Predicting Non-Alcoholic Steatohepatitis: A Lipidomics-Driven Machine Learning Approach

Nonalcoholic fatty liver disease (NAFLD), nowadays the most prevalent chronic liver disease in Western countries, is characterized by a variable phenotype ranging from steatosis to nonalcoholic steatohepatitis (NASH). Intracellular lipid accumulation is considered the hallmark of NAFLD and is associated with lipotoxicity and inflammation, as well as increased oxidative stress levels. In this study, a lipidomic approach was used to investigate the plasma lipidome of 12 NASH patients, 10 Nonalcoholic Fatty Liver (NAFL) patients, and 15 healthy controls, revealing significant alterations in lipid classes, such as glycerolipids and glycerophospholipids, as well as fatty acid compositions in the context of steatosis and steatohepatitis. A machine learning XGBoost algorithm identified a panel of 15 plasma biomarkers, including HOMA-IR, BMI, platelets count, LDL-c, ferritin, AST, FA 12:0, FA 18:3 ω3, FA 20:4 ω6/FA 20:5 ω3, CAR 4:0, LPC 20:4, LPC O-16:1, LPE 18:0, DG 18:1_18:2, and CE 20:4 for predicting steatohepatitis. This research offers insights into the connection between imbalanced lipid metabolism and the formation and progression of NAFL D, while also supporting previous research findings. Future studies on lipid metabolism could lead to new therapeutic approaches and enhanced risk assessment methods, as the shift from isolated steatosis to NASH is currently poorly understood.