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Adding Adefovir Works Better than Entecavir Monotherapy for Lamivudine-resistant Hepatitis B Patients

Addition of adefovir (Hepsera) to lamivudine (Epivir-HBV) proved to be a better "rescue therapy" strategy for patients with lamivudine-resistant hepatitis B virus (HBV) than switching to entecavir (Baraclude) monotherapy, according to a South Korean study published in the August 2010 Journal of Gastroenterology and Hepatology.

Lamivudine, the first oral nucleoside analog used to treat chronic hepatitis B, has potent antiviral activity, but HBV develops resistance mutations relatively easily and rapidly, compromising the effectiveness of long-term therapy. Combining drugs makes it more difficult for the virus to mutate enough to overcome them.

Hong Joo Kim and colleagues from Sungkyunkwan University in Seoul conducted a study to compare strategies for "rescue therapy" for individuals who developed resistance to lamivudine.

The analysis included 104 chronic hepatitis B patients who were failing lamivudine treatment, randomly allocated into 3 treatment arms:

  • Group 1 (n = 24): switch from lamivudine monotherapy to 1.0 mg once-daily entecavir monotherapy;
  • Group 2 (n = 44): switch from lamivudine monotherapy to 10 mg once-daily adefovir monotherapy;
  • Group 3 (n = 36): stay on lamivudine and add 10 mg once-daily adefovir.


  • After 6 months of rescue therapy, patients receiving lamivudine/adefovir add-on therapy were significantly more likely to achieve undetectable HBV DNA (< 300 copies/mL) than those in either monotherapy arm (P = 0.003):
  • Entecavir monotherapy: 33.3%;
  • Adefovir monotherapy: 27.3%;
  • Lamivudine/adefovir combination: 68.6%.
  • The decrease in HBV DNA viral load was significantly larger in the lamivudine/adefovir add-on group compared with the entecavir monotherapy group.
  • Viral breakthrough and genotypic resistance were significantly more common in the monotherapy groups, and not seen in the combination therapy arm, 24 months after starting antiviral treatment (P < 0.01):
  • Entecavir monotherapy: 6 patients (25.0%);
  • Adefovir monotherapy: 6 patients (13.6%);
  • Lamivudine/adefovir combination: no cases.
  • The cumulative rate of hepatitis B "e" antigen (HBeAg) seroconversion was significantly higher in the adefovir/lamivudine add-on and adefovir monotherapy groups compared with the entecavir monotherapy group (P = 0.022).
  • Alanine aminotransferase (ALT) normalization was more likely in the entecavir monotherapy and adefovir/lamivudine add-on arms compared with the adefovir monotherapy arm (75.0%, 74.3%, and 65.9%, respectively), but the difference did not reach statistical significance.

Based on these findings, the researchers concluded, "Adefovir add-on treatment in patients with lamivudine-resistant chronic hepatitis B suppresses HBV replication more effectively than entecavir or adefovir monotherapy."

Additionally, they continued, "no genotypic resistance was detected in the adefovir add-on group."

Investigator affiliation: Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea.



HJ Kim, JH Park, DI Park, and others. Rescue therapy for lamivudine-resistant chronic hepatitis B: comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy. Journal of Gastroenterology and Hepatology 25(8): 1374-1380 (Abstract). August 2010.