Circulating microRNA Profiles in Patients with Type-1 Autoimmune Hepatitis

Abstract

Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 13 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.

Relation between microRNA‐21, transforming growth factor β and response to treatment among chronic hepatitis C patients

“…This may reflect the fact that the duration of miRNA‐21 upregulation during the course of HCV infection was variable since the time of HCV infection is certainly not known precisely for each patient. Migeta et al have documented a positive correlation between miRNA‐21 and both ALT and AST. They reported that serum miRNA‐21 levels may be related to liver damage activity of HCV.…”

“…However, serum albumin level and platelets count showed a statistically significant increase among HCV patients after receiving treatment. These results were in accordance with Migita et al, who have proposed that the upregulated expression of miRNA‐21 may be due to increased proliferation of liver cells during HCV infection. Additionally, the current study declared an inverse relation between miRNA‐21 and the viral load.…”

Epigenetic changes and their implications in autoimmune hepatitis

“…MiR‐122 modulates hepatic production of cholesterol and lipoproteins . Plasma levels of miR‐122 have also correlated with serum aminotransferase levels in patients with liver disease , and the level of miR‐122 in graft perseveration fluid has been associated with early graft loss after liver transplantation . These findings have supported the consideration of miR‐122 as a biomarker of liver injury .…”

“…Plasma levels of miR‐122 have also correlated with serum aminotransferase levels in patients with liver disease , and the level of miR‐122 in graft perseveration fluid has been associated with early graft loss after liver transplantation . These findings have supported the consideration of miR‐122 as a biomarker of liver injury . Both miR‐21 and miR‐122 have been increased in the circulation of patients with autoimmune hepatitis .…”

“…Autoimmune hepatitis has lagged behind PBC, PSC and NAFLD in exploring epigenetic bases for its variable occurrence and manifestations. Circulating levels of miR‐21 have been differentially elevated in Japanese patients with autoimmune hepatitis, and serum levels of miR‐21 and miR‐122 have reflected serum alanine aminotransferase levels (Table ). Furthermore, the miR‐21 level has correlated directly with the histological grade of inflammation and inversely with the histological stage of fibrosis .…”