Multivariate analysis showed that these two factors were significantly AUY-922 price associated with HCC occurrence: the presence of coexistent HCC (hazard ratio [HR], 4.975; 95% confidence interval [CI], 1.729–14.316; P = 0.003) and AFP > 20 ng/mL (HR, 4.104; 95% CI, 1.621–10.392; P = 0.003). The median observation time between HCC detection and the last imaging session was 4.0 months (2.3–6.3). Fourteen lesions were diagnosed

as HCCs developed from PIELs during the study period (Table 3, Figs 3 and 4). Diagnosis of HCC was made by CEUS, CT, and MRI in 10, by CT and MRI in two, by CEUS and CT in one, by CEUS and MRI in one. All of them had a PIEL diameter larger than 10 mm at baseline, and 14 mm was identified as the best cut-off value of the diameter of PIEL to predict HCC occurrence. Univariate analysis showed PIEL > 14 mm (P < 0.001) and AFP > 20 ng/mL (P < 0.001) were significant risk factors for HCC occurrence from PIELs. Cumulative HCC occurrence rates

were significantly higher in patients with PIEL > 14 mm (n = 24; 23.5% at 1 year, 46.3% at 3 years) than in patients with PIEL ≤ 14 mm (n = 63; 1.9% at 1 year, 14.6% at 3 years; P < 0.001) (Fig. 2). Among the other clinical parameters analyzed, AFP was the only factor that showed a significant relationship with the HCC occurrence, that is, 21.7% at 1 year and 62.7% at 3 years in patients with AFP > 20 ng/mL (n = 27) versus 2.0% at 1 year and 9.4% at 3 years (P < 0.001) in patients with AFP ≤ 20 ng/mL (n = 60) (Fig. 2). Multivariate analysis showed that these two factors were Dabrafenib molecular weight significantly associated with HCC occurrence (i.e. PIEL > 14 mm: HR, 6.780; 95% CI, 2.060–22.32; P = 0.002; and AFP > 20 ng/mL: HR, 4.892; 95% CI, 1.559–15.350; P = 0.007). There was no significant difference in the observation period for PIEL > 14 mm (median 15.8 months, 3.4–46.2) and PIEL ≤ 14 mm (median 20.7 months, 3.3–53.1); however, the observation period was significantly shorter in patients with AFP > 20 ng/mL (median

11.9 months, 3.3–53.1) than in patients with AFP ≤ 20 ng/mL (median MCE 22.0 months, 3.4–46.5). To the best of our knowledge, this is the first study to examine the natural history of PIELs on contrast-enhanced sonograms. The study found that the presence of a PIEL > 14 mm was a significant factor for HCC. Interestingly, a previous study reported similar findings regarding hepatic lesion diameter as a risk factor for HCC occurrence;[26] that is, the threshold lesion diameter was 15 mm for hypervascularization and proliferation of early-stage HCC, and in another study, hypo-intense lesions ≥ 15 mm on the liver-specific phase of EOB-MRI were shown to have a propensity for changing to hypervascular lesions.[27] These data are consistent with the significance of the threshold diameter in our study, suggesting strong malignant potential of lesions > 14 mm.