Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis

Am J Pathol. 2022 Apr 28:S0002-9440(22)00121-3. doi: 10.1016/j.ajpath.2022.04.004. Online ahead of print.ABSTRACTAlcohol-associated liver disease is a global health care burden, with alcohol-associated cirrhosis (AC) and hepatitis (AH) being two clinical manifestations with poor prognosis. The limited efficacy of standard care for AC and AH highlights a need for therapeutic targets and strategies. The current study aimed to address this need through the identification of hepatic proteome and phosphoproteome signatures of AC and AH. Proteomic and phosphoproteomic analyses were conducted on explant liver tissue (test cohort) and liver biopsies (validation cohort) from AH patients. Changes in protein expression across AH severity and similarities and differences in AH and AC hepatic proteome were analyzed. Significant alterations in multiple proteins involved in various biological processes were observed in both AC and AH, including elevated expression of transcription factors involved in fibrogenesis (eg, Yes1-associated transcriptional regulator). Another finding was elevated levels of hepatic albumin (ALBU) concomitant with diminished ALBU phosphorylation, which may prevent ALBU release, leading to hypoalbuminemia. Furthermore, we observed altered expression of proteins related to neutrophil function and chemotaxis, including elevated myeloperoxidase, cathelicidin antimicrobial peptide, complement C3, and complement C5 in early AH, which declined at later stages. Last, we fou...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research