Circulating miR-148a is a precipitant independent biomarker of acute-on-chronic liver failure (ACLF)

Background/aim Bacterial infection (BI) is a common trigger of ACLF. We aimed to identify differentially expressed genes (DEGs) and miRNAs in a BI-ACLI model mimicking ACLF.

Methods Either saline or LPS (4 mg/kg) was intraperitoneally injected to C57BL/6J (n=16) and Abcb4-/- (n=16) mice. Constructed mRNA libraries (NebNext Ultra-II RNA kit) were used to reveal DEGs (NextSeq500, Illumina). Samples were screened for miRNAs (miScript, Qiagen). Identified miRNAs were evaluated in serum of chronic liver disease (CLD) patients with (n=10) or without BI (n=37), ACLF patients (n=9 grade I and n=26 grade II; n=7 BI-ACLF, n=28 nonBI-ACLF) and healthy controls (HC) (n=7) by TaqMan assays.

Results A total of 145 DEGs (127 overexpressed; 18 repressed) were identified in LPS-treated KO mice. qRT-PCR confirmed upregulation of Rantes, Il-22, Il-2 and Il-6. Significant upregulations and repressions of M1 and M2 macrophages respectively were observed. Among 7 identified miRNAs, overexpression was present only in mir148a-3p in CLD with concurrent BI (time of BI detection < 2 weeks, n=15), compared to those without BI (p < 0.05, n=37), and HCs (p < 0.01). miR-148a upregulation was also evident in ACLF patients, regardless of whether acute trigger was BI or not. Elevation was more prominent in grade II patients compared to grade I (26.9 vs 7.44-fold, p < 0.05). None of the identified DEGs was among up-to-date targets of miR-148a, suggesting the presence of a previously unidentified target.

Conclusions Circulating miR-148a can be a trigger-independent biomarker for ACLF, the target of which is yet to be identified.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022