Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review

Liver Transpl. 2022 Dec;28(12):1865-1875. doi: 10.1002/lt.26562. Epub 2022 Sep 5.


Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.

Publication types

  • Systematic Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinoma, Hepatocellular* / diagnostic imaging
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / etiology
  • Contrast Media
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnostic imaging
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / pathology
  • Liver Transplantation*
  • Magnetic Resonance Imaging / methods
  • Male
  • Retrospective Studies
  • Sensitivity and Specificity


  • Contrast Media