VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma

Background: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. Methods: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. Results: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, p = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36–38.54), p = 0.020. Conclusions: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response

Development and validation of artificial intelligence to detect and diagnose liver lesions from ultrasound images.

Artificial intelligence (AI) using a convolutional neural network (CNN) has demonstrated promising performance in radiological analysis. We aimed to develop and validate a CNN for the detection and diagnosis of focal liver lesions (FLLs) from ultrasonography (USG) still images. The CNN was developed with a supervised training method using 40,397 retrospectively collected images from 3,487 patients, including 20,432 FLLs (hepatocellular carcinomas (HCCs), cysts, hemangiomas, focal fatty sparing, and focal fatty infiltration). AI performance was evaluated using an internal test set of 6,191 images with 845 FLLs, then externally validated using 18,922 images with 1,195 FLLs from two additional hospitals. The internal evaluation yielded an overall detection rate, diagnostic sensitivity and specificity of 87.0% (95%CI: 84.3-89.6), 83.9% (95%CI: 80.3-87.4), and 97.1% (95%CI: 96.5-97.7), respectively. The CNN also performed consistently well on external validation cohorts, with a detection rate, diagnostic sensitivity and specificity of 75.0% (95%CI: 71.7-78.3), 84.9% (95%CI: 81.6-88.2), and 97.1% (95%CI: 96.5-97.6), respectively. For diagnosis of HCC, the CNN yielded sensitivity, specificity, and negative predictive value (NPV) of 73.6% (95%CI: 64.3-82.8), 97.8% (95%CI: 96.7-98.9), and 96.5% (95%CI: 95.0-97.9) on the internal test set; and 81.5% (95%CI: 74.2-88.8), 94.4% (95%CI: 92.8-96.0), and 97.4% (95%CI: 96.2-98.5) on the external validation set, respectively. CNN detected and diagnosed common FLLs in USG images with excellent specificity and NPV for HCC. Further development of an AI system for real-time detection and characterization of FLLs in USG is warranted