Medical therapy of MASLD – consequences of the paradigm shift from histology to non-invasive tests
Abstract
BACKGROUND & AIMS: The recent approval of pharmacological therapies for fibrotic metabolic dysfunction-associated steatohepatitis (MASH) has increased the need for accurate identification of treatment-eligible patients. Current recommendations increasingly rely on non-invasive tests (NITs), including vibration-controlled transient elastography (VCTE), while multiparametric ultrasound (MPUS) may provide additional opportunities for non-invasive assessment. However, agreement between histology and imaging-based approaches remains uncertain. We compared treatment eligibility based on histology, VCTE, and MPUS in two international biopsy-proven cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We analysed two biopsy-proven MASLD cohorts: CAP-IPDMA (n=1029), including VCTE and controlled attenuation parameter (CAP), and iLEAD (n=124), including MPUS. Treatment eligibility was assessed using histologically confirmed F2/F3 MASH and NIT-based recommendations from international expert panels. RESULTS: In CAP-IPDMA, 277/1029 patients (26.9%) met the histological definition of "at-risk MASH". Depending on the VCTE cut-off, 13.2-32.0% qualified for treatment. Overlap between histological "at-risk MASH" and VCTE thresholds was limited, reaching 27.8% when using VCTE 8-15 kPa, and decreasing when narrower or higher thresholds were applied. Among patients identified only by VCTE 8-15 kPa, males had lower median AST and ALT than those fulfilling only the histological indication (35 vs 48 IU/L p=0.034 and 45 vs 62 IU/L p=0.0072, respectively). In iLEAD, 21/124 patients (16.9%) met the histological definition, while 13.7-16.1% were eligible based on SWE thresholds, again with a similarly limited overlap. CONCLUSIONS: Histology and non-invasive tests capture partly distinct patient populations, meaning that both the number and type of patients selected for therapy depend on the chosen modality and cutoffs. As vibration-controlled transient elastography and multiparametric ultrasound become increasingly accessible in clinical practice, prospective validation is essential for establishing reliable non-invasive treatment pathways. IMPACT AND IMPLICATIONS: The current literature reflects a paradigm shift away from biopsy-based approaches toward NIT-based assessment of treatment eligibility in metabolic dysfunction-associated steatotic liver disease (MASLD), which may substantially affect which patients receive newly approved therapies. Our results are important for clinicians, researchers, and guideline developers because histology and current NIT cut-offs identify only partially overlapping patient populations, implying that different diagnostic strategies select different risk profiles. In practice, these findings support thoughtful implementation of NIT-based treatment pathways, the use of repeated measurements, and prospective validation of NIT thresholds to guide clinical care, trial design, and health policy decisions.
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BibTeX
@article{messer2026medical,
title = {{Medical therapy of MASLD – consequences of the paradigm shift from histology to non-invasive tests}},
author = {Eva Katharina Messer and David Petroff and Katsutoshi Sugimoto and Philip Newsome and Fuminori Moriyasu and Shalimar Shalimar and Marco Dioguardi Burgio and Cosmin Sebastian Voican and Valérie Vilgrain and Victor de Lédinghen and Daniel Jesper and Stephan Baumeler and Deike Strobel and Wah Kheong Chan and Edward Grant and Gabriel Perlemuter and Linda Kelahan and Ana-Carolina Cardoso and Helena Gabriel and Sandeep Aggarwal and Byung Ihn Choi and Peter Eddowes and Takashi Nishimura and Michael Allison and Hiroko Iijima and Emmanuel Tsochatzis and Theodore Dubinsky and Quentin Anstee and Jing Gao and David Sheridan and Dong Ho Lee and Jeremy Cobbold and Jae Young Lee and Sylvie Naveau and Yanan Zhao and David Semela and Pintong Huang and Grace Lai-Hung Wong and Jie Zeng and Vincent Wai-Sun Wong and Adrian Lim and Cristiane Villela-Nogueira and Xiaoyan Xie and Harshit Garg and Richard Barr and Vito Cantisani and Giovanna Ferraioli and Kentaro Sakamaki and Takao Itoi and Masayoshi Kage and Hirohisa Yano and Valentin Blank and Johannes Wiegand and Thomas Karlas},
journal = {JHEP Reports Innovation in Hepatology},
year = {2026},
month = oct,
doi = {10.1016/j.jhepr.2026.101996},
