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Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound

January 1, 2020 — American Journal of Roentgenology (AJR)


OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules.

MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3–4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves.

RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%).

CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

Authors: Manxia Lin1, David S. Lu2, Yu Duan1, Penan Liao3,4, James Sayre2, Xiaoyan Xie1 and Ming Kuang1,5

1Department of Medical Ultrasonics, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhong Shan Rd 2, Yuexiu, Guangzhou 510080, People’s Republic of China; 2Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA; 3Department of Radiology, Cathay General Hospital, Taipei, Taiwan; 4School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 5Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China.

American Journal of Roentgenology: 1-9. 10.2214/AJR.19.21739

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