Serum Levels of Candida albicans 65-kDa Mannoprotein (CaMp65p) Correlate with Liver Disease in Patients with Alcohol Use Disorder

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, <i>Candida albicans</i> and <i>C. albicans</i>-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific <i>C. albicans</i> antigens that activate Th17 cells during this disease are unknown. The <i>C. albicans</i> 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of <i>C. albicans</i>, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; <i>R</i> = 0.33, <i>p</i> = 0.0092), alanine aminotransferase (ALT; <i>R</i> = 0.27, <i>p</i> = 0.037), gamma-glutamyl transferase (GGT; <i>R</i> = 0.35, <i>p</i> = 0.0055) and alkaline phosphatase (<i>R</i> = 0.36, <i>p</i> = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; <i>R</i> = 0.51, <i>p</i> = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (<i>p</i> = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2-F4 as compared with patients with no or minimal fibrosis F0-F1 (<i>p</i> = 0.0082). The area under the curve (AUC) for detecting F2-F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder.