Extracellular vesicles offer a more precise window into liver injury than traditional blood tests
Researchers from TGen, part of City of Hope, and Johns Hopkins University have found a new set of proteins in the bloodstream that may help identify advanced liver scarring. The 11‑protein signature linked to advanced fibrosis was identified in plasma‑derived extracellular vesicles (EVs), tiny particles that circulate in the bloodstream and carry molecular signals between cells.
Published recently in Cell & Bioscience, the study found that several EV proteins increased in abundance as fibrosis worsened, enabling the signature to distinguish between stage 3 severe fibrosis and stage 4 cirrhosis. The findings point to a promising new avenue for identifying patients at highest risk of liver‑related complications.
A Need for Better Tools to Identify High‑Risk Patients
Metabolic dysfunction–associated steatotic liver disease (MASLD), commonly known as fatty liver disease, affects millions of people and can progress to advanced liver scarring. Advanced fibrosis is strongly associated with liver‑related illness and death, making early identification essential. Yet current blood‑based biomarkers often struggle to detect fibrosis with precision.
To address this challenge, the research team analyzed EVs from 222 adults with MASLD enrolled in a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) research network focused on liver disease. The cohort included individuals with no fibrosis and those with advanced fibrosis, all confirmed by biopsy.
Johanna K. DiStefano, Ph.D., a professor in TGen’s Early Detection and Prevention Division and head of its Metabolic Disease Research Unit, said the study demonstrates that EV cargo provides a clearer snapshot of liver injury than traditional blood tests.
“Identifying which patients will progress to advanced fibrosis before irreversible damage occurs remains a major clinical challenge,” said DiStefano, the senior author of the paper. “By evaluating specific protein signatures within circulating EVs, we can capture the molecular fingerprint of progressive liver injury. This gives us a far clearer picture of disease severity than traditional blood tests, without relying on invasive biopsies.”
She added that the signature’s strength lies not only in its diagnostic performance but also in its biological insight. The EV proteins were tied to immune activation, cellular stress responses and extracellular matrix remodeling, processes central to progressive liver injury.
A Window Into How the Diseased Liver Communicates
EV analysis remains technically complex, meaning a clinical test based on EV biomarkers is not imminent. Still, the findings open new paths for understanding how fibrosis develops and how circulating EVs may influence other organs.
“Rather than looking at all the proteins circulating in blood, we focused on the proteins contained within plasma EVs,” said Patrick Pirrotte, Ph.D., a professor in TGen’s Early Detection and Prevention Division, director of the Integrated Mass Spectrometry Shared Resource at TGen and City of Hope, and first author of the paper. “That allowed us to filter out most of the biological noise and uncover molecular signals associated with advanced fibrosis.”
In ongoing laboratory work, DiStefano’s team is treating healthy liver cells with EVs from individuals with fibrosis to determine how the vesicles affect cellular behavior. They are also studying how activating or suppressing specific EV proteins might alter fibrosis progression.
“Beyond improving detection, these findings provide a functional entry point into potential mechanisms underlying the development of advanced fibrosis,” DiStefano said. ”Understanding these EV protein patterns may bring us closer to both earlier diagnostic tools and targeted therapeutic strategies.
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The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK: R01DK127015, U01DK061732, U01DK061730, U24DK061730); the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Science Award (UM1TR004528); and the National Cancer Institute (P30CA033572) supported this research.
The content of this news release is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NIDDK.
By Becky Ham (TGen)
Posted on Friday, October 09, 2026
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