LAUSR

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.