title: Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B.
abstract: BACKGROUND
  Efficacy trials have shown that antiviral therapy improves the outcomes of patients with chronic hepatitis B virus (HBV) infection. However, prospective data regarding the effect of antiviral therapy on the incidence of hepatocellular carcinoma (HCC), especially among patients without cirrhosis, are limited. The authors examined the impact of tenofovir disoproxil fumarate (TDF) on the incidence of HCC using a validated prediction model.
  
  
  METHODS
  The incidence of HCC in patients treated with TDF was obtained in the pivotal TDF registration studies after 384 weeks of follow-up. The predicted risk of HCC in individual patients was calculated using the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model, which estimates HCC incidence for up to 10 years based on age, sex, alanine aminotransferase level, hepatitis B e antigen status, and HBV-DNA. Standardized incidence ratios (SIRs) were calculated comparing the observed and predicted numbers of HCC cases in the study cohort.
  
  
  RESULTS
  Among 634 patients with evaluable baseline biopsies, 152 had cirrhosis (Ishak fibrosis score of 5 or 6) and 482 did not. During the 384 weeks of study, 14 cases of HCC were reported, with 4 occurring within the first year. The incidence of HCC was 0.37% per year in the study as a whole (0.28% among patients without cirrhosis and 0.65% among patients with cirrhosis). Among patients without cirrhosis, the observed incidence of HCC was significantly lower than predicted (SIR, 0.40; 95% confidence interval, 0.199-0.795). The last HCC case in a patient with cirrhosis occurred around week 192 with an SIR of 0.51 (95% confidence interval, 0.231-1.144) reported at week 384.
  
  
  CONCLUSIONS
  Based on the REACH-B risk calculator, long-term therapy with TDF was associated with a reduced incidence of HCC among patients without cirrhosis who met treatment criteria.
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California.
authors.forename: W Ray
authors.initials: WR
authors.lastname: Kim
authors.affiliation: Divisions of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, California.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.affiliation: Section of Hepatology, Division of Gastroenterology and Rheumatology, Department of Internal Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Aguilar Schall
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Leland J
authors.initials: LJ
authors.lastname: Yee
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Phillip V
authors.initials: PV
authors.lastname: Dinh
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.affiliation: Gilead Sciences Inc, Foster City, California.
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: Martins
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Terry M
authors.initials: TM
authors.lastname: Therneau
authors.affiliation: Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, New York.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobson
authors.affiliation: Department of Gastroenterology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: Department of Gastroenterology, Uludag University Medical School, Bursa, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.affiliation: Liver Unit, University Hospital Vall d'Hebron and Institute Ciberehd Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: Hepatology Service, Beaujon Hospital, Paris-Diderot University and INSERM CRI/UMR 1149, Viral Hepatitis Research Centre, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D000068698:Tenofovir / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000068698:Tenofovir
keywords: REACH-B; antiviral therapy; chronic hepatitis B; fumarate; hepatocellular carcinoma; tenofovir disoproxil