Alterations in hepatic albumin phosphorylation in patients with alcohol‐associated hepatitis and cirrhosis

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Hardesty, Josiah, Day, Le, Warner, Jeffrey, Zirnheld, Kara, Warner, Dennis, Jacobs, Jon, McClain, Craig, Kirpich, Irina
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R2740

Background Alcohol‐associated liver disease (ALD) encompasses a range of disease states including alcohol‐associated hepatitis (AH) and cirrhosis (AC), two severe clinical manifestations with high mortality due to compromised liver function. One key function of the liver is to synthesize and secrete albumin (ALBU), which plays a critical role in maintaining overall homeostasis. Hypoalbuminemia is a common feature of AH and AC; however, the contributing mechanisms are not established. Recently, S82‐ALBU phosphorylation via FA20A/C was shown to be required for hepatocellular release of ALBU. In this study, we hypothesized that hypoalbuminemia in AH and AC may occur in part due to hepatocellular retention secondary to compromised ALBU phosphorylation. Methods Proteomic and phosphoproteomic analyses were conducted using LC/MS/MS on liver biopsy samples from AH patients (n=34), AC patients (n=10), and non‐ALD controls (n=10). Further, AH patients were stratified by MELD score (Model for End‐stage Liver Disease) as follows: AH1 (MELD 17‐20), AH2 (21‐25), AH3 (26‐29), and AH4 (30‐37). Significantly changed proteins were correlated with MELD and compared between non‐surviving and surviving AH patients. One‐way ANOVA was used for comparisons between three groups (parametric), unpaired Student’s t‐test was used for two groups (parametric), and Pearson’s correlation was used for regression analysis. A p