title: Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis.
abstract: OBJECTIVE
  Entecavir (ETV) is a potent inhibitor of viral replication in chronic hepatitis B and prolonged treatment may result in regression of fibrosis. The aim of this study was to investigate the effect of ETV on disease progression.
  
  
  METHODS
  In a multicentre cohort study, 372 ETV-treated patients were investigated. Clinical events were defined as development of hepatocellular carcinoma (HCC), hepatic decompensation or death. Virological response (VR) was defined as HBV DNA <80 IU/ml.
  
  
  RESULTS
  Patients were classified as having chronic hepatitis B without cirrhosis (n=274), compensated cirrhosis (n=89) and decompensated cirrhosis (n=9). The probability of VR was not influenced by severity of liver disease (p=0.62). During a median follow-up of 20 months (IQR 11-32), the probability of developing clinical events was higher for patients with cirrhosis (HR 15.41 (95% CI 3.42 to 69.54), p<0.001). VR was associated with a lower probability of disease progression (HR 0.29 (95% CI 0.08 to 1.00), p=0.05) which remained after correction for established risk factors such as age. The benefit of VR was only significant in patients with cirrhosis (HR 0.22 (95% CI 0.05 to 0.99), p=0.04) and remained after excluding decompensated patients (HR 0.15 (95% CI 0.03 to 0.81), p=0.03). A higher HBV DNA threshold of 2000 IU/ml was not associated with the probability of disease progression (HR 0.20 (95% CI 0.03 to 1.10), p=0.10).
  
  
  CONCLUSIONS
  VR to ETV is associated with a lower probability of disease progression in patients with cirrhosis, even after correction for possible baseline confounders. When using a threshold of 2000 IU/ml, the association between viral replication and disease progression was reduced, suggesting that complete viral suppression is essential for nucleoside/nucleotide analogue treatment, especially in patients with cirrhosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Roeland
authors.initials: R
authors.lastname: Zoutendijk
authors.forename: Jurrien G P
authors.initials: JG
authors.lastname: Reijnders
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.forename: David J
authors.initials: DJ
authors.lastname: Mutimer
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Petersen
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Sonneveld
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008113:Liver Neoplasms / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine