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深度学习与数字病理学助力预测脂肪性肝病中肝癌的发展。

Deep learning and digital pathology powers prediction of HCC development in steatotic liver disease.

作者信息

Nakatsuka Takuma, Tateishi Ryosuke, Sato Masaya, Hashizume Natsuka, Kamada Ami, Nakano Hiroki, Kabeya Yoshinori, Yonezawa Sho, Irie Rie, Tsujikawa Hanako, Sumida Yoshio, Yoneda Masashi, Akuta Norio, Kawaguchi Takumi, Takahashi Hirokazu, Eguchi Yuichiro, Seko Yuya, Itoh Yoshito, Murakami Eisuke, Chayama Kazuaki, Taniai Makiko, Tokushige Katsutoshi, Okanoue Takeshi, Sakamoto Michiie, Fujishiro Mitsuhiro, Koike Kazuhiko

机构信息

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.

出版信息

Hepatology. 2025 Mar 1;81(3):976-989. doi: 10.1097/HEP.0000000000000904. Epub 2024 May 20.

Abstract

BACKGROUND AND AIMS

Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease.

APPROACH AND RESULTS

We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets.

CONCLUSIONS

The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.

摘要

背景与目的

识别脂肪性肝病中发生肝细胞癌(HCC)风险较高的患者仍然具有挑战性。我们提出了一种深度学习(DL)模型,使用苏木精和伊红染色的经活检证实的脂肪性肝病全切片图像来预测HCC的发生。

方法与结果

我们纳入了639例活检后≥7年未发生HCC的患者(非HCC组)和46例活检后<7年发生HCC的患者(HCC组)。按活检日期和机构匹配的HCC组和非HCC组配对病例用于训练,其余非配对病例用于验证。DL模型使用从配对病例的全切片图像中裁剪出的28,000个图像块,通过深度卷积神经网络进行训练,预测HCC发生的准确率为81.0%,曲线下面积(AUC)为0.80。使用非配对病例进行验证也显示出良好的准确率,为82.3%,AUC为0.84。这些结果与使用纤维化分期的逻辑回归模型的预测能力相当。值得注意的是,DL模型还检测到了轻度纤维化患者中发生HCC的病例。DL模型生成的显著性图突出了与HCC发生相关的各种病理特征,包括核异型性、高核质比的肝细胞、免疫细胞浸润、纤维化以及缺乏大的脂肪滴。

结论

DL模型捕捉纤维化以外细微病理特征的能力表明其在识别脂肪性肝病患者肝癌发生早期迹象方面的潜力。

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