Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH), and its global prevalence continues to rise. NASH, the progressive form of NAFLD, has higher risks of liver and non-liver related adverse outcomes compared with those patients with NAFL alone. Therefore, the present study aimed to explore the mechanisms in the progression of NAFLD and to develop a model to diagnose NASH based on the transcriptome and epigenome. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) among the three groups (normal, NAFL, and NASH) were identified, and the functional analysis revealed that the development of NAFLD was primarily related to the oxidoreductase-related activity, PPAR signaling pathway, tight junction, and pathogenic Escherichia coli infection. The logistic regression (LR) model, consisting of ApoF, THOP1, and BICC1, outperformed the other five models. With the highest AUC (0.8819, 95%CI: 0.8128–0.9511) and a sensitivity of 97.87%, as well as a specificity of 64.71%, the LR model was determined as the diagnostic model, which can differentiate NASH from NAFL. In conclusion, several potential mechanisms were screened out based on the transcriptome and epigenome, and a diagnostic model was built to help patient stratification for NAFLD populations.

Hepatocellular carcinoma (HCC, LIHC) is a kind of primary liver cancer with high mortality. 1 Genetic and epigenetic changes, chronic hepatitis B, hepatitis C virus infection, aflatoxin exposure, smoking, obesity, and diabetes are the main risk factors for HCC. 2 In recent years, many studies focused on the molecular pathogenesis of HCC and found a series of genetic and epigenetic events that promote the tumorigenesis and development of HCC. 3 Oxidative stress is usually increased in HCC, resulting in the increase of reactive oxygen species (ROS), then resulting in DNA damage, affecting the regulation of cell proliferation-related pathways, thus promoting the tumorigenesis and development of HCC. 4 The repair methods of DNA damage include mismatch repair, excision repair,