title: Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B: results of a multicentre, prospective study.
abstract: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients.
  
  
  
  In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks.
  
  
  
  A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2-6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11-6.73) log10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log10 IU/ml and 2.38 log10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients.
  
  
  
  In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Liver Cirrhosis Clinical Research Center, Seoul, Korea.|Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Korea.
authors.forename: Chang Wook
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Liver Cirrhosis Clinical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Kyu Sik
authors.initials: KS
authors.lastname: Jung
authors.affiliation: Liver Cirrhosis Clinical Research Center, Seoul, Korea.|Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Korea.
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Liver Cirrhosis Clinical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Liver Cirrhosis Clinical Research Center, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D056910:Republic of Korea; D000068698:Tenofovir / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir
keywords: chronic hepatitis B; combination therapy; entecavir; multidrug resistant; tenofovir