Screening for hepatocellular carcinoma in chronic liver disease: a systematic review

Ann Intern Med. 2014 Aug 19;161(4):261-9. doi: 10.7326/M14-0558.


Background: Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear.

Purpose: To review the benefits and harms of HCC screening in patients with chronic liver disease.

Data sources: MEDLINE, PsycINFO, and from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors.

Study selection: English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals.

Data extraction: Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria.

Data synthesis: 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.

Limitations: Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials.

Conclusion: 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.

Primary funding source: U.S. Department of Veterans Affairs Quality Enhancement Research Initiative.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / mortality*
  • Chronic Disease
  • Early Detection of Cancer*
  • Evidence-Based Medicine
  • Humans
  • Liver Diseases / complications*
  • Liver Neoplasms / complications
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / mortality*
  • Mass Screening*
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic