title: Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial.
abstract: BACKGROUND
  Telbivudine has been suggested to induce hepatitis B surface antigen (HBsAg) decline to the similar degree as pegylated interferon. We aimed to investigate whether telbivudine could further decrease HBsAg titer in patients who maintain undetectable serum hepatitis B virus (HBV) DNA after initial entecavir treatment.
  
  
  METHODS
  In this open-label trial, patients who had serum HBsAg and HBV DNA levels ≥1,000 IU/mL and <60 IU/mL, respectively, following entecavir (0.5 mg/day) treatment for HBeAg-positive chronic hepatitis B were randomized to either switch treatment to telbivudine (600 mg/day, n = 47) or continue entecavir (n = 50) for 48 weeks.
  
  
  RESULTS
  The baseline characteristics were comparable between groups including HBsAg levels (median, 3.41 log10IU/mL). All patients had undetectable HBV DNA and normal alanine aminotransferase level. At week 48, the mean change in serum HBsAg levels was not significantly different between the telbivudine and entecavir groups (-0.03 log10IU/mL vs. -0.05 log10IU/mL; P = 0.57). No patient experienced HBsAg seroclearance or HBsAg decline >0.5 log10IU/mL. Eleven patients (23.4%) in the telbivudine group, but none in the entecavir group, experienced virologic breakthrough (P < 0.001). Seven patients (14.9%) exhibited genotypic resistance mutations (M204I +/- L180M) during the virologic breakthrough.
  
  
  CONCLUSIONS
  Sequential therapy with entecavir followed by telbivudine resulted in a high rate of virologic breakthrough and drug-resistance without any beneficial effect on HBsAg decline. These results do not support the use of low genetic barrier drugs as a switch treatment strategy in patients who achieve virologic response with high genetic barrier drugs.
  
  
  BACKGROUND
  NCT01595685 (date of trial registration: May 8, 2012).
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. limys@amc.seoul.kr.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.affiliation: Health Screening and Promotion Center, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Gi-Ae
authors.initials: GA
authors.lastname: Kim
authors.affiliation: Department of Applied Statistics, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Seong-Bong
authors.initials: SB
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Jeong
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Danbi
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Yung Sang
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077712:Telbivudine; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000077712:Telbivudine; C413685:entecavir; D006147:Guanine; D013936:Thymidine
keywords: HBsAg; Hepatitis B surface antigen; Resistance; Virologic breakthrough; Virologic response