title: Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection.
abstract: Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks).
  
  
  
  We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients.
  
  
  
  Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks).
  
  
  
  Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine ≥ 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336).
  
  
  
  Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.
authors.affiliation: Department of Hepatology, Hepatic and Digestive Diseases (CIBERehd), Hospital General Universitari Vall d'Hebron and Networked Biomedical Research Center, Pg. Vall d'Hebron, 119-129, 08035, Barcelona, Spain, mbuti@vhebron.net.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
authors.forename: Joerg
authors.initials: J
authors.lastname: Petersen
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.forename: Zahary
authors.initials: Z
authors.lastname: Krastev
authors.forename: Raul
authors.initials: R
authors.lastname: Aguilar Schall
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: Martins
authors.forename: Prista
authors.initials: P
authors.lastname: Charuworn
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Kitrinos
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D010757:Phosphorous Acids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D010757:Phosphorous Acids; D000225:Adenine