AUTHOR=Zhao Mingjiu , Lei Yu , Zhou Yanyan , Sun Mingan , Li Xia , Zhou Zhiguang , Huang Jiaqi , Li Xinyu , Zhao Bin TITLE=Development and investigation of metabolism-associated risk assessment models for patients with viral hepatitis JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 13 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1165647 DOI=10.3389/fcimb.2023.1165647 ISSN=2235-2988 ABSTRACT=Dysregulation of metabolism plays an important role in the onset and progression of multiple pathogenic diseases, including viral hepatitis. However, a model to predict viral hepatitis risk by metabolic pathways is still lacking. Thus, we developed two risk assessment models for viral hepatitis based on metabolic pathways identified through univariate and LASSO Cox regression analysis. The first model is designed to assess the progression of the disease, by evaluating changes in the Child-Pugh class, hepatic decompensation, and development of hepatocellular carcinoma. The second model is focused on determining the prognosis of the illness, taking into account the patient's cancer status. Our models were further validated by Kaplan–Meier plots of survival curves. In addition, we investigated the contribution of immune cells in metabolic processes and identified two distinct subsets of macrophages and NK cells that have significant impacts on metabolic pathways. Specifically, our findings suggest that resting or inactive macrophages and NK cells contributed to maintaining metabolic homeostasis, particularly with regard to lipid and α-amino acid metabolism, thereby potentially reducing the risk of viral hepatitis progression. In conclusion, our study offers a useful tool for early disease detection in viral hepatitis patients through metabolic pathway analysis and sheds light on the immunological understanding of the disease through the examination of immune cell metabolic disorders.