PNNL

Abstract

Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease (ALD). AH has a poor prognosis and the first line of therapy is corticosteroids, to which some patients do not respond. The mechanisms underlying non-response to corticosteriods are not fullly undersood. This study aimed to identify hepatic proteomic markers that may influence a positive response to corticosteroid therapy and prognosis. Thus, significantly reduced levels of the glucocorticoid receptor and its transcriptional co-activator, GMEB2, were found in the hepatic proteome of AH non-responders vs responders. The corticosteroid metabolizing enzyme, DHI1, was increased in AH non-responders vs. responders. Other pathways altered included heat shock and mitochondrial DNA repair. An analysis of differentially expressed proteins in non-responders who survived to 24 weeks relative to those who did not also identified several pathways that may play a role in mortality in these individuals. These findings shed light into the mechanisms of non-response of AH patients to corticosteroid therapy and help to explain the worsened outcomes as a result.