Cheaper Hepatitis B Treatment Causes Long-Term Drug Resistance

Patients treated for chronic HBV with a more-expensive drug, entecavir, followed by maintenance with a cheaper alternative, lamivudine (LAM), developed drug resistance over a two-year period.

AsianScientist (Mar. 31, 2011) – Patients treated for chronic hepatitis B virus (HBV) infection with a more-expensive drug, entecavir, followed by maintenance with a cheaper alternative, lamivudine (LAM), developed drug resistance over a two-year period.

Patients enrolled in this study showed a virologic rebound rate of 24 percent and a resistance rate of 12 percent. Patients remaining on entacavir throughout the two-year study, however, had undetactable HBV DNA.

The World Health Organization (WHO) estimates that more than 2 billion people worldwide have been infected with HBV; roughly 360 million of these cases are chronic infections that could lead to liver cirrhosis and liver cancer.

LAM was the first oral antiviral agent available to treat chronic HBV infection. Entecavir was later shown to be superior to LAM in reducing HBV DNA, but more costly to use over the long-term.

Published in the April issue of Hepatology, a team led by Prof. Man-Fung Yuen from the University of Hong Kong investigated whether initial HBV DNA suppression by the more potent antiviral agent, entecavir, could be maintained by switching to LAM, the less potent and lower-cost antiviral.

“Most patients with chronic HBV require long-term antiviral treatment and some patients opt to start with LAM therapy for cost-saving reasons. Our aim was to determine the efficacy and drug-resistance profile of switching to LAM after initial entecavir treatment,” said Dr. Fung.

All 50 patients with chronic HBV in the study were initially treated with entecavir. Half the patients continued to receive 0.5 mg of entecavir daily, while the other half switched to 100 mg LAM daily.

Routine liver biochemistry, hepatitis B serological tests and HBV DNA measurements showed that all patients continuing with entecavir had undetectable HBV DNA; 24 percent of those who switched to LAM experienced virological rebound, with increasing viral loads over time. Additionally, three patients (12 percent) became resistant to LAM.

Hence, prior HBV DNA suppression with entecavir did not offer any significant advantage to patients who switched to LAM, due to the development of resistance.

The full paper can be found at: Fung J. et al. (2011) Randomized Trial of Lamivudine Versus Entecavir in Entecavir-Treated Patients with Undetectable HBV DNA: Outcome At 2 Years.

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Source: Wiley-Blackwell.
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