title: Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and nucleos(t)ide analog-experienced chronic hepatitis B patients.
abstract: OBJECTIVE
  This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years of innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients.
  
  
  METHODS
  Tenofovir disoproxil fumarate-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed.
  
  
  RESULTS
  After 3 years of TDF therapy, 97.7%, 71%, and 45.5% NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion, respectively. Compared with NA-naïve patients, NA-experienced patients without drug resistance and infected with lamivudine/telbivudine-resistant mutants showed similar results. In contrast, patients previously infected with adefovir-resistant mutants and with a suboptimal entecavir response showed significantly lower rates of virological response and hepatitis B e antigen loss/seroconverion than NA-naïve patients. Mean estimated glomerular filtration rate markedly reduced within 12 months of TDF therapy; however, it did not decrease significantly during 12-36 months of treatment. Diabetes mellitus was an independent predictor of a ≥ 0.5 mg/dL increase above baseline in serum creatinine level, and age, hypertension, diabetes mellitus, and baseline creatinine level were independent factors for > 20% decline in estimated glomerular filtration rate from baseline. Liver stiffness measurements improved significantly, but bone mineral density did not change significantly during treatment. Hepatocellular carcinoma incidence was low at 36 months. Age of > 60 years, cirrhosis, a low baseline platelet count and a high α-fetoprotein level at 12 months were significant predictors of hepatocellular carcinoma development.
  
  
  CONCLUSIONS
  Tenofovir disoproxil fumarate is effective and safe for NA-naïve and NA-experienced CHB patients and should be used cautiously in patients with comorbidities because of a renal dysfunction risk.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsin-Ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Yen
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kwong-Ming
authors.initials: KM
authors.lastname: Kee
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Tseng
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005919:Glomerular Filtration Rate; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides; D009711:Nucleotides; D012189:Retrospective Studies; D000068698:Tenofovir / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides; D000068698:Tenofovir
keywords: bone mineral density; entecavir; hepatitis B virus; liver stiffness measures; tenofovir