Noninvasive Imaging Tools Fall Short for High-Grade Fibrosis Detection in Pediatric MASLD

Naseem Ravanbakhsh, MD

Credit: AASLD

New research suggests magnetic resonance elastography (MRE) and transient elastography (TE) may not be proficient for predicting high-grade fibrosis in pediatric patients with metabolic dysfunction-associated steatotic liver disease (MASLD) when compared to liver biopsy.¹

Although both MRE and TE failed to accurately predict high-grade fibrosis on liver biopsy with no statistically significant differences between the 2 noninvasive imaging modalities, the area under the receiver operating characteristic curves (AUROC) for MRE was slightly superior to that of TE.¹

“As MASLD and MASH become an ever-growing diagnosis in pediatrics, it is imperative to find noninvasive modalities that can reliably monitor disease progression,” Naseem Ravanbakhsh, MD, of the department of pediatric gastroenterology, hepatology, and nutrition at Children's Hospital Los Angeles, and colleagues wrote.¹ “As new and emerging therapies become available to this population, these tools will help clinicians monitor disease prevalence and progression more effectively. TE and MRE are newer and imprecise modalities and may serve as a guide, though there is a need for longitudinal monitoring to better answer which form of technology has greater reliability.”

A leading cause of liver disease among children, MASLD affects up to 38% of children with obesity in the United States, although not all children with MASLD have obesity. If left untreated, MASLD can lead to cirrhosis and liver failure, underscoring the importance of prompt identification with liver biopsy and/or noninvasive imaging tools and subsequent treatment.²

To investigate and compare the predictive accuracy of MRE and TE for detecting high-grade fibrosis on liver biopsy, investigators conducted a retrospective chart review of children 9-18 years of age with liver biopsy-proven MASLD at Children's Hospital Los Angeles between September 2017 and January 2023. They noted the current practice in their clinic is to recommend baseline MRE and TE at the time of liver biopsy, followed by periodic monitoring with MRE or TE, or both over the treatment course, directed by the clinical indications and correlation to liver biopsy.¹

To evaluate and compare the predictive accuracy of MRE and TE for identifying high-grade fibrosis, investigators dichotomized results based on established thresholds into “low-grade fibrosis” and “high-grade fibrosis.” For MRE and TE, “high-grade fibrosis” measures were kPa ≥ 3.05 and kPa ≥ 9, respectively, and “high-grade fibrosis,” as determined by liver biopsy (Metavir Stages 3 and 4) served as the reference standard for calculating the AUROC as a summary measure of diagnostic accuracy for both MRE and TE.¹

Among an initial cohort of 455 patients who had undergone TE, 356 were excluded for not having undergone all 3 studies (liver biopsy, MRE, and TE). Specifically, 34 patients had only liver biopsy and TE available, 81 patients only had MRE and TE available, and 241 patients only had TE available. An additional 22 patients were excluded for having an alternative diagnosis other than MASLD, resulting in 77 patients in the final study cohort.¹

Among these patients, the median age was 14 years, 57% of patients were male, and 64% were of Hispanic ethnicity. Investigators noted the most frequent comorbidities were obesity (100%), dyslipidemia (19%), and type 2 diabetes (21%).¹

Based on liver biopsy results, 40% of patients had Grade 1 steatosis (5%–33% steatosis), 47% had Grade 2 steatosis (34%–66% steatosis), and 13% had Grade 3 steatosis (>66% steatosis). Additionally, 13% of the study population was classified as NAS 3, 39% as NAS 4, and 38% as NAS 5. Investigators identified fibrosis in 90% of liver biopsies, primarily Metavir Stages 1 and 2.¹

The TE median controlled attenuation parameter (CAP) was 346 dB/m and the median kPa was 8.4. The median Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) was 22% and the median kPa was 2.1. Of note, the AUROC curves of MRE and TE for the detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not statistically significantly different (P = .4785).¹

Investigators acknowledged multiple limitations to these findings, including the single-center study design and specialized setting limiting generalizability; the potential for selection bias due to many patients undergoing liver biopsy when they have more advanced disease; the lack of consideration for longitudinal elastography and hepatic steatosis; and the risk for type II error due to the small sample sizes.¹

“Our study demonstrates that MRE and TE, two noninvasive imaging modalities, are not proficient in predicting high-grade fibrosis when compared to liver biopsy, although MRE performed better than TE based on AUROC,” investigators concluded.¹ “Our AUROC findings are modest, suggesting that interpretation should be made with caution. This does not provide generalizable recommendations but does highlight the need for further studies in this group that optimizes sample size and diversity of patient types.”

References

1. ^{Ravanbakhsh N, Browne D, Weaver C, et al. Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1002/jpn3.12368}
2. ^{Mayo Clinic. Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). October 4, 2023. Accessed September 23, 2024. https://www.mayoclinic.org/medical-professionals/pediatrics/news/pediatric-metabolic-dysfunction-associated-steatotic-liver-disease-masld-formerly-known-as-nonalcoholic-fatty-liver-disease-nafld/mac-20555493}