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

Abstract

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 patientlevel 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 alphafetoprotein 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

Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis

“…Harms in the FP group were also likely mitigated by the quick resolution of the findings, with many patients simply undergoing a single CT or MRI, without need for a biopsy. Patients with indeterminate liver lesions (eg, LI-RADS 3 or 4 lesions) have an intermediate risk of developing HCC, [33] and some undergo prolonged, repeated imaging, which may result in increased psychological distress compared to others. Therefore, although psychological harms in our study were mild compared to other cancers, there may still be subgroups who experience greater psychological distress and for whom counseling or other interventions may be beneficial.…”

“…TPs were defined as the detection of HCC on follow-up testing within 1 year of the positive surveillance test; FP was defined as no HCC within 1 year of the positive test; and TN remained HCC free for at least 1 year after the negative screening result. A 1-year cutoff was selected to allow sufficient time for cancer adjudication, given longer periods can be required for patients with indeterminate nodules on diagnostic CT or MR imaging 22,32–34 . Although false-negative results may result in psychosocial harms, we did not anticipate having sufficient patients for this analysis.…”

Non-alcoholic fatty liver disease-related hepatocellular carcinoma

“…83 Patients with indeterminate liver nodules (LI-RADS 3 or LI-RADS 4) have an intermediate risk of HCC, between 35-65%, so typically warrant close follow-up imaging, with biopsies used in cases that would change immediate clinical management. [84][85][86] Patients without cirrhosis or high-risk HBV should undergo biopsy for histologic confirmation, as imaging features have insufficient accuracy. 49 Although a diagnosis of HCC can be made radiographically in most cases, approximately 10% of HCCs will have atypical imaging features (e.g., arterial phase hyperenhancement alone or delayed washout alone).…”

Diagnosis and management of indeterminate liver nodules in patients with cirrhosis

“…[2] In patients with LR-4 observations, multidisciplinary discussions regarding treatment implications can help decide optimal follow-up, including repeat imaging within 3 months or immediate biopsy. [2] A routine biopsy of every LR-4 observation is not recommended given the risk of bleeding, tumor seeding, and false negative results; however, a biopsy may be warranted depending on factors including the size of the T A B L E 1 Factors associated with the development of HCC in patients with ILNs [7] Patient observation, transplant eligibility, and tumor marker levels. For example, a biopsy could be important for patients in whom liver transplant exception points would be awarded (eg, patients with decompensated cirrhosis and LR-4 observation ≥ 2 cm in maximum diameter).…”

“…Beyond the risk of prevalent HCC, ILNs also carry a high but variable risk of incident HCC during follow-up, with the strongest risk factor for HCC being the type of ILN (LR-3 vs. LR-4 observation). A systematic review demonstrated that 11.1%–24.5% of patients with LR-3 observations develop HCC over time, compared to 30.9%–71.0% of LR-4 observations 7 . Most patients with LR-4 observations who develop HCC do so in the first 6 months of follow-up, highlighting that most HCC are prevalent.…”