{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:14:11Z","timestamp":1788506051174,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":245,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Entecavir (ETV) combined with pegylated interferon alpha (PEG\u2010IFN\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ) improves chronic hepatitis B (CHB) functional cure rates, but therapeutic heterogeneity and underlying metabolic mechanisms remain unclear. This study used untargeted metabolomics to identify metabolic signatures, mechanisms, and predictive biomarkers of functional cure with ETV\u2010PEG\u2010IFN\n                      <jats:italic>\u03b1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010eight CHB patients were grouped into ETV monotherapy (Group E,\n                      <jats:italic>n<\/jats:italic>\n                      = 12) and ETV\u2010PEG\u2010IFN\n                      <jats:italic>\u03b1<\/jats:italic>\n                      combination therapy (Group Z,\n                      <jats:italic>n<\/jats:italic>\n                      = 26); Group Z was subdivided into cured (Group A,\n                      <jats:italic>n<\/jats:italic>\n                      = 13) and noncured (Group B,\n                      <jats:italic>n<\/jats:italic>\n                      = 13). Serum metabolomic profiling, multivariate statistics, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified differential metabolites. A random forest model was built using key metabolites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three hundred eighty\u2010eight metabolites were identified. Four differential metabolites distinguished Group A and B (upregulated guanidinoacetic acid, uracil 5\u2010carboxylate; downregulated L\u2010methionine S\u2010oxide, oleamide), enriching amino acid metabolism pathways. Nine differential metabolites between Group E and Z implicated amino acid, immune, and fatty acid pathways. The random forest model based on the four Group A\/B metabolites showed 88.5% cross\u2010validation accuracy (AUC = 0.920), with L\u2010methionine S\u2010oxide and oleamide as key predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study reveals metabolic rewiring in CHB functional cure via ETV\u2010PEG\u2010IFN\n                      <jats:italic>\u03b1<\/jats:italic>\n                      therapy, involving energy metabolism, oxidative stress, and immunomodulation, based on which we propose a tentative metabolism\u2010immunity synergy model to guide future research. Key metabolites, especially L\u2010methionine S\u2010oxide and oleamide, show exploratory predictive potential for functional cure that warrants further validation in independent cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/bmri\/1031453","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:52:46Z","timestamp":1788504766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomics Reveals Metabolic Characteristics of Functional Cure in Chronic Hepatitis B Treated With Entecavir Combined With Pegylated Interferon 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