The researchers then assessed the efficacy, safety and resistance profile of entecavir through 96 weeks of treatment.
"The year-two results demonstrated that patients continue to experience clinical benefit with entecavir therapy beyond one year, while the safety profile remained stable," the authors report. The additional year of treatment increased the proportion of patients with HBV DNA <300 copies/mL from 21 percent to 40 percent.
Analysis showed that seven patients in the total entecavir-treated cohort had baseline resistance to the drug. Another 10 became resistant in year one, and seven more in year two. Virologic breakthrough lagged behind the development of resistance.
"In summary, a second year of entecavir treatment in lamivudine-refractory patients with HbeAg-positive chronic hepatitis B resulted in continued virologic, serologic and biochemical improvement and a safety profile that was comparable with the first year of therapy," they conclude. "A longer duration of treatment and continued treatment of patients with HbeAg loss may lead to higher rates of virologic response and seroconversion in lamivudine-refractory chronic hepatitis B patients."
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