Predictors of hepatocellular carcinoma in LR-M category lesions, a multi-institutional analysis.

Purpose: The Liver Imaging Reporting and Data System (LI-RADS, LR) provides a framework for diagnosing hepatocellular carcinoma (HCC, LR-5). However, not all HCCs meet LR-5 criteria and are instead categorized as LR-M, probably or definitely malignant but not specific for HCC, necessitating biopsy for diagnosis. The purpose is to identify factors associated with HCC in LR-M observations.

Methods: This is an IRB-approved, retrospective analysis of participants from 8 institutions that had a LR-M observation on CT or MRI with corresponding histopathologic diagnosis. Demographics and biochemical data were examined. Central review using the LI-RADS v2018 algorithm was performed. Kappa statistics defined inter-reader agreement. Random forest and logistic regression analyses generated a model for HCC diagnosis.

Results: 162 participants with 162 LR-M observations were included. 46% of observations (74/162) were HCC and 37% were cholangiocarcinoma (60/162). Two of 34 imaging features- observation size and intra-lesion iron- showed moderate to strong inter-reader agreement (Kappa ≥ 0.60) while the remainder showed weak or no agreement (Kappa < 0.60). Random forest analysis showed biochemical features to be more predictive of HCC than imaging features. Logistic regression analysis of a model based on INR and AFP provided a 72% sensitivity and 61% specificity for HCC by Youden's index and a 90% specificity threshold yielded 38% sensitivity, 75% positive predictive value, and 66% negative predictive value.

Conclusions: Our results show INR and AFP are associated with HCC in LR-M observations. A high-specificity threshold may assist in the non-invasive diagnosis of HCC in the appropriate setting. In certain at-risk patients with a LR-M observation on diagnostic imaging, serum AFP and INR maybe useful tools for the non-invasive diagnosis of HCC.