Long-term outcomes of indeterminate focal hepatic observations less than 20 mm followed up with gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI)

Abstract

Background: Indeterminate hepatic observations classified as Liver Imaging Reporting and Data System (LI-RADS) category 3 (LR-3) exhibit uncertain malignant potential and pose a diagnostic challenge during hepatocellular carcinoma (HCC) surveillance. Although most LR-3 observations remain stable, recent studies have reported variable progression rates to HCC. The purpose of the present study was to investigate and assess the clinical outcomes and progression-associated factors of LR-3 observations less than 20 mm in high-risk patients, on follow-up with serial gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI).

Methods: A retrospective review was conducted on 125 patients with hepatitis B virus (HBV)-related cirrhosis who underwent Gd-EOB-MRI examinations at index and during follow-up. A total of 149 untreated LR-3 observations less than 20 mm in size were included in the study. Stepwise multivariate Cox proportional hazards model analysis was performed to identify the predictive risk factors for progression (upgraded to LR-4 or LR-5), including patient demographics and LI-RADS imaging features. Overall cumulative risk for progression was calculated using the Kaplan-Meier method, and significant predictive risk factors were compared using the log-rank test.

Results: Over a median follow-up period of 18.3 months (range, 2.7-78.5 months), the overall cumulative risk of progression for LR-3 observations was 41.6% (62/149) and was 1.3%, 9.5%, 17.3%, and 37.3% at 3, 6, 12, and 24 months, respectively. The multivariate analysis revealed three significant independent predictors of progression: non-rim arterial phase hyperenhancement (APHE) [hazard ratio (HR) =2.19; P=0.005], subthreshold growth (HR =2.78; P=0.001), and mild-to-moderate T2 hyperintensity (HR =5.25; P<0.001). LR-3 observations with non-rim APHE or mild-to-moderate T2 hyperintensity showed a significantly higher cumulative risk of progression (53.3% vs. 33.7% and 50.0% vs. 28.8%, respectively; both P<0.001), as well as a shorter median interval to LR category upgrade (14.7 vs. 18.9 months and 15.1 vs. 26.5 months, respectively; both P<0.001), compared to those without these features.

Conclusions: Non-rim APHE, subthreshold growth, and mild-to-moderate T2 hyperintensity were significantly associated with an increased risk of progression among high-risk patients with LR-3 observations.. In particular, the presence of non-rim APHE or mild-to-moderate T2 hyperintensity was linked to both a higher cumulative incidence of progression and a shorter median interval to LR category upgrade.

Keywords: Hepatocellular carcinoma (HCC); Liver Imaging Reporting and Data System (LI-RADS); Liver Imaging Reporting and Data System category 3 (LR-3); follow-up; gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI).

Figure 1

Flowchart of the study population. The flowchart illustrates the study selection process on the basis of LI-RADS v2018 categorization of observations included in this study. There is an overlap of some patients who had multiple LR-3 observations during follow-up. Specifically, these patients had both progressing and non-progressing nodules, and thus were included in both the progression group and non-progression based on lesion-level analysis. Gd-EOB-MRI, gadoxetic acid-enhanced magnetic resonance imaging; HCC, hepatocellular carcinoma; LI-RADS, Liver Imaging Reporting and Data System; LR-3, Liver Imaging Reporting and Data System category 3; MRI, magnetic resonance imaging.

Figure 2

Diagram illustrating the changes in LI-RADS v2018 categories during follow-up (from index to final examination) for LR-3 observations included in this study. LI-RADS, Liver Imaging Reporting and Data System; LR-1, Liver Imaging Reporting and Data System category 1; LR-2, Liver Imaging Reporting and Data System category 2; LR-3, Liver Imaging Reporting and Data System category 3; LR-4, Liver Imaging Reporting and Data System category 4; LR-5, Liver Imaging Reporting and Data System category 5.

Figure 3

The LR-3 observation progressed to LR-5 based on LI-RADS v2018 during follow-up. (A-C) The index Gd-EOB-MRI showed an 8-mm non-rim APHE on the late arterial phase in hepatic segment II/III (A, arrow), without non-peripheral washout and enhancing capsule on the portal venous phase (B, arrow) or transitional phase (not shown), and hypointensity on HBP (C, arrow). The observation was initially categorized as LR-3. (D-F) After a 5-month Gd-EOB-MRI follow-up, the observation increased from 8 to 15 mm with non-rim APHE (D, arrow), with non-peripheral washout on the portal venous phase (E, arrow) and hypointensity on HBP (F, arrow). Due to the combination of imaging features (10–19 mm, non-rim APHE, non-peripheral washout, and threshold growth), the observation was consequently categorized as LR-5. APHE, arterial phase hyperenhancement; Gd-EOB-MRI, gadoxetic acid-enhanced magnetic resonance imaging; HBP, hepatobiliary phase; LI-RADS, Liver Imaging Reporting and Data System; LR-3, Liver Imaging Reporting and Data System category 3; LR-5, Liver Imaging Reporting and Data System category 5.

Figure 4

The LR-3 observation progressed to LR-5 based on LI-RADS v2018 during follow-up. (A-C) Baseline Gd-EOB-MRI showed a 15-mm observation without non-rim APHE on the late arterial phase (A, arrow), without non-peripheral washout on the portal venous phase (B, arrow) or transitional phase (not shown), with hypointensity on HBP in hepatic segment V/VI (C, arrow). The observation was initially categorized as LR-3. (D-F) After a 17-month Gd-EOB-MRI follow-up, the observation increased from 15 to 19 mm with non-rim APHE (D, arrow), with non-peripheral washout on the portal venous phase (E, arrow) and hypointensity on HBP (F, arrow). Due to the combination of imaging features (10–19 mm, non-rim APHE, non-peripheral washout, and subthreshold growth), the observation was consequently categorized as LR-5. APHE, arterial phase hyperenhancement; Gd-EOB-MRI, gadoxetic acid-enhanced magnetic resonance imaging; HBP, hepatobiliary phase; LI-RADS, Liver Imaging Reporting and Data System; LR-3, Liver Imaging Reporting and Data System category 3; LR-5, Liver Imaging Reporting and Data System category 5.

Figure 5

Kaplan-Meier analysis of the cumulative incidence of progression. (A) Overall cumulative incidence of progression of LR-3 observations. (B) Comparison of observations with or without non-rim APHE. (C) Comparison of observations with or without mild-to-moderate T2 hyperintensity. (D) Comparison of observations with or without subthreshold growth. The cumulative risk rates were significantly higher in the presence of non-rim APHE (log-rank test P<0.001) or mild-to-moderate T2 hyperintensity (log-rank test P<0.001) but were not significantly affected by the presence of subthreshold growth (log-rank test P=0.056). APHE, arterial phase hyperenhancement; LR-3, Liver Imaging Reporting and Data System category 3; LR-4, Liver Imaging Reporting and Data System category 4; LR-5, Liver Imaging Reporting and Data System category 5.