Heathcote, E. JennyMarcellin, PatrickButi, MariaGane, EdwardDe Man, Robert A.Krastev, ZaharyGermanidis, GeorgeLee, Samuel S.Flisiak, RobertKaita, KellyManns, MichaelKotzev, IskrenTchernev, KonstantinBuggisch, PeterWeilert, FrankKurdas, Oya OvuncShiffman, Mitchell L.Trinh, HuySnow-Lampart, AndreaBorroto, Katyna EsodaMondou, ElsaAnderson, JaneSorbel, JeffRousseau, Franck2022-10-062022-10-062011-01Heathcote, E. J. vd. (2011). "Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B". Gastroenterology, 140(1), 132-143.0016-50851528-0012https://doi.org/10.1053/j.gastro.2010.10.011https://pubmed.ncbi.nlm.nih.gov/20955704/http://hdl.handle.net/11452/28987BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg+ or HBeAg-). METHODS: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). RESULTS: At week 144, 87% of HBeAg- and 72% of HBeAg+ patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg- and 71% of the HBeAg+ patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg+ patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years. CONCLUSIONS: TDF was safe and effective in the long-term management of HBeAg+ and HBeAg- patients with chronic hepatitis B.eninfo:eu-repo/semantics/closedAccessGastroenterology & hepatologyLiver diseaseVirologyDrug resistanceViral replicationNucleotideHbeag-positive patientsTerm-follow-upSerum hbsagPeginterferon alpha-2aAdefovir dipivoxilSustained responseNegative patientsNatural-historyVirus-infectionDna levelArticle0002855032000292-s2.0-78650477355132143140120955704Gastroenterology & hepatologyHepatitis B E Antigen; Entecavir; Liver Cell CarcinomaAdefovir dipivoxilAlanine aminotransferaseDNA polymeraseEmtricitabineLamivudineTenofovir disoproxilVirus DNAAdd on therapyAdultAlanine aminotransferase blood levelAmino acid substitutionArticleAttention disturbanceChronic hepatitisChronic hepatitis bControlled studyCreatinine blood levelDiarrheaDizzinessDouble blind procedureDrug efficacyDrug induced headacheDrug safetyFatigueFemaleHepatitis BHepatitis B virusHumanInfluenzaLiposarcomaLiver biopsyLiver cell carcinomaMajor clinical studyMaleMonotherapyMutationNauseaPriority journalRandomized controlled trialRhinopharyngitisSeptic shockSide effectSingle drug doseTreatment withdrawalUpper abdominal pain