Hepatic Macrophage activation and the LPS pathway in patients with different degrees of severity and histopathological patterns of drug induced liver injury

xlomafota13 shared this article with you from Inoreader Hepatic Macrophage activation and the LPS pathway in patients with different degrees of severity and histopathological patterns of drug induced liver injury Via Cellular and Molecular Biology Histol Histopathol. 2021 Apr 15:18340. doi: 10.14670/HH-18-340. Online ahead of print. ABSTRACT BACKGROUND: Inflammatory activation of hepatic macrophages plays a primary role in drug-induced liver injury (DILI). However, the exact mechanism underlying DILI remains unclear. METHODS: A total of 328 DILI patients and 80 healthy individuals were prospectively enrolled in this study. The DILI patients were categorized into subgroups based on either disease severity or histopathological patterns. Plasma soluble CD163 (sCD163) and hepatic CD163 were examined to determine hepatic macrophage activation, and CD8, CD20, and MUM-1 were assessed to determine cellular immunity using immunohistochemistry. The lipopolysaccharide (LPS) pathway proteins [e.g. LPS, soluble CD14 (sCD14), and LPS-binding protein (LBP)] were measured using enzyme-linked immunosorbent assay. RESULTS: Plasma sCD163 levels were nine-fold higher in DILI patients th an in healthy controls at the baseline, but significantly decreased at the 4-week follow-up visit after treatment. The numbers of hepatic macrophages, B cells, and plasma cells were significantly higher in the liver tissues from DILI patients than those from healthy controls. Furthermore, the baseline levels of LPS pathway proteins in the DILI patients were significantly higher than those in the controls. Notably, these proteins significantly decreased at the 4-week follow-up visit but remained significantly higher than the levels for the controls. CONCLUSIONS: Hepatic inflammation in DILI involves the activation of hepatic macrophages and cellular immunity, in which the LPS pathway likely plays a role, at least in part. As such, this study has improved our understanding of the pathological mechanisms for DILI and may facilitate the development of better treatments for patients with DILI. PMID:33870482 | DOI:10.14670/HH-18-340 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.