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HBV Rebounds After Stopping Entecavir, Switching to Interferon May Help


Most hepatitis B "e" antigen (HBeAg) negative chronic hepatitis B patients relapsed after stopping treatment with the antiviral drug entecavir (Baraclude), according to a report in the May 15 online edition of Gut. A related study found that switching from entecavir to pegylated interferon increased the likelihood of HBeAg seroconversion and hepatitis B surface antigen(HBsAg) lossin HBeAg positive patients.

Entecavir Discontinuation

Nucleoside/nucleotide analogs such as entecavir are effective in suppressing hepatitis B virus (HBV) replication, but viral load often rebounds after drug discontinuation.

Wai-Kay Seto from the University of Hong Kong and colleagues evaluated outcomes among 184 HBeAg negative Asian patients who stopped taking entecavir after 2 or more years, in accordance with the guidelines of the Asia-Pacific Association for the Study of the Liver.

Two-thirds of study participants were men and the mean age was 54 years. They had undetectable HBV DNA viral load on at least 3 tests done 6 months apart before entecavir discontinuation. They restarted entecavir if they experienced viral relapse with HBV DNA >2000 IU/mL.


  • The cumulative rates of viral relapse were 74% and 91%, respectively, at 24 and 48 weeks after stopping entecavir.
  • The median HBV DNA level at the time of relapse was 11,000 IU/mL.
  • 26% of patients had elevated alanine aminotransferase (ALT) indicating active liver inflammation.
  • None of the patients experienced hepatitis B surface antigen (HBsAg) clearance.

"Entecavir cessation in Asian HBeAg negative [chronic hepatitis B] resulted in high rates of virologic relapse, suggesting [nucleoside/nucleotide] analogue therapy should be continued indefinitely until the recognized treatment endpoint of HBsAg seroclearance," the study authors concluded.

Switch to Pegylated Interferon

In the second study, described in the June 7 advance edition of the Journal of Hepatology, Qin Ning fromHuazhong University of Science and Technology in Wuhan, China, and fellow investigators with the OSST Trial looked at outcomes among hepatitis B patients who switched from entecavir to pegylated interferon.

This study included 197 people with HBeAg positive chronic hepatitis B who had taken entecavir for 9 to 36 months and had HBV viral load <1000 copies/mL. They were randomly assigned to switch to weekly injections of pegylated interferon alfa-2a or to continue on 0.5 mg/day entecavir for 48 weeks.


  • Participants who switched to pegylated interferon were significantly more likely to experience HBeAg seroconversion at 48 weeks compared with those who continued taking entecavir (15% vs 6%) in a modified intent-to-treat analysis.
  • Only patients receiving pegylated interferon achieved HBsAg loss, though this occurred in only 9%.
  • Among pegylated interferon recipients with HBeAg loss and HBsAg <1500 IU/mL at randomization, 33% achieved HBeAg seroconversion and 22% had HBsAg loss.
  • The decline in HBsAg during early treatment predicted response at week 48, with the best responses seen among patients with HBsAg <200 IU/mL at week 12 (67% HBeAg seroconversion and 78% HBsAg loss).

"For patients who achieve virological suppression with entecavir, switching to a finite course of [pegylated interferon] alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss," the researchers concluded. "A response-guided approach may identify patients with the greatest chance of success."



WK Seto, AJ Hui, VW Wong, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut. May 15,2014 (Epub ahead of print).

Q Ning, M Han, Y Sun, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial). Journal of Hepatology. June 7, 2014 (Epub ahead of print).