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Needle-Free Diagnosis of Fatty Liver Disease With New, Non-Invasive Biomarker

A novel biomarker for non-alcoholic fatty liver disease has been discovered using transcriptomic analysis, paving way for non-invasive diagnostic procedures.

With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common type of liver disease, affecting one in four people. Although the early stages of fatty liver are asymptomatic, it can eventually progress to non-alcoholic steatohepatitis (NASH), cirrhosis, liver failure, and even cancer. Fortunately, patients and individuals at risk can still defer this progress by making lifestyle changes in diet and physical exercise as early as possible. Therefore, early diagnosis is key.

Presently, NASH diagnosis involves an invasive liver biopsy, which may cause procedural complications, and further diagnostic confirmation requires a needle biopsy, which is both pricey and variable in terms of sampling and clinical interpretation. However, the recent discovery of a novel biomarker has brought new hope to help simplify diagnostic procedures.

Researchers from Osaka University have identified a new biomarker, known as thrombospondin-2 (TSP-2), that can effectively and non-invasively pinpoint individuals at risk of NAFLD using a simple blood test. Gathering liver tissues from over 300 Japanese and European patients with biopsy-proven NAFLD, the team performed global RNA sequencing on these tissues and identified TSP-2 as a promising biomarker that can help stratify NAFLD patients according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.

Initially, the team observed molecular abnormalities in NASH patients. Further transcriptomic analysis revealed that certain proteins were upregulated during stages 3 and 4 of fibrosis or advanced fibrosis in the NASH stage. One of these proteins were found to be TSP-2, which is encoded by the thrombospondin-2 (THBS2 ) gene.

THBS2 was reported to be positively correlated with inflammation and ballooning, and was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune cell infiltration. In their study, the researchers have established that the expression of THBS2 paralleled clinical indicators traditionally used to categorise the pathological changes observed in NAFLD, including serum enzyme levels, NAFLD Activity Score, and NAFLD Fibrosis Score.

“Remarkably, from the protein patterns, we could not only distinguish NASH from NAFLD, but also determine the molecular hallmarks of NASH pathology. Specifically, we pinpointed that levels of thrombospondin-2 (TSP-2), a glycoprotein encoded by the THBS2 gene, were increased in both NASH and advanced fibrosis,” explained co-first author Kazuhiro Kozumi.

When TSP-2 was measured in 213 patients, they observed that the expression of TSP-2 was significantly higher in NASH than in NAFLD, and correlated with the degree of fibrosis. They also discovered that serum TSP-2 level and platelet count could act as independent predictors of NASH and advanced fibrosis.

These observations suggested that serum TSP-2 levels can be helpful to stratify NAFLD patients and predict the risk of hepatic complications. Additionally, because serum TSP-2 levels can be easily detected in the blood, it bears good prospects of becoming a non-invasive biomarker for NAFLD diagnosis.

“Both hepatic THBS2 gene expression in the liver and serum protein levels of TSP-2 can diagnose cases of NASH and/or advanced fibrosis. A simple and convenient blood test can provide a clinically useful early warning system for complications of NAFLD and inform lifestyle modifications or other interventions that may alter the course of the disease and improve the prognosis,” commented corresponding author Tetsuo Takehara. [APBN]

Source: Kozumi et al. (2021). Transcriptomics Identify Thrombospondin-2 as a Biomarker for Non-alcoholic Steatohepatitis and Advanced Liver Fibrosis. Hepatology.