Identification of circulating microRNAs as potential biomarkers for hepatic necroinflammation in patients with autoimmune hepatitis

Chisato Saeki, Juntaro Matsuzaki, Masahiko Kuroda, Koji Fujita, Makiko Ichikawa, Satoko Takizawa, Keiko Takano, Tsunekazu Oikawa, Yasuni Nakanuma, Masayuki Saruta, Takahiro Ochiya, Akihito Tsubota

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective MicroRNAs (miRNAs) are implicated in the pathogenesis of autoimmune diseases and could be biomarkers of disease activity. This study aimed to identify highly expressed circulating miRNAs in patients with autoimmune hepatitis (AIH) and to evaluate their association with clinical characteristics. Methods Microarray analyses were performed, and miRNA expression profiling for AIH, primary biliary cholangitis (PBC) and overlap syndrome (OS) using the serum of patients and healthy individuals was done. Samples were divided into discovery and test sets to identify candidate miRNAs that could discriminate AIH from PBC; the former included 21 AIH and 23 PBC samples, while the latter included five AIH and eight PBC samples. Results Among 11 candidate miRNAs extracted in the discovery set, 4 (miR-3196, miR-6125, miR-4725-3 p and miR-4634) were specifically and highly expressed in patients with AIH in the test set. These four miRNAs discriminated AIH from PBC with high sensitivity (0.80-1.00) and specificity (0.88-1.00). In situ hybridisation analysis revealed that these miRNAs were expressed in the cytoplasm of hepatocytes in patients with AIH. Their expression levels were highest in untreated patients with AIH, followed by those in untreated patients with OS. They drastically or moderately decreased after prednisolone treatment. Histological analysis demonstrated that the expression levels of miR-3196, miR-6125 and miR-4634 in patients with AIH and OS were correlated with severe hepatic necroinflammatory activity. Conclusion These circulating miRNAs are suggested to reflect hepatic necroinflammatory activity and serve as AIH-related and treatment-responsive biomarkers. These miRNAs could be beneficial in developing new therapeutic strategies for AIH.

Original languageEnglish
Article numbere000879
JournalBMJ Open Gastroenterology
Volume9
Issue number1
DOIs
Publication statusPublished - 2022 Apr 4

Keywords

  • AUTOIMMUNE LIVER DISEASE
  • PRIMARY BILIARY CIRRHOSIS
  • autoimmune hepatitis
  • biomarker
  • circulating microRNA

ASJC Scopus subject areas

  • Gastroenterology

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