Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF).Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses.Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41 +/- 0.85 vs 0.94 +/- 0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF.Conclusions: The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF. (Gut Liver, Published online November 1, 2022)