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Liver microRNAs are differentially expressed in human simple steatosis and non alcoholic steatohepatitis with potential repercussions on lipid metabolism and inflammatory status

Non‐alcoholic fatty liver disease is associated with fat deposition in liver. It can present as simple hepatic steatosis (SS) or as non alcoholic steatohepatitis (NASH), which is characterized by inflammation leading to fibrosis. It is unclear which molecular mechanisms differentiate SS and NASH. Progression of SS to NASH is associated with altered hepatic microRNA (miRNA) expression in animal models, but human data are scarce. We analyzed the miRNA expression signature in histology‐proven healthy (H; n= 24), SS (n= 24) or NASH (n= 23) human adult livers by NanoString technology. We found that samples from the 3 groups cluster by disease state based on 142 differentially expressed miRNAs, suggesting that a specific liver miRNA signature distinguishes H, SS and NASH. Putative gene targets of these miRNAs were identified with 12 algorithms and used for gene ontology enrichment analysis. This showed that processes including gene transcription, apoptosis and the TGF‐β signaling pathway are commonly altered between H, SS and NASH. In addition, NASH was associated with altered regulation of lipid storage, IL‐6 and adipocytokine signaling pathways as compared to H and SS and regulation of cholesterol storage as compared to SS. These differences may have therapeutic potential.