title: Screening for hepatocellular carcinoma in chronic liver disease: a systematic review.
abstract: BACKGROUND
  Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear.
  
  
  OBJECTIVE
  To review the benefits and harms of HCC screening in patients with chronic liver disease.
  
  
  METHODS
  MEDLINE, PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors.
  
  
  METHODS
  English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals.
  
  
  METHODS
  Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria.
  
  
  RESULTS
  Of 13,801 citations, 22 studies met inclusion criteria. The overall strength of evidence on the effects of screening was very low. One large trial of patients with hepatitis B found decreased HCC mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI, 0.41 to 0.98]), but the study was limited by methodological flaws. Another trial in patients with hepatitis B found no survival benefit with periodic α-fetoprotein screening. In 18 observational studies, screened patients had earlier-stage HCC than clinically diagnosed patients, but lead- and length-time biases confounded the effects on mortality. Two trials found no survival differences between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals. Harms of screening were not well-studied.
  
  
  CONCLUSIONS
  Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials.
  
  
  CONCLUSIONS
  There is very-low-strength evidence about the effects of HCC screening on mortality in patients with chronic liver disease. Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain.
  
  
  BACKGROUND
  U.S. Department of Veterans Affairs Quality Enhancement Research Initiative.
authors.forename: Devan
authors.initials: D
authors.lastname: Kansagara
authors.forename: Joel
authors.initials: J
authors.lastname: Papak
authors.forename: Amirala S
authors.initials: AS
authors.lastname: Pasha
authors.forename: Maya
authors.initials: M
authors.lastname: O'Neil
authors.forename: Michele
authors.initials: M
authors.lastname: Freeman
authors.forename: Rose
authors.initials: R
authors.lastname: Relevo
authors.forename: Ana
authors.initials: A
authors.lastname: Quiñones
authors.forename: Makalapua
authors.initials: M
authors.lastname: Motu'apuaka
authors.forename: Janice H
authors.initials: JH
authors.lastname: Jou
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000175:diagnosis* / Q000401:mortality*; D002908:Chronic Disease; D055088:Early Detection of Cancer; D019317:Evidence-Based Medicine; D006801:Humans; D008107:Liver Diseases / Q000150:complications*; D008113:Liver Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000401:mortality*; D008403:Mass Screening; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic