Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1783
Peer-review started: January 18, 2019
First decision: March 20, 2019
Revised: March 21, 2019
Accepted: March 29, 2019
Article in press: March 30, 2019
Published online: April 21, 2019
Nonalcoholic fatty liver disease (NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack of approved pharmacological interventions for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-fibrosis-the severe histological forms. Over the past decade, tremendous advances have been made in NAFLD research, resulting in the discovery of disease mechanisms and novel therapeutic targets. Hence, a large number of pharmacological agents are currently being tested for safety and efficacy. These drugs are in the initial pharmacological phases (phase 1 and 2), which involve testing tolerability, therapeutic action, and pharmacological issues. It is thus reasonable to assume that the next generation of NASH drugs will not be available for clinical use for foreseeable future. The expected delay can be mitigated by drug repurposing or repositioning, which essentially relies on identifying and developing new uses for existing drugs. Here, we propose a drug candidate selection method based on the integration of molecular pathways of disease pathogenesis into network analysis tools that use OMICs data as well as multiples sources, including text mining from the medical literature.
Core tip: As a proof-of-concept of the advantages that can be yielded by applying multi-omics systems-based approaches to the analysis of potential candidates to the treatment of nonalcoholic steatohepatitis (NASH) we selected the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway map of nonalcoholic fatty liver disease (NAFLD), which illustrates a stage-dependent progression of the disease. After generating a protein−chemical interaction network, we predicted remarkable examples of potential drug repurposing for the treatment of NASH based on the NAFLD-KEGG connectivity map.