Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease

Park, Charlie C.; Nguyen, Phirum; Hernandez, Carolyn; Bettencourt, Ricki; Ramirez, Kimberly; Fortney, Lynda; Hooker, Jonathan; Sy, Ethan; Alquiraish, Mosab; Valasek, Mark A.; Rizo, Emily; Richards, Lisa; Brenner, David A.; Sirlin, Claude B.; Loomba, Rohit

doi:10.1016/s0016-5085(17)30587-5

Cited by 70 publications

(109 citation statements)

References 38 publications

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“…Although changes in liver stiffness by FibroScan were not significant, this may reflect the reduced precision and accuracy of FibroScan in obese patients. (44) This randomized trial assessed changes in liver fat content by MRI-PDFF and liver stiffness by MRE, along with liver biopsy assessments before and after treatment, with results assessed by central reviewers blinded to treatment assignments. Liver fibrosis on histology was assessed using a comprehensive set of parameters including NASH CRN fibrosis stage, quantitative digital morphometry, and a-SMA immunostaining before and after treatment.…”

Section: Discussionmentioning

confidence: 99%

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

et al. 2017

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Inhibition of apoptosis signal–regulating kinase 1, a serine/threonine kinase, leads to improvement in inflammation and fibrosis in animal models of nonalcoholic steatohepatitis. We evaluated the safety and efficacy of selonsertib, a selective inhibitor of apoptosis signal–regulating kinase 1, alone or in combination with simtuzumab, in patients with nonalcoholic steatohepatitis and stage 2 or 3 liver fibrosis. In this multicenter phase 2 trial, 72 patients were randomized to receive 24 weeks of open‐label treatment with either 6 or 18 mg of selonsertib orally once daily with or without once‐weekly injections of 125 mg of simtuzumab or simtuzumab alone. The effect of treatment was assessed by paired pretreatment and posttreatment liver biopsies, magnetic resonance elastography, magnetic resonance imaging–estimated proton density fat fraction, quantitative collagen content, and noninvasive markers of liver injury. Due to the lack of effect of simtuzumab on histology or selonsertib pharmacokinetics, selonsertib groups with and without simtuzumab were pooled. After 24 weeks of treatment, the proportion of patients with a one or more stage reduction in fibrosis in the 18‐mg selonsertib group was 13 of 30 (43%; 95% confidence interval, 26‐63); in the 6‐mg selonsertib group, 8 of 27 (30%; 95% confidence interval, 14‐50); and in the simtuzumab‐alone group, 2 of 10 (20%; 95% confidence interval, 3‐56). Improvement in fibrosis was associated with reductions in liver stiffness on magnetic resonance elastography, collagen content and lobular inflammation on liver biopsy, as well as improvements in serum biomarkers of apoptosis and necrosis. There were no significant differences in adverse events between the treatment groups. Conclusion: These findings suggest that selonsertib may reduce liver fibrosis in patients with nonalcoholic steatohepatitis and stage 2‐3 fibrosis. (Hepatology 2018;67:549‐559).

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Section: Discussionmentioning

confidence: 99%

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

et al. 2017

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“…VCTE is inexpensive and can be measured in the clinic but has inferior diagnostic performance in head-to-head comparison studies with MRE, particularly for lower stages of fibrosis and in the morbidly obese. (12)(13)(14) In contrast to liver biopsy, MRE evaluates a much larger volume of the total liver (~5%), is reproducible, (15) and has high interobserver agreement. (16) While cross-sectional studies have demonstrated that MRE has superior diagnostic performance in NAFLD, there are limited longitudinal data on the association between changes in MRE and liver fibrosis on paired liver biopsies.…”

Section: Clinical Utility Of An Increase In Magnetic Resonance Elastomentioning

confidence: 99%

“…(29)(30)(31)(32)(33) Liver stiffness was estimated using two-dimensional MRE, which is the most accurate biomarker for the quantitative assessment of liver stiffness as a surrogate for hepatic fibrosis. (13,14,34) A passive driver was fitted around the body over the liver and connected to an acoustic active driver that delivered continuous vibrations at 60 Hz to produce shear waves in the liver, which were processed to generate elastograms depicting liver stiffness. Four slices were assessed, and colocalized regions of interest were manually specified.…”

Section: Mrimentioning

confidence: 99%

Clinical Utility of an Increase in Magnetic Resonance Elastography in Predicting Fibrosis Progression in Nonalcoholic Fatty Liver Disease

et al. 2020

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Background and Aims Cross‐sectional studies have shown that magnetic resonance elastography (MRE) is accurate in the noninvasive detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD). However, there are limited data on the longitudinal association between an increase in liver stiffness on MRE and fibrosis progression in NAFLD. Therefore, using a well‐characterized prospective cohort of patients with biopsy‐proven NAFLD, we aimed to examine the longitudinal association between a 15% increase in liver stiffness on MRE and fibrosis progression in NAFLD. Approach and Results This prospective cohort study included 102 patients (62.7% women) with biopsy‐proven NAFLD who underwent contemporaneous MRE and liver biopsy at baseline followed by a repeat paired liver biopsy and MRE assessment. The primary outcome was odds of fibrosis progression by one or more stage as assessed by the Nonalcoholic Steatohepatitis Clinical Research Network histologic scoring system. The mean (±SD) of age and body mass index (BMI) were 52 (±14) years and 32.6 (±5.3) kg/m2, respectively. The median time interval between the two paired assessments was 1.4 years (interquartile range 2.15 years). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 27, 36, 12, 17, and 10, respectively. In unadjusted analysis, a 15% increase in MRE was associated with increased odds of histologic fibrosis progression (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.17‐10.76; P = 0.0248). These findings remained clinically and statistically significant even after multivariable adjustment for age, sex, and BMI (adjusted OR, 3.36; 95% CI, 1.10‐10.31; P = 0.0339). A 15% increase in MRE was the strongest predictor of progression to advanced fibrosis (OR, 4.90; 95% CI, 1.35‐17.84; P = 0.0159). Conclusions A 15% increase in liver stiffness on MRE may be associated with histologic fibrosis progression and progression from early fibrosis to advanced fibrosis.

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“…(17) MRE has emerged as the most accurate tool to predict hepatic fibrosis, with an area under the receiver operating characteristic curve above 0.90 for all fibrosis stages (18,19) and higher accuracy than ultrasound-based elastography techniques (such as transient elastography or acoustic radiation force impulse elastography) for the detection of fibrosis in NAFLD. (20)(21)(22)(23) MRE has several advantages over ultrasound-based elastography, as it samples a much larger volume of the liver, is not affected by body mass index (24,25) or degree of steatosis, (14) is not operator-dependent, (26) has favorable test-retest repeatability, (26) and has a high success rate. (25,27) MRE estimates liver stiffness, which correlates to the amount of collagen deposition in the extracellular matrix, but liver stiffness is also influenced by other factors, such as inflammation, vascular congestion, and cholestasis.…”

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The Role of Three‐Dimensional Magnetic Resonance Elastography in the Diagnosis of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery

et al. 2019

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The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three‐dimensional magnetic resonance elastography (3D‐MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D‐MRE (mf3D‐MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI‐PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D‐MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D‐MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI‐PDFF correlated with steatosis (P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross‐validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross‐validated AUROC = 0.82. Conclusion: The mf3D‐MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.

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Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease

Cited by 70 publications

References 38 publications

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

Clinical Utility of an Increase in Magnetic Resonance Elastography in Predicting Fibrosis Progression in Nonalcoholic Fatty Liver Disease

The Role of Three‐Dimensional Magnetic Resonance Elastography in the Diagnosis of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery

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