Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?

Acute liver failure (ALF) is a life-threatening consequence of hepatic function rapid loss without preexisting liver disease. ALF may result in a spectrum of neuropsychiatric symptoms that encompasses cognitive impairment, coma, and often death, collectively defined as acute hepatic encephalopathy. Micro RNAs are small non-coding RNAs that modulate gene expression and are extensively verified as biomarker candidates in various diseases. Our systematic literature review based on the last decade's reports involving a total of 852 ALF patients, determined 205 altered circulating miRNAs, of which 25 miRNAs were altered in the blood, regardless of study design and methodology. Selected 25 miRNAs, emerging predominantly from the analyses of samples obtained from acetaminophen overdosed patients, represent the most promising biomarker candidates for a diagnostic panel for symptomatic ALF. We discussed the role of selected miRNAs in the context of tissue-specific origin and its possible regulatory role for molecular pathways involved in blood-brain barrier function. The defined several common pathways for 15 differently altered miRNAs were relevant to cellular community processes, indicating loss of intercellular, structural, and functional components, which may result in blood-brain barrier impairment and brain dysfunction. However, a causational relationship between circulating miRNAs differential expression, and particular clinical features of ALF, has to be demonstrated in a further study.

Automated summary

Acute liver failure (ALF) is a life-threatening condition characterized by rapid loss of liver function. ALF can cause a range of neuropsychiatric symptoms called acute hepatic encephalopathy. Micro RNAs (miRNAs), small non-coding RNAs that regulate gene expression, have been identified as potential biomarkers for various diseases. In a systematic literature review of 852 ALF patients, 205 altered circulating miRNAs were identified, with 25 miRNAs consistently altered in the blood. These 25 miRNAs, primarily found in patients with acetaminophen overdose, show promise as potential biomarkers for diagnosing symptomatic ALF. The selected miRNAs are believed to play a role in blood-brain barrier function. Further research is needed to establish a causal relationship between differential expression of circulating miRNAs and specific clinical features of ALF.