Circulating complement factor H levels are associated with disease severity and relapse in autoimmune hepatitis.

Abstract

Background & Aims:

The complement system plays pivotal roles in innate immunity. Mannose-binding lectin-associated serine protease (MASP)-2 plays essential roles in the activation of the lectin complement pathway. Complement factor H acts as a critical negative regulator of the alternative complement pathway. The association of circulating MASP-2 and factor H with the clinical features of patients with autoimmune hepatitis (AIH) is unclear.

Methods:

A total of 63 patients with AIH were recruited for this study. The serum levels of MASP-2, factor H, and C3a were measured, and their associations with the clinical features of AIH were analyzed.

Results:

The circulating C3a levels were higher in patients with AIH than in the controls. The circulating MASP-2 and factor H levels were decreased depending on the severity of AIH. Multivariate logistic analysis showed that low circulating factor H levels were associated with features of severe AIH (odds ratio 0.36; 95% CI 0.15-0.84; p = 0.018). Multivariate Cox proportional hazards model analysis showed that low circulating factor H levels were associated with a high incidence of relapse (hazard ratio: 5.19; 95% CI 1.07-25.2; p = 0.041). Patients with low circulating factor H levels showed higher rates of relapse than the controls (log-rank, p = 0.006).

Conclusion:

Circulating factor H levels were associated with severe disease and with the incidence of relapse, suggesting a role for the complement system in the pathophysiology of AIH.

Lay summary:

Autoimmune hepatitis is an immune-mediated liver disease. Despite effective treatments, patients often relapse, which can lead to clinical deterioration and adverse outcomes. Herein, we studied the importance of the complement system (a form of innate immunity) in patients with autoimmune hepatitis. We found that the levels of a protein called factor H, which regulates the complement system, could be a potential biomarker of disease severity and relapse, and could even have therapeutic potential for patients with AIH.

• Authors: Manabu Hayashi, Kazumichi Abe, Masashi Fujita, Atsushi Takahashi, Hideharu Sekine, Hiromasa Ohira
• Journal: JHEP reports : innovation in hepatology (JHEP Rep) Vol. 4 Issue 7 Pg. 100497 (Jul 2022) ISSN: 2589-5559 [Electronic] Netherlands
• PMID: 35677590 (Publication Type: Journal Article)
• Copyright: © 2022 The Author(s).