Abstract
Background
Alcoholic hepatitis (AH) is a widespread and life-threatening chronic liver condition that poses a risk of short-term mortality if not properly managed. Clinicians often encounter challenges due to insufficient knowledge about the underlying mechanisms of AH. This study employs a meta-analysis to identify the molecular mechanisms and potential cell therapy targets for AH.
Methods
We collected four gene expression datasets, three from liver tissues and one from blood tissues, to identify genes associated with AH. Two liver datasets that had data on deaths after steroid treatment in patients with alcoholic hepatitis were also examined to uncover signatures associated with poor prognosis. Additionally, we curated three cohorts, including a mesenchymal stem cell (MSC) intervention group, to identify genes responsive to stem cell interventions. Candidate genes were selected using the inverse weighted variance-based method implemented in the METAL software. We utilized prior knowledge to narrow down potential upstream genes, including a transcription factor (TF) catalog, protein-protein interaction (PPI) networks, disease-gene association databases, and summary statistics for single nucleotide polymorphisms (SNP) linked to disease and expression.
Results
Through four stepwise meta-analyses of nine gene expression datasets, we identified genes targeted by MSC therapy. In detail, the first, second, third, and fourth steps of meta-analysis provided the liver-specific, liver-blood, severe-mortality, and MSC-Tx meta genes linked to AH condition, respectively. Multiple lines of evidence (TF, PPI, and SNP databases) were used to identify 47 AH-related upstream genes.
Conclusions
This study presented critical genes involved in the progression of AH and the therapeutic effects of MSC through meta-analysis. Utilizing these genes, we can confirm genetic changes induced by stem cell treatment, providing a foundation for targeted cell or function-enhanced genetic therapies.