The gold standard for diagnosing liver disease is a liver biopsy, but researchers are seeking a simpler way to identify those at risk, given the silent nature of early disease and rising incidence around the globe.
In a recent study, researchers said they found a biomarker that can be used to diagnosis nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide and a risk factor for cirrhosis, liver failure or cancer.
Currently, diagnosing NAFLD or nonalcoholic steatohepatitis (NASH) requires an invasive needle biopsy, which carries risks of complications, sampling errors, and cost. With the incidence of NAFLD increasing, affecting one-fourth of the world’s population due to rising obesity, and because the beginning stages of liver damage are asymptomatic, there is a need for earlier, easier identification methods, said the authors, writing in Hepatology.
Researchers from Japan and the United Kingdom conducted a retrospective multicenter cohort study, enrolling a total of 311 biopsy-proven NAFLD patients diagnosed in 3 Japanese hospitals between 2014 and 2020.
Inclusion criteria included the presence of fatty liver by liver imaging test, persistent increases in liver enzyme levels, the absence of chronic liver disease other than NAFLD, and alcohol consumption less than 20 grams per day.
Using whole-genome transcriptomics, they analyzed liver tissues from 98 patients with biopsy-proven NAFLD (51 with NAFL and 47 with NASH).
The analysis identified proteins predicted to be secreted from the liver, including matricellular glycoprotein thrombospondin-2 (TSP-2), encoded by the thrombospondin 2 (THBS2) gene.
THBS2 expression in liver cells paralleled the inflammation and ballooning that signal disease, including serum enzyme levels, NAFLD Activity Score and NAFLD Fibrosis Score. THBS2 was linked with "extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune cell infiltration," the report said.
Serum TSP-2 level and platelet count were independent predictors of NASH and advanced fibrosis, and serum TSP-2 levels could stratify patients according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events, such as esophageal varix, ascites, and hepatic encephalopathy.
"Serum levels of TSP-2 in NAFLD patients were significantly higher in NASH than in NAFL," author Takahiro Kodama, MD, Department of Gastroenterology and Hepatology, Osaka Graduate School of Medicine, Suita, Japan, said in a statement. Notably, "the increase tallied with the degree of fibrosis," he added.
In addition, the authors identified 136 significantly upregulated genes possibly involved in molecular pathogenesis of NASH; they found overlap with 95 genes upregulated in the transcriptome dataset of patients with NAFLD in a European registry; the "overlap strengthens the validity of our transcriptome analysis," the authors said.
Kozumi K, Kodama T, Murai H, et al. Transcriptomics identify thrombospondin-2 as a biomarker for nonalcoholic steatohepatitis and advanced liver fibrosis. Hepatology. Published online June 9, 2021 doi: 10.1002/hep.31995