Immune Reactivity Is More Suppressed in Patients with Alcoholic Liver Disease than in Patients with Virus‐Induced Cirrhosis after CRH Stimulation

Abstract
The most frequent diagnoses for liver transplantation are virus-induced cirrhosis (VIC) and alcoholic liver disease (ALD), after an abstinence period of at least 6 months. Chronic ethanol consumption has been linked to an abnormal neuroendocrine-immune axis and to an altered surgical stress response inducing an increased infection rate. Preoperative stress testing might be relevant to detect stress-induced immune alteration. The aim of this study was to investigate the preoperative stress-like response to corticotrophin-releasing-hormone challenge (CRH) of patients with ALD compared with patients with VIC and their immune sequelae. Nine patients with ALD and 8 patients with VIC were included in this clinical study prior to transplantation. All patients received CRH in the morning. Blood samples were drawn before and after stress testing. In response to CRH, the ALD patients showed a significant decrease in the plasma interleukin (IL)-6/IL-10 ratio. After lipopolysaccharide stimulation of whole blood from CRH-challenged ALD patients, IL-10 increased significantly. The cytotoxic T1-(Tc1) to cytotoxic T2 (Tc2) ratio was significantly decreased in ALD patients after the stress test. Infections occurred significantly more often in ALD patients within the past year before study inclusion. ALD patients showed a stronger anti-inflammatory immune status and response than VIC patients. This difference was associated with a higher infection rate despite a median alcohol abstinence time of 3.5 years. Although an altered immune response is well known among patients with actual alcohol-use disorders, to the best of our knowledge, it is not described in patients after such a long abstinence time.