A research team at Korea University Guro Hospital has discovered a biomarker that can diagnose nonalcoholic steatohepatitis (NASH) using serum microRNA (miRNA).
NASH is a disease that occurs in about 25 percent of patients with nonalcoholic fatty liver disease. Unlike simple fatty liver, the disease can cause inflammation and fibrosis in the liver, which, in turn, can lead to cirrhosis and liver cancer.
Although hospitals can relatively easily diagnose the fatty liver through imaging such as ultrasound, liver biopsy is essential to differentiate between simple fatty liver and NASH accurately. However, it is not easy to perform such liver biopsies due to the high cost of the examination and the possibility of complications, the hospital said. Therefore, there is an urgent need to develop a non-invasive test that can differentiate between simple fatty liver and NASH.
To resolve this issue, the team performed next-generation sequencing (NGS) of miRNAs in the blood of 24 patients diagnosed with NASH through liver biopsy at Korea University Guro Hospital. Afterward, the researchers selected miRNAs with markedly increased expression among 2,588 miRNAs collected from the 24 patients.
As a result, the team confirmed that the expression of four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, miR-4449) significantly increased in NASH patients and was useful for distinguishing between simple fatty liver and NASH.
When the team combined the four miRNAs, the area under the receiver operating characteristic curve (AUC) value indicating the diagnostic accuracy was 0.875, confirming that the team’s method was very effective in distinguishing NASH.
To reconfirm the potential of the four miRNAs as NASH biomarkers, the research team conducted validation using blood samples from 37 NASH patients recruited from Korea University Anam Hospital.
Through the research, it confirmed a similar AUC value of 0.874. Also, the research team integrated and networked the public expression data of the transcriptome so that the results of this study could have a synergistic effect with the results of previous studies on NASH.
Professor Lee Young-sun at the hospital’s Liver Center and Professor Kim Jung-ahn at Korea University College of Medicine led the research.
“Through this study, we confirmed that miRNA in NASH relates to transforming growth factor-β (TGF-β) and Wnt signaling, thereby regulating hepatocyte inflammation and hepatic fibrosis,” Professor Kim said. “Based on the results, we expect it will be possible to discover factors related to the development of diagnostic kits and new drugs.”
Professor Lee also said, “As we have revealed an indicator that can differentiate NASH with blood collection alone, we expect that the study will help prevent the progression to cirrhosis and liver cancer by classifying NASH patients among all nonalcoholic fatty liver disease patients.”
In the future, the team will promote the development of a NASH diagnostic kit using miRNA testing in the blood and a new drug for NASH targeting miRNA, Lee added.
Scientific Reports has published the results of the study.