Gut Liver.  2023 Sep;17(5):795-805. 10.5009/gnl220022.

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

Affiliations
  • 1The Second Department of Liver Disease Center, Beijing, China
  • 2Departments of Respiration and Infection, Beijing Youan Hospital, Capital Medical University, Beijing, China
  • 3Departments of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
  • 4The First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
  • 5Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China

Abstract

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.

Keyword

Liver failure-associated antigens; Fumarate hydratase; Acute-on-chronic liver failure; Immunoproteomics; Prognosis
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