Alkhouri, Naim;
Akbary, Kutbuddin;
Ren, Yayun;
Naoumov, Nikolai;
Chng, Elaine;
Tai, Dean;
Brees, Dominique;
(2024)
Comparative Evaluation of Zonal Fibrosis Patterns in Pediatric and Adult Metabolic Dysfunction-associated Steatohepatitis Biopsies Using Second Harmonic Generation/two Photon Excitation-based qFibrosis Analysis.
Presented at: AASLD The Liver Meeting, San Diego, California, USA.
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Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent among children, constituting the most common chronic liver ailment. Prior studies of liver biopsies from pre-adolescent children with metabolic dysfunction-associated steatohepatitis (MASH) identified an alternate pattern characterized by zone 1 centered steatosis, inflammation, and fibrosis, usually without ballooning, which may progress to advanced fibrosis. The aim of this study was to evaluate pediatric MASH biopsies using Second Harmonic Generation (SHG)/Two-Photon Excitation (TPE) microscopy and Artificial Intelligence (AI) analysis and compare the fibrosis patterns and distribution with biopsies from adults with MASH. // Methods: Nine unstained biopsies from children (aged 8 to 16 years) with MASH underwent SHG/TPE and AI analysis, yielding qFibrosis continuous values categorized into qFibrosis stages, based on pre-defined cut-offs. Biopsies were segregated into early (qF0/qF1/qF2; n=3) and advanced (qF3/qF4; n=6) fibrosis groups. Comparative analysis involved an adult cohort from a MASH clinical trial (NCT02855164), similarly categorized into early (n=96) and advanced (n=60) fibrosis stages. Fibrosis distribution in both cohorts was plotted on radar maps illustrating portal; periportal; perisinusoidal (zone 2), pericentral and central vein fibrosis, with zonal differences statistically significant at p≤0.05 by Spearman test. // Results: In the early fibrosis groups, pediatric biopsies exhibited significantly greater perisinusoidal (PS) (p=0.03) and more portal fibrosis compared to adults. In advanced fibrosis groups, pediatric biopsies demonstrated significantly less portal fibrosis (p=0.02) along with markedly increased PS fibrosis (p=0.01) compared to adult biopsies. Additionally, pediatric biopsies in advanced fibrosis group had more fibrosis in periportal (PP) and pericentral (PC) regions compared to adult biopsies. // Conclusion: This quantitative digital evaluation of MASH fibrosis highlights significant differences in zonal fibrosis distribution in pediatric MASH biopsies compared to adults. During the early fibrosis stage, pediatric biopsies show increased perisinusoidal and portal fibrosis in contrast to their adult counterparts. At advanced stages, there is significantly less portal fibrosis in pediatric biopsies compared to adults, although perisinusoidal fibrosis remains significantly greater in the pediatric group. The observed differences in fibrosis patterns hold potential implications for accurate assessment of fibrosis regression in pediatric MASH clinical trials.
| Type: | Poster |
|---|---|
| Title: | Comparative Evaluation of Zonal Fibrosis Patterns in Pediatric and Adult Metabolic Dysfunction-associated Steatohepatitis Biopsies Using Second Harmonic Generation/two Photon Excitation-based qFibrosis Analysis |
| Event: | AASLD The Liver Meeting |
| Location: | San Diego, California, USA |
| Dates: | Oct 2024 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/HEP.0000000000001077 |
| Publisher version: | https://doi.org/10.1097/hep.0000000000001077 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203683 |
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