Galectin-9 in autoimmune hepatitis Correlation between serum levels of galectin-9 and M2BPGi in patients with autoimmune hepatitis

Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients. We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups. Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 +/- 4.9ng/mL vs 8.9 +/- 3.0ng/mL, P<.001) or healthy controls (13.8 +/- 4.9ng/mL vs 5.0 +/- 1.3ng/mL, P<.001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 +/- 4.9ng/mL vs 8.3 +/- 3.8 ng/mL, P<.001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels. Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.