Entecavir Associated With Later Virological Relapse Than Tenofovir

Hepatitis B virions
Hepatitis B virions
Investigators assessed factors associated with the time of virological relapse after discontinuing therapy with tenofovir or entecavir.

A comparison of the nucleos(t)ide analogues tenofovir and entecavir revealed that virological relapse occurred much later for people with a chronic hepatitis B virus (HBV) infection who were e antigen negative after stopping entecavir, according to findings published in The Journal of Infectious Diseases.

A total of 220 people aged 18 to 65 years were enrolled from the Asian-Pacific region; participants represented 38 centers across 7 countries. Each participant received treatment with nucleos(t)ide analogues for at least 2 years. All participants had a chronic HBV infection, were e antigen negative, and had been producing hepatitis B e antibodies for at least 1 year before study screening. The participants were divided into groups: those taking entecavir (n=154) and those taking tenofovir disoproxil (n=66).

Therapy with each nucleos(t)ide analogue was stopped after 24 weeks. “Follow-up was until 24 weeks or [nucleos(t)ide analogue] retreatment.” During the first 8 weeks, participants were followed every 2 weeks. After the 8-week mark, participants were followed every 4 weeks. Investigators noted the major end point of the study was “virological remission (HBV-DNA levels <40 IU/mL) until 24 weeks after stopping [nucleos(t)ide analogues].”

Virological relapse (HBV DNA > 2,000 IU/mL) occurred in 24.5% of the participants (n=54) until week 12 and 57.3% (n=126) until week 24. Some participants (32.7%; n=72) experienced a later relapse between week 16 and week 24. Of the participants treated with tenofovir, 71% (n=47) had virological relapse until week 12. Of those treated with entecavir, 4.5% had virological relapse (n=7) in the same period (P<.0001). Researchers found that 6 weeks after ceasing tenofovir marked the median time to virological relapse; 24 weeks was the median time for relapse after discontinuing entecavir (P< .0001).

Study limitations include a homogenous pool of participants. Researchers also note that there were no assessments for nucleos(t)ide analogue resistance in the study, nor was virological relapse “confirmed immediately by a repeated test.”

According to study authors, “this is the largest prospective study showing that the type of nucleos(t)ide analogue affects relapse after cessation of therapy. This is an important finding for clinical practice as well as for future studies addressing whether treatment discontinuation has an impact on functional cure of HBV infection.” The investigators also note that given the study findings, there may be more to the choice of nucleos(t)ide analogues than “lamivudine resistance, costs, or certain comorbidities.” They recommended “close follow-up even more than 3 months after treatment discontinuation” for people treated with entecavir.

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This study was supported by ABIVAX, a biotechnology company in Paris, France. Please refer to the reference for a complete list of authors’ disclosures.


Höner zu Siederdissen C, Hui AJ, Sukeepaisarnjaroen W, et al. Contrasting timing of virological relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients [published online June 9, 2018]. J Infect Dis. doi:10.1093/infdis/jiy350