MRI biomarker may predict PSC liver complications: Study
Noninvasive tool may help assess disease severity, study finds
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A noninvasive MRI-based approach may help assess disease severity and predict the likelihood of serious complications in people with primary sclerosing cholangitis (PSC), a study in the U.K. suggested.
The approach measures periductal iron-corrected T1 (Pd-cT1), a marker of inflammation and scarring in liver tissue around the tubes that transport the digestive fluid bile — a hallmark of the disease — without the need for an invasive procedure.
Higher Pd-cT1 levels in PSC patients were linked to markers of more advanced disease. They were also able to predict the likelihood of complications, including worsening liver function, liver transplant, or death.
This study “proposes a non-invasive, objective biomarker” of inflammation and scarring around bile ducts in PSC that, “once validated, may have utility as a monitoring biomarker” in clinical trials, the researchers wrote.
The study, “Periductal iron-corrected T1 is a predictor of adverse outcomes in large-duct primary sclerosing cholangitis,” was published in BMC Medical Imaging.
Measuring ‘onion-skin’ fibrosis
PSC is a chronic form of cholangitis, or inflammation of the bile ducts, the tubes that normally carry bile from the liver to the intestines. Ongoing inflammation can lead to scarring (fibrosis) that narrows or blocks bile ducts inside or outside of the liver, slowing or halting bile flow (cholestasis). This can cause progressive liver damage and eventually liver failure.
“A hallmark [tissue] feature of PSC is concentric periductal fibrosis, also known as “onion-skin” fibrosis,” in which circumferential layers of fibrotic tissue are added around bile ducts, the researchers wrote.
Diagnosis and disease monitoring usually rely on imaging scans and, in some cases, a liver biopsy, in which a small tissue sample is collected for analysis under a microscope. While both approaches can detect bile duct inflammation and fibrosis, they have important limitations.
Biopsy is invasive and may miss affected areas, because PSC tends to damage the liver unevenly. Imaging tests such as magnetic resonance cholangiopancreatography (MRCP), a specialized MRI scan used to visualize the bile ducts, can require the use of a contrast dye, and results may be difficult to interpret consistently.
Because of these challenges, researchers have been exploring MRI techniques that can provide objective measurements of liver tissue changes. One such measure is iron-corrected T1 (cT1), an MRI-derived marker of liver inflammation and fibrosis that can also predict higher risk of liver- and heart-related complications.
The researchers set out to develop a method to measure cT1 specifically in liver tissue surrounding the bile ducts, or Pd-cT1, and to evaluate whether it could predict outcomes in people with large-duct PSC, which affects the large bile ducts.
To do this, the team analyzed data from 72 adults (65% men; median age 44) with large-duct PSC and 20 sex-matched healthy adults (median age 35) who were seen at a hospital in the U.K. PSC patients had been living with the disease for a median of eight years.
All participants underwent two specialized MRI imaging procedures. MRCP was used to create three-dimensional (3D) models of the bile ducts, while the other produced cT1 maps showing levels of inflammation and scarring across the liver. Imaging scans were successfully repeated in 48 PSC patients to evaluate changes over time.
Using imaging software, the researchers aligned the 3D bile duct model with the cT1 maps to measure cT1 in several ring-shaped regions at increasing distance from each bile duct.
Among healthy volunteers, Pd-cT1 values were similar across all measured regions. In contrast, PSC patients showed significantly higher Pd-cT1 values in regions closest to the bile ducts than in farther regions or in the whole liver. The same pattern was seen again one year later in patients with available scans.
In the PSC group, higher Pd-cT1 values in regions closest to the bile ducts were significantly associated with markers of more advanced disease. These included higher liver stiffness, a proxy for liver fibrosis, as well as higher scores on the Enhanced Liver Fibrosis test, a blood test used to assess fibrosis, and the Amsterdam-Oxford Model, a clinical score used to estimate the risk of liver transplant or death in PSC.
Overall, higher Pd-cT1 values in these regions showed a moderate ability to distinguish high-risk patients from those at lower risk based on these markers.
Over a median follow-up of 49 months (just over four years), 24 of the 72 PSC patients experienced at least one adverse outcome, including cholangitis, worsening liver function, liver transplant, or death. Higher Pd-cT1 values in liver tissue near the bile ducts at the study’s start were predictive of a greater risk of these complications.
However, Pd-cT1 values did not predict transplant-free survival, or how long patients live without needing a liver transplant or dying from any cause.
“This study proposes a non-invasive, objective biomarker to assess fibro-inflammation in the [tissues surrounding bile ducts] in PSC,” the researchers wrote. “Once validated … Pd-cT1 could have the potential to serve as a monitoring biomarker and a clinical trial [goal] in high-risk PSC.”
