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Fact Sheet: Liver Fat Does Not Affect Liver Stiffness Measured with MR Elastography


KEY TAKEAWAY

The presence of liver fat does not reduce liver stiffness measured by MRE. Multiple published studies report that hepatic steatosis does not systematically affect MRE-measured liver stiffness in patients with chronic liver disease. MRE is recognized as the most reliable non-invasive diagnostic test for detecting and staging liver fibrosis.

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Background

MR elastography (MRE) has emerged as the most reliable non-invasive diagnostic technology for detecting and staging liver fibrosis [1-2]. Among the histologic processes associated with chronic liver disease (fibrosis, inflammation, steatosis, and cell injury), the presence and severity of fibrosis is by far the strongest predictor of subsequent morbidity and mortality [3]. MRE measures the stiffness of liver tissue, which increases progressively with the severity of liver fibrosis. Diagnostic interpretation of MRE results should consider the fact that other processes such as chronic inflammation and hepatic venous congestion can also cause increased liver stiffness. Fortunately, these effects are modest and multiple studies have demonstrated that MRE has a diagnostic performance that rivals liver biopsy for assessing liver fibrosis [3]. Abnormal accumulation of lipid droplets in hepatocytes is a hallmark of nonalcoholic fatty liver disease (NAFLD), which has become one of the most important causes of fibrosis and end stage liver disease, world-wide [4]. Subcutaneous fat is very soft to palpation. So, is it possible that the presence of liver fat might reduce liver stiffness and thereby impair the ability of MRE to detect co-existing fibrosis?

Evidence in the literature

Multiple published studies have reported that hepatic steatosis does not systematically affect MRE-measured liver stiffness in patients with chronic liver disease [5-8]. Liver stiffness was significantly correlated with inflammation grade and fibrosis stage, but not with relative fat fraction [6]. Liver stiffness assessed by MRE had high accuracy (AUROC = 0.93) for discriminating patients with NASH from simple steatosis [6]. Longitudinal studies have measured liver fat and liver stiffness in subjects over time. In a recent clinical trial, the effectiveness of a therapeutic agent designed to reduce liver fat was tested in subjects with NAFLD [8]. The results demonstrated a significant reduction in liver fat by more than 30% in treated subjects, as measured my proton density fat fraction MRI. However no significant change in liver stiffness was observed with MRE, supporting the principle that liver fat has little influence on liver tissue stiffness [8].

Alternate Findings

There is evidence that ultrasound-based elastography measurements of liver stiffness are affected by liver fat [9-10]. This is likely an artifactual effect, arising from a physical phenomenon known as called dispersion [11]. In a small number of publications, a correlation between liver stiffness and steatosis was found. In a study of 327 patients with chronic hepatitis C, liver stiffness was correlated to viral activity and steatosis following a univariate analysis. However, fibrosis stage was also correlated to activity and steatosis. When performing the multivariate analysis including fibrosis, activity, and steatosis, fibrosis was the only parameter that significantly correlated to liver stiffness [12]. One study concluded that “liver volume, fat fraction, and stiffness are inter-related and associated with multiple patient-specific factors” in a pediatric cohort of 202 patients [13]. The authors state “for every 1% increase in liver fat fraction, there was a 0.02 kPa decrease in liver stiffness.” If a patient experienced a 10% increase in liver fat fraction with baseline liver stiffness of 3.5 kPa, this would be a 0.2 kPa decrease in liver stiffness, or an overall percent decrease of 6%. This falls well below the QIBA guideline of a 19% change or larger indicates a true change in stiffness has occurred with 95% confidence [14].

Conclusion

The preponderance of literature evidence supports a conclusion that MRE-based measurements of liver stiffness are not significantly affected by liver steatosis [5-8].

References

[1] S. Singh et al., “Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled,” Eur Radiol, 2016. 26:1431–1440.

[2] H. Morisaka et al., “Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.” J Magn Reason Imaging. 2018. 47:1268-1275.

[3] M. Ekstedt et al., “Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up,” Hepatol. 2015. 61(5):1547–1554.

[4] M. Benedict and X. Zhang., “Non-alcoholic fatty liver disease: An expanded review,” World J Hepatol., 2017. 9(16):715–732.

[5] M. Yin et al., “A Preliminary Assessment of Hepatic Fibrosis with Magnetic Resonance Elastography,” Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc., 2007. 5(10):1207-1213.

[6] J. Chen, J. A. Talwalkar, M. Yin, K. J. Glaser, S. O. Sanderson, and R. L. Ehman, “Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography.,” Radiology, 2011. 259(3):749–756.

[7] H. S. Leitão et al., “Hepatic Fibrosis, Inflammation, and Steatosis: Influence on the MR Viscoelastic and Diffusion Parameters in Patients with Chronic Liver Disease,” Radiology, 2017. 283(1):98–107.

[8] R. Loomba et al., “GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease,” Gastroenterology, 2018. 155(5):1463-1473.e6.

[9] M. Friedrich-Rust et al, “Acoustic radiation force impulse-imaging and transient elastography for non-invasive assessment of liver fibrosis and steatosis in NAFLD,” Eur J Radiol, 2012. 81:325–331.

[10] C. C. Park et al., “Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease,” Gastroenterology, 2017. 152(3):598-607.

[11] C.T. Barry et al., “Shear wave dispersion measures liver steatosis,” Ultrasound Med Biol, 2012. 38(2):175-182.

[12] M. Ziol et al., “Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C,” Hepatol. 2005. 41(1):48–54.

[13] M. Joshi et al., “Quantitative MRI of fatty liver disease in a large pediatric cohort: correlation between liver fat fraction, stiffness, volume, and patient-specific factors,” Abdom. Radiol. 2018. 43(5):1168–1179.

[14] QIBA MR Elastography of the Liver Biomarker Committee. Magnetic Resonance Elastography of the Liver. Profile Stage: Consensus. QIBA, May 2, 2018. Available from: http://qibawiki.rsna.org/index.php/Profiles


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