Non-alcoholic fatty liver disease (NAFLD) is one of the most widespread liver disorders on a global scale, posing a significant threat of progressing to more severe conditions like nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma. Diagnosing and staging NAFLD presents challenges due to its non-specific symptoms and the invasive nature of liver biopsies. Our research introduces a novel artificial intelligence cascade model employing ensemble learning and feature fusion techniques. We developed a non-invasive, robust, and reliable diagnostic artificial intelligence tool that utilizes anthropometric and laboratory parameters, facilitating early detection and intervention in NAFLD progression. Our novel artificial intelligence achieved an 86% accuracy rate for the NASH steatosis staging task (non-NASH, steatosis grade 1, steatosis grade 2, and steatosis grade 3) and an impressive 96% AUC-ROC for distinguishing between NASH (steatosis grade 1, grade 2, and grade3) and non-NASH cases, outperforming current state-of-the-art models. This notable improvement in diagnostic performance underscores the potential application of artificial intelligence in the early diagnosis and treatment of NAFLD, leading to better patient outcomes and a reduced healthcare burden associated with advanced liver disease.

We present a system for anomaly detection in histopathological images. In histology, normal samples are usually abundant, whereas anomalous (pathological) cases are scarce or not available. Under such settings, one-class classifiers trained on healthy data can detect out-of-distribution anomalous samples. Such approaches combined with pre-trained Convolutional Neural Network (CNN) representations of images were previously employed for anomaly detection (AD). However, pre-trained off-the-shelf CNN representations may not be sensitive to abnormal conditions in tissues, while natural variations of healthy tissue may result in distant representations. To adapt representations to relevant details in healthy tissue we propose training a CNN on an auxiliary task that discriminates healthy tissue of different species, organs, and staining reagents. Almost no additional labeling workload is required, since healthy samples come automatically with aforementioned labels. During training we enforce compact image representations with a center-loss term, which further improves representations for AD. The proposed system outperforms established AD methods on a published dataset of liver anomalies. Moreover, it provided comparable results to conventional methods specifically tailored for quantification of liver anomalies. We show that our approach can be used for toxicity assessment of candidate drugs at early development stages and thereby may reduce expensive late-stage drug attrition.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder characterized by the excessive accumulation of fat in the liver in individuals who do not consume significant amounts of alcohol, including risk factors like obesity, insulin resistance, type 2 diabetes, etc. We aim to identify subgroups of NAFLD patients based on demographic, clinical, and genetic characteristics for precision medicine. The genomic and phenotypic data (3,408 cases and 4,739 controls) for this study were gathered from participants in Mayo Clinic Tapestry Study (IRB#19-000001) and their electric health records, including their demographic, clinical, and comorbidity data, and the genotype information through whole exome sequencing performed at Helix using the Exome+$^\circledR$ Assay according to standard procedure (www$.$helix$.$com). Factors highly relevant to NAFLD were determined by the chi-square test and stepwise backward-forward regression model. Latent class analysis (LCA) was performed on NAFLD cases using significant indicator variables to identify subgroups. The optimal clustering revealed 5 latent subgroups from 2,013 NAFLD patients (mean age 60.6 years and 62.1% women), while a polygenic risk score based on 6 single-nucleotide polymorphism (SNP) variants and disease outcomes were used to analyze the subgroups. The groups are characterized by metabolic syndrome, obesity, different comorbidities, psychoneurological factors, and genetic factors. Odds ratios were utilized to compare the risk of complex diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), as well as liver failure between the clusters. Cluster 2 has a significantly higher complex disease outcome compared to other clusters. Keywords: Fatty liver disease; Polygenic risk score; Precision medicine; Deep phenotyping; NAFLD comorbidities; Latent class analysis.

Non alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, which can be predicted accurately to prevent advanced fibrosis and cirrhosis. While, a liver biopsy, the gold standard for NAFLD diagnosis, is invasive, expensive, and prone to sampling errors. Therefore, non-invasive studies are extremely promising, yet they are still in their infancy due to the lack of comprehensive research data and intelligent methods for multi-modal data. This paper proposes a NAFLD diagnosis system (DeepFLDDiag) combining a comprehensive clinical dataset (FLDData) and a multi-modal learning based NAFLD prediction method (DeepFLD). The dataset includes over 6000 participants physical examinations, laboratory and imaging studies, extensive questionnaires, and facial images of partial participants, which is comprehensive and valuable for clinical studies. From the dataset, we quantitatively analyze and select clinical metadata that most contribute to NAFLD prediction. Furthermore, the proposed DeepFLD, a deep neural network model designed to predict NAFLD using multi-modal input, including metadata and facial images, outperforms the approach that only uses metadata. Satisfactory performance is also verified on other unseen datasets. Inspiringly, DeepFLD can achieve competitive results using only facial images as input rather than metadata, paving the way for a more robust and simpler non-invasive NAFLD diagnosis.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) establishes new criteria for diagnosing fatty liver disease independent of alcohol consumption and concurrent viral hepatitis infection. However, the long-term outcome of MAFLD subjects is sparse. Few articles are focused on mortality in MAFLD subjects, and none investigate how to predict a fatal outcome. In this paper, we propose an artificial intelligence-based framework named MAFUS that physicians can use for predicting mortality in MAFLD subjects. The framework uses data from various anthropometric and biochemical sources based on Machine Learning (ML) algorithms. The framework has been tested on a state-of-the-art dataset on which five ML algorithms are trained. Support Vector Machines resulted in being the best model. Furthermore, an Explainable Artificial Intelligence (XAI) analysis has been performed to understand the SVM diagnostic reasoning and the contribution of each feature to the prediction. The MAFUS framework is easy to apply, and the required parameters are readily available in the dataset.