{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:15:50Z","timestamp":1788498950843,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatitis B virus (HBV) infection remains a global health burden. Although alanine aminotransferase (ALT) is a well-established marker of liver injury, its relationship with immune infiltration, monocyte activation, and inflammatory immune skewing in chronic HBV infection remains incompletely understood. This study aimed to investigate the associations of ALT with liver injury, monocyte infiltration, and hepatic immune microenvironment dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 192 HBV-infected patients and 37 healthy controls were enrolled. Serum ALT, AST, HBV seromarkers, HBV-DNA, alpha-fetoprotein (AFP), and serum fibrosis markers (COLIV, HA, PIIINP, LN) were measured. Univariate and multivariate regression analyses were used to adjust for confounders including age, sex, HBV-DNA, fibrosis markers, and HBeAg status. Transcriptomic data from the GSE84044 liver biopsy cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009105) were analyzed using the xCell algorithm to evaluate hepatic immune infiltration, macrophage polarization, and immune scores. Gene set enrichment analysis (GSEA) was performed to explore monocyte chemotaxis, activation, and WNT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -catenin signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Chronic hepatitis B (CHB) patients showed significantly elevated ALT and AST. Higher ALT levels were strongly associated with elevated fibrosis markers and AFP, indicating more severe liver injury. Peripheral monocytes count and intrahepatic monocyte infiltration were both significantly increased in high-ALT patients. However, after multivariate adjustment, ALT was no longer independently associated with monocyte infiltration, suggesting that the association was largely attributable to overall disease severity rather than a specific ALT-related association. GSEA showed that ALT was positively correlated with monocyte chemotaxis, activation, macrophage differentiation, and WNT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -catenin signaling pathway. Immune landscape analysis revealed a pro-inflammatory immune profile in high-ALT patients, characterized by increased M1 macrophages, CD8+ T cells, and elevated immune scores, accompanied by decreased Tregs and Th1 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Elevated ALT in chronic HBV infection correlates with severe liver injury and a pro-inflammatory, dysregulated hepatic immune microenvironment characterized by enhanced monocyte infiltration and M1 macrophage polarization. Transcriptomic associations reveal a statistical link between WNT\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -catenin signaling activation and hepatic immune dysregulation in HBV-related liver injury; these correlative findings provide preliminary clues for developing immunomodulatory therapeutic strategies for CHB.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1865627","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:26:03Z","timestamp":1788495963000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated ALT correlates with severe liver injury, monocyte infiltration, and Pro-inflammatory immune dysregulation in chronic hepatitis B virus infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Jian","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Clinical 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