In the Journals

NASH study validates liver stiffness by MRE, MRI-PDFF as viable biomarkers

Liver stiffness measurements by magnetic resonance elastography and magnetic resonance imaging-proton density fat fraction demonstrated continued feasibility as biomarkers of liver fibrosis in a recently published study.

“Widespread screening is not currently feasible given that a definitive diagnosis of NASH can only be made through identification of the characteristic histopathologic pattern on liver biopsy. While liver biopsy remains the gold-standard, its disadvantages are well known,” Saumya Jayakumar, MD, from the University of California in San Diego, and colleagues wrote. “There is a pressing unmet medical need for reliable and accurate noninvasive tools to evaluate steatosis and fibrosis in patients with NASH, and to monitor response to treatment.”

The study comprised 72 patients with biopsy-proven NASH and stage 2 or 3 fibrosis, of whom 54 had available MRE results and 65 had available MRI-PDFF results at both baseline and week 24.

At baseline, liver stiffness by MRE correlated significantly with fibrosis stage (r = 0.33; P = .007), liver stiffness by Echosens’ FibroScan (r = 0.49; P < .001), hepatic alpha-smooth muscle actin expression (r = 0.29; P = .02), and Enhanced Liver Fibrosis test (r = 0.25; P = .045). At week 24, MRE liver stiffness measurements correlated significantly with the factors as well as hepatic collagen content by morphometry (P .001).

Liver stiffness by MRE demonstrated an AUROC of 0.8 (95% CI, 0.68-0.92) at week 24 for the discrimination between early fibrosis stages and advanced fibrosis. However, the AUROCs for predicting nonalcoholic fatty liver disease activity score (NAS) response (0.66; 95% CI, 0.48-0.83), predicting fibrosis improvement (0.62; 95% CI 0.46-0.78), and detecting fibrosis progression (0.57; 95% CI, 0.36-0.79) were much lower.

MRI-PDFF results correlated significantly with hepatic fat content at baseline (r = 0.61; P < .001) and 24 weeks (r = 0.87; P < .001) and with NAS steatosis grade at baseline (r = 0.57; P < .001) and 24 weeks (r = 0.59; P < .001).

The AUROCs of MRI-PDFF were both 0.7 for the prediction of steatosis improvement (95% CI, 0.57-0.83) and the prediction of NAS response (95% CI, 0.51-0.89).

“Cross-sectional studies have consistently shown a correlation between MRE and histologic fibrosis stage, while longitudinal studies are lacking,” the researchers wrote. “MRE has been shown to be more accurately discriminate advanced fibrosis compared with earlier stages; our results support these findings. MRI-PDFF has been repeatedly shown to correlate strongly with hepatic fat assessed histologically. For future studies, the threshold of MRE reduction deemed clinically relevant could be optimized to maximize sensitivity or specificity as appropriate.” – by Talitha Bennett

Disclosure: Jayakumar reports she is on the speakers bureau for Astellas and Gilead and has received grants from Bristol-Myers Squibb. Please see the full study for the other authors’ relevant financial disclosures.

Liver stiffness measurements by magnetic resonance elastography and magnetic resonance imaging-proton density fat fraction demonstrated continued feasibility as biomarkers of liver fibrosis in a recently published study.

“Widespread screening is not currently feasible given that a definitive diagnosis of NASH can only be made through identification of the characteristic histopathologic pattern on liver biopsy. While liver biopsy remains the gold-standard, its disadvantages are well known,” Saumya Jayakumar, MD, from the University of California in San Diego, and colleagues wrote. “There is a pressing unmet medical need for reliable and accurate noninvasive tools to evaluate steatosis and fibrosis in patients with NASH, and to monitor response to treatment.”

The study comprised 72 patients with biopsy-proven NASH and stage 2 or 3 fibrosis, of whom 54 had available MRE results and 65 had available MRI-PDFF results at both baseline and week 24.

At baseline, liver stiffness by MRE correlated significantly with fibrosis stage (r = 0.33; P = .007), liver stiffness by Echosens’ FibroScan (r = 0.49; P < .001), hepatic alpha-smooth muscle actin expression (r = 0.29; P = .02), and Enhanced Liver Fibrosis test (r = 0.25; P = .045). At week 24, MRE liver stiffness measurements correlated significantly with the factors as well as hepatic collagen content by morphometry (P .001).

Liver stiffness by MRE demonstrated an AUROC of 0.8 (95% CI, 0.68-0.92) at week 24 for the discrimination between early fibrosis stages and advanced fibrosis. However, the AUROCs for predicting nonalcoholic fatty liver disease activity score (NAS) response (0.66; 95% CI, 0.48-0.83), predicting fibrosis improvement (0.62; 95% CI 0.46-0.78), and detecting fibrosis progression (0.57; 95% CI, 0.36-0.79) were much lower.

MRI-PDFF results correlated significantly with hepatic fat content at baseline (r = 0.61; P < .001) and 24 weeks (r = 0.87; P < .001) and with NAS steatosis grade at baseline (r = 0.57; P < .001) and 24 weeks (r = 0.59; P < .001).

The AUROCs of MRI-PDFF were both 0.7 for the prediction of steatosis improvement (95% CI, 0.57-0.83) and the prediction of NAS response (95% CI, 0.51-0.89).

“Cross-sectional studies have consistently shown a correlation between MRE and histologic fibrosis stage, while longitudinal studies are lacking,” the researchers wrote. “MRE has been shown to be more accurately discriminate advanced fibrosis compared with earlier stages; our results support these findings. MRI-PDFF has been repeatedly shown to correlate strongly with hepatic fat assessed histologically. For future studies, the threshold of MRE reduction deemed clinically relevant could be optimized to maximize sensitivity or specificity as appropriate.” – by Talitha Bennett

Disclosure: Jayakumar reports she is on the speakers bureau for Astellas and Gilead and has received grants from Bristol-Myers Squibb. Please see the full study for the other authors’ relevant financial disclosures.