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 ClinicalTrials.gov 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.
