Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

Abstract

Autoimmune hepatitis (AIH) is an autoimmune liver disease that is characterized by a progressive destruction of the liver parenchyma and the development of liver fibrosis. We aimed to examine the relationship between circulating cytokines/chemokines and the Mac-2 binding protein glycosylation isomer (M2BPGi) levels in Japanese patients with autoimmune hepatitis (AIH).We investigated the relationship between circulating cytokines/chemokines and M2BPGi levels in Japanese patients with AIH. Seventy-seven patients with well-documented AIH were enrolled in the National Hospital Organization (NHO)-AIH-liver-network database. We measured the serum levels of 20 cytokines in 31 selected AIH patients before and after steroid treatment using multisuspension cytokine array.Eleven cytokines and soluble adhesion molecules were increased in untreated AIH patients compared with treated AIH patients. Among these cytokines and soluble adhesion molecules, soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-γ-inducible protein 10 (IP-10) were most downregulated by steroid therapy in AIH patients. We measured serum sICAM-1 and IP-10 by ELISA and found the levels were significantly higher in AIH patients (n = 77) compared with chronic viral hepatitis C patients (n = 32). Furthermore, there was a positive correlation between sICAM-1 or IP-10 and alanine aminotransferase, total bilirubin, and circulating M2BPGi levels. M2BPGi levels were increased in AIH patients with high stages of liver fibrosis. Additionally, M2BPGi levels were correlated with the histological grade of inflammation in AIH. Circulating M2BPGi levels were significantly reduced by steroid treatment in AIH patients.sICAM-1 and IP-10 are useful markers to assess immune-mediated hepatitis activity in AIH and they correlate with circulating M2BPGi. Serum M2BPGi levels increased in untreated AIH patients with active hepatitis and were decreased by steroid therapy. M2BPGi reflects autoimmune-mediated hepatic inflammation as well as liver fibrosis.

Recent updates on the management of autoimmune hepatitis

“…A novel serum fibrosis marker, i.e., Mac-2 binding protein glycosylation isomer (M2BPGi), which was originally reported to be associated with the fibrosis stage in CHC patients [ 24 ], is likely to become an alternative to the use of VCTE; the M2BPGi value is influenced by both inflammation and fibrosis in AIH patients, in a similar way to VCTE [ 25 ]. A ‘one-serum parameter fits all’ approach to the evaluations of disease activity and fibrosis could be achievable with serum M2BPGi, but further studies are necessary to validate its utility.…”

Autoimmune Hepatitis: 2019 Update

“…Although close monitoring of fibrosis staging is essential during the clinical course, it is not feasible to carry out serial liver biopsies, and the role of noninvasive indices for fibrosis staging has been paid more attention to recently. These indices include biochemical calculation scores, such as the aspartate aminotransferase/platelet ratio (APRI) or fibrosis index based on the 4 factors (FIB-4), 24 Mac-2 binding protein glycosylation isomer, 25 magnetic resonance elastography, 26 and transient elastography. 27,28 A recent systematic review indicated that transient elastography had a good performance for determining significant fibrosis, advanced fibrosis, and cirrhosis, whereas APRI and FIB-4 showed poor performance.…”

Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

“… 36 37 In addition, RAAS inhibitors are protective effectors for diabetic retinopathy. 38 Furthermore, intercellular adhesion molecule-1 is associated with liver fibrosis, 39 and diabetic microangiopathy 40 and macroangiopathy. 41 Thus, M2BPGi, which is a surrogate marker of liver fibrosis, has a close association with diabetic microangiopathy and macroangiopathy.…”