Discordance Between Metabolic Burden and Fibrosis Severity in Black Youth with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Document Type

Conference Proceeding

Publication Date

10-2026

Publication Title

Hepatology

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition in the pediatric population. Although racial and ethnic differences in pediatric MASLD prevalence are recognized, less is known about whether Black youth with MASLD differ in metabolic phenotype, genetic risk, or histologic severity. We compared metabolic and histologic features of Black and White pediatric participants enrolled in the NASH Clinical Research Network.

Methods: We analyzed baseline characteristics of 1,248 pediatric participants (mean age 12.5 years) enrolled in the NASH CRN. Participants were categorized as non-Hispanic Black (NHB, n=21), Hispanic Black (HB, n=20), non-Hispanic White (NHW, n=306), or Hispanic White/Other (HW/Other, n=901). Clinical, metabolic, PNPLA3 genotype, and centrally reviewed liver histology data were compared across groups. Logistic regression evaluated the association of race/ethnicity with clinically significant fibrosis, defined as stage 2–4 versus stage 0–1.

Results: NHB participants had the highest mean weight, BMI z-score, and prevalence of severe obesity; severe obesity was present in 67% of NHB participants compared with 41% of NHW and 25% of HW/Other participants (p< 0.001). Metabolic syndrome was significantly more prevalent in NHB and HB cohorts (45% for both) compared to HW (29%; p< 0.001). NHB also demonstrated the highest levels of insulin resistance (HOMA-IR median 8.8 vs 5.2 NHW, p>0.001). Triglyceride levels were significantly lower in NHB vs. NHW children (median 116 vs. 140; p=0.006). PNPLA3 risk genotype frequency differed substantially across groups: 36% of NHB participants carried the CG/GG genotype compared with 72% of NHW and 92% of HW/Other participants (p< 0.001). On biopsy, NAS and fibrosis scores did not differ between NHB and NHW children. (NAS 4.4 vs 4.2 p = 0.44) and fibrosis stage 0.8 vs 1.2, p = 0.18). Multivariable logistic regression analysis showed that NHB and HB participants had a lower odds of clinically significant fibrosis compared to NHW, adjusted for age, sex, BMI z-score, Type 2 diabetes, hypertension, and triglyceride level (OR=0.29 [95% CI 0.11, 0.77], p=0.01), but this association was attenuated when adjusted for PNPLA3 genotype (OR=0.35 [95% CI 0.11, 1.04), p=0.06).

Conclusion: Black youth with MASLD in the NASH CRN had greater obesity, and insulin resistance, but did not have greater histologic severity than White youth. Lower PNPLA3 risk genotype frequency may partly explain the lower adjusted odds of clinically significant fibrosis observed in Black participants. These findings illustrate heterogeneity in pediatric MASLD and support further study of how metabolic, genetic, and social determinants jointly shape disease severity across racial and ethnic groups.

Volume

84

Issue

Suppl 1

First Page

s1353

Comments

American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 5-9, 2026, Denver, CO

Helen DeVos Children's Hospital

Last Page

s1354

DOI

10.1097/01.HEP.0001249256.48215.72

ISSN

1527-3350

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