Alpha-1 antitrypsin (AAT) has been shown to have potential anti-inflammatory activity in several preclinical and clinical trials. The present study evaluated the role of AAT in ALD.

In all, 512 patients with cirrhosis were clinically characterized. Investigators compared the survival, clinical and biochemical parameters including serum concentration of AAT between patients with ALD and liver disease due to other causes. The role of AAT was also assessed in experimental ALD models.

Cirrhotic ALD patients with AAT serum concentrations <120 mg/dL were shown to have a significantly increased risk for death/liver transplantation over patients with AAT serum concentrations >120 mg/dL. According to the multivariate Cox regression analysis, low AAT serum concentration served as a NaMELD-independent predictor of survival/transplantation.

Ethanol-fed experimental models had a significant reduction in hepatic AAT in comparison with pair-fed models. hAAT-Tg models were ethanol-fed, and demonstrated protection from liver injury associated with decreased steatosis, hepatic neutrophil infiltration and decreased expression of proinflammatory cytokines.

In order to investigate the therapeutic capability of AAT, ethanol-fed models were treated with human AAT which alleviated hepatic injury, neutrophil infiltration and steatosis.

The study thus revealed that cirrhotic ALD patients with AAT concentrations below 120 mg/dL had an increased risk for death/liver transplantation. Both hAAT-Tg models and AAT-treated models exhibited protection from ethanol-induced liver injury. AAT could thus be a treatment option for human ALD, particularly alcoholic hepatitis.

Source: Grander C, Schaefer B, Schwärzler J, et al.Alpha-1 antitrypsin governs alcohol-related liver disease in mice and humans.Gut. 2020 Jul 22;gutjnl-2020-321375.