title: Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.
abstract: BACKGROUND
  Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.
  
  
  METHODS
  After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system).
  
  
  RESULTS
  Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug.
  
  
  CONCLUSIONS
  In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.
  
  
  BACKGROUND
  Gilead Sciences.
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, INSERM Unit CRB3, Clichy, France. patrick.marcellin@bjn.aphp.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: George
authors.initials: G
authors.lastname: Germanidis
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.forename: Raul
authors.initials: R
authors.lastname: Aguilar Schall
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bornstein
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Kitrinos
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D017751:Safety Management; D012720:Severity of Illness Index; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine