Abstract:Hepatocellular carcinoma (HCC) is a common type of liver cancer whose early-stage diagnosis is a common challenge, mainly due to the manual assessment of hematoxylin and eosin-stained whole slide images, which is a time-consuming process and may lead to variability in decision-making. For accurate detection of HCC, we propose a hybrid deep learning-based architecture that uses transfer learning to extract the features from pre-trained convolutional neural network (CNN) models and a classifier made up of a sequence of fully connected layers. This study uses a publicly available The Cancer Genome Atlas Hepatocellular Carcinoma (TCGA-LIHC)database (n=491) for model development and database of Kasturba Gandhi Medical College (KMC), India for validation. The pre-processing step involves patch extraction, colour normalization, and augmentation that results in 3920 patches for the TCGA dataset. The developed hybrid deep neural network consisting of a CNN-based pre-trained feature extractor and a customized artificial neural network-based classifier is trained using five-fold cross-validation. For this study, eight different state-of-the-art models are trained and tested as feature extractors for the proposed hybrid model. The proposed hybrid model with ResNet50-based feature extractor provided the sensitivity, specificity, F1-score, accuracy, and AUC of 100.00%, 100.00%, 100.00%, 100.00%, and 1.00, respectively on the TCGA database. On the KMC database, EfficientNetb3 resulted in the optimal choice of the feature extractor giving sensitivity, specificity, F1-score, accuracy, and AUC of 96.97, 98.85, 96.71, 96.71, and 0.99, respectively. The proposed hybrid models showed improvement in accuracy of 2% and 4% over the pre-trained models in TCGA-LIHC and KMC databases.