Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury

• Published in: Journal of clinical and translational hepatology Vol. 6; no. 4; pp. 345 - 349
• Main Authors: Shabat, Yehudit, Ya'acov, Ami Ben, Ilan, Yaron
• Format: Journal Article
• Language: English
• Published: China Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel 28.12.2018; XIA & HE Publishing Inc
• Subjects: Original; Alpha-1 anti-trypsin; Drug-induced liver injury; Chronic liver disease; Acetaminophen; Druginduced liver injury
• ISSN: 2225-0719; 2310-8819
• DOI: 10.14218/JCTH.2018.00030

The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage. AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage. Mice were followed for changes in serum levels of liver enzymes, liver histology, and for interferon gamma serum levels. Treatment with AAT alleviated concanavalin A-induced immune-mediated liver damage, as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma, and an improved lymphocyte infiltration into the liver on liver biopsies. Moreover, treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury. AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage. The data support its potential use in patients with immune-associated liver disorders.