By Liz Highleyman

Entecavir and adefovir are a nucleoside and nucleotide analog, respectively, widely used for treatment of chronic hepatitis B virus (HBV) infection. Antiviral agents such as these have potent antiviral activity, but HBV often rebounds when therapy is discontinued and the virus can develop resistance that compromises long-term effectiveness.

As described in the February 22, 2011, online edition of Virology Journal, Pan Zhao from the Therapy and Research Center for Liver Failure in Beijing and colleagues conducted a meta-analysis to compare 48-week efficacy of the 2 drugs in hepatitis B "e" antigen (HBeAg) positive nucleoside/nucleotide-naive Asian chronic hepatitis B patients.

A previous meta-analysis was limited to English-language publications and did not classify patients according to region, the study authors noted as background. But research indicates that Asian hepatitis B patients -- who are often infected at birth in endemic regions -- have some characteristics that differ from western populations, such as less durability of HBeAg responses after stopping therapy.

The Chinese investigators searched medical literature databases (Pubmed, Embase, Wanfang Database, and China National Knowledge Infrastructure) for relevant studies comparing entecavir and adefovir published through November 30, 2010. They included randomized clinical trials that lasted 48 weeks and tested 0.5 mg/day entecavir and 10 mg/day adefovir. They excluded studies in which participants had hepatitis C, HIV, or other coinfections, hepatocellular carcinoma, or liver transplants.

The researchers evaluated rates of undetectable HBV DNA viral load, alanine aminotransferase (ALT) normalization, HBeAg clearance, and HBeAg seroconversion.

Results

	6 studies meeting the eligibility criteria (1 English, 5 Chinese) were included in the meta-analysis; 1 was an international study with a majority of Asian patients.
	In the combined analysis, significantly more patients taking entecavir achieved undetectable HBV DNA than those taking adefovir (65% vs 36%; relative risk 1.73).
	More people in the entecavir arms experienced ALT normalization compared with the adefovir arms (71% vs 56%; relative risk 1.25).
	However, there were no statistically significant differences between entecavir and adefovir recipients with regard to rates of HBeAg clearance (11% vs 13%; relative risk 0.77) or HBeAg seroconversion (6% vs 8%; relative risk 0.74).

Based on these findings, the investigators wrote, "Entecavir is superior to adefovir in decreasing serum HBV DNA and normalizing ALT but similar [to] adefovir in clearing HBeAg and encouraging HBeAg seroconversion" for HBeAg positive nucleoside/nucleotide-naive Asian patients with chronic hepatitis B.

While entecavir performed better overall, the authors concluded that, "Adefovir can be still used for first-line therapy in these patients."

Investigator affiliations: Therapy and Research Center for Liver Failure, Beijing 302 Hospital, Beijing, China; Science and Technology Division, Academy of Military Medical Science, Beijing, China.

3/29/11

Reference
P Zhao, W Liu, J Zhao, and Q Guan. Comparison of the 48-week efficacy between entecavir and adefovir in HBeAg-positive nucleos(t)ide-naive Asian patients with chronic hepatitis B: a meta-analysis. Virology Journal 8(1): 75 (free full text). February 22, 2011.