High proton density fat fraction (PDFF) on liver magnetic resonance imaging (MRI) is linked to significantly elevated risks for liver cancer, non-alcoholic steatohepatitis (NASH), cirrhosis, and other forms of liver disease, according to a new study involving over 378,000 participants.
For the prospective study, recently reported in Radiology, researchers reviewed MRI data from 378,436 people in the UK Biobank database and utilized a polygenic risk score weighted by liver MRI PDFF findings to ascertain related risks for various liver diseases.
The researchers found that people with a high MRI PDFF had a 7.7-fold higher risk for NASH, triple the risk for fibrosis and cirrhosis of the liver, and a 4.4-fold elevated risk for non-alcoholic fatty liver disease (NAFLD).
“We found evidence of a significant positive genetic correlation between liver MRI PDFF and several liver disease risks … . Further mediation analysis suggested that liver MRI PDFF may serve as a possible ‘transfer station’ between the etiologic factors (high-density lipoprotein cholesterol, type 2 diabetes mellitus, and waist-to-hip ratio) and (the aforementioned) liver diseases. These findings are important for better prevention (for) liver health by MRI PDFF dynamic monitoring,” wrote lead study author Tianyi Xia, M.D., who is associated with the Jiangsu Key Laboratory of Molecular and Functional Imaging within the Department of Radiology at Zhongda Hospital and the School of Medicine at Southeast University in Nanjing, China, and colleagues.
In a large prospective study involving MRI data from 378,436 people, researchers found that people with a high MRI PDFF had a 7.7-fold higher risk for NASH, triple the risk for fibrosis and cirrhosis of the liver, a 4.4-fold elevated risk for non-alcoholic fatty liver disease (NAFLD), and elevated risks for other liver diseases.
A high MRI PDFF was also associated with a 1.9-fold higher risk for alcoholic liver disease and a 4.5-fold higher risk for malignant liver neoplasm, according to the study authors.
“Hepatocellular carcinoma, which is one of the most common liver malignancies and a leading cause of cancer-related mortality worldwide, has a predominance of NAFLD, NASH, and alcohol in European populations,” added Xia and colleagues. “Abnormal lipid metabolism promoting hepatocellular carcinoma is influenced by impaired immunologic function, pathologic inflammatory responses, and metabolic and oxidative stress specific to the liver.”
Three Key Takeaways
- High MRI PDFF is a significant risk factor. Individuals with a high MRI PDFF in their liver are at significantly elevated risk for various liver diseases, including non-alcoholic steatohepatitis (NASH), cirrhosis, and non-alcoholic fatty liver disease (NAFLD). The study found a 7.7-fold higher risk for NASH, triple the risk for fibrosis and cirrhosis, and a 4.4-fold elevated risk for NAFLD.
- Genetic correlation with liver disease risk. The research suggests a positive genetic correlation between liver MRI PDFF and liver disease risks, indicating a potential role of genetic factors in the development of these conditions. Liver MRI PDFF may act as a "transfer station" linking certain etiologic factors like high-density lipoprotein cholesterol, type 2 diabetes mellitus, and waist-to-hip ratio to liver diseases.
- Screening for liver diseases. Individuals with elevated liver MRI PDFF, even if they are asymptomatic or lack other risk factors, may benefit from screening for other liver diseases. This highlights the importance of timely assessment for liver disease risk in individuals with high MRI PDFF.
In an accompanying editorial, Scott B. Redder, M.D., Ph.D., and Jitka Starekova, M.D., emphasized the importance of timely liver disease risk assessment and the “strong evidence” from a large population data set demonstrating the association between liver MRI PDFF and liver diseases.
“These findings suggest that people with increased liver MRI PDFF may benefit from screening for other liver diseases, even if they are asymptomatic or do not have other risk factors,” maintained Drs. Redder and Starekova, who are affiliated with the Department of Radiology at the University of Wisconsin-Madison.
(Editor’s note: For related content, see “Can Deep Learning Enhance Ultrasound Assessment of Hepatic Steatosis in Patients with NAFLD?,” “Could Photon Counting CT Supplant MRI for Imaging Assessment of Hepatic Steatosis?” and “MRI Study Shows Higher Fibrosis Risk Among First-Degree Relatives of People with NAFLD and Advanced Fibrosis.”)
In regard to study limitations, the study authors acknowledge that the cohort was comprised entirely of people from European ancestry, limiting extrapolation of the study findings to a broader population. They also conceded the possibility that their findings may have been influenced by additional confounding factors that were not assessed in the study.