url = {https://hal.science/hal-05793480v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Medical therapy of MASLD – consequences of the paradigm shift from histology to non-invasive tests
AU - Eva Katharina Messer
AU - David Petroff
AU - Katsutoshi Sugimoto
AU - Philip Newsome
AU - Fuminori Moriyasu
AU - Shalimar Shalimar
AU - Marco Dioguardi Burgio
AU - Cosmin Sebastian Voican
AU - Valérie Vilgrain
AU - Victor de Lédinghen
AU - Daniel Jesper
AU - Stephan Baumeler
AU - Deike Strobel
AU - Wah Kheong Chan
AU - Edward Grant
AU - Gabriel Perlemuter
AU - Linda Kelahan
AU - Ana-Carolina Cardoso
AU - Helena Gabriel
AU - Sandeep Aggarwal
AU - Byung Ihn Choi
AU - Peter Eddowes
AU - Takashi Nishimura
AU - Michael Allison
AU - Hiroko Iijima
AU - Emmanuel Tsochatzis
AU - Theodore Dubinsky
AU - Quentin Anstee
AU - Jing Gao
AU - David Sheridan
AU - Dong Ho Lee
AU - Jeremy Cobbold
AU - Jae Young Lee
AU - Sylvie Naveau
AU - Yanan Zhao
AU - David Semela
AU - Pintong Huang
AU - Grace Lai-Hung Wong
AU - Jie Zeng
AU - Vincent Wai-Sun Wong
AU - Adrian Lim
AU - Cristiane Villela-Nogueira
AU - Xiaoyan Xie
AU - Harshit Garg
AU - Richard Barr
AU - Vito Cantisani
AU - Giovanna Ferraioli
AU - Kentaro Sakamaki
AU - Takao Itoi
AU - Masayoshi Kage
AU - Hirohisa Yano
AU - Valentin Blank
AU - Johannes Wiegand
AU - Thomas Karlas
PY - 2026
DA - 2026/10/12
JO - JHEP Reports Innovation in Hepatology
DO - 10.1016/j.jhepr.2026.101996
UR - https://hal.science/hal-05793480v1
AB - BACKGROUND & AIMS: The recent approval of pharmacological therapies for fibrotic metabolic dysfunction-associated steatohepatitis (MASH) has increased the need for accurate identification of treatment-eligible patients. Current recommendations increasingly rely on non-invasive tests (NITs), including vibration-controlled transient elastography (VCTE), while multiparametric ultrasound (MPUS) may provide additional opportunities for non-invasive assessment. However, agreement between histology and imaging-based approaches remains uncertain. We compared treatment eligibility based on histology, VCTE, and MPUS in two international biopsy-proven cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We analysed two biopsy-proven MASLD cohorts: CAP-IPDMA (n=1029), including VCTE and controlled attenuation parameter (CAP), and iLEAD (n=124), including MPUS. Treatment eligibility was assessed using histologically confirmed F2/F3 MASH and NIT-based recommendations from international expert panels. RESULTS: In CAP-IPDMA, 277/1029 patients (26.9%) met the histological definition of "at-risk MASH". Depending on the VCTE cut-off, 13.2-32.0% qualified for treatment. Overlap between histological "at-risk MASH" and VCTE thresholds was limited, reaching 27.8% when using VCTE 8-15 kPa, and decreasing when narrower or higher thresholds were applied. Among patients identified only by VCTE 8-15 kPa, males had lower median AST and ALT than those fulfilling only the histological indication (35 vs 48 IU/L p=0.034 and 45 vs 62 IU/L p=0.0072, respectively). In iLEAD, 21/124 patients (16.9%) met the histological definition, while 13.7-16.1% were eligible based on SWE thresholds, again with a similarly limited overlap. CONCLUSIONS: Histology and non-invasive tests capture partly distinct patient populations, meaning that both the number and type of patients selected for therapy depend on the chosen modality and cutoffs. As vibration-controlled transient elastography and multiparametric ultrasound become increasingly accessible in clinical practice, prospective validation is essential for establishing reliable non-invasive treatment pathways. IMPACT AND IMPLICATIONS: The current literature reflects a paradigm shift away from biopsy-based approaches toward NIT-based assessment of treatment eligibility in metabolic dysfunction-associated steatotic liver disease (MASLD), which may substantially affect which patients receive newly approved therapies. Our results are important for clinicians, researchers, and guideline developers because histology and current NIT cut-offs identify only partially overlapping patient populations, implying that different diagnostic strategies select different risk profiles. In practice, these findings support thoughtful implementation of NIT-based treatment pathways, the use of repeated measurements, and prospective validation of NIT thresholds to guide clinical care, trial design, and health policy decisions.
SN - 2589-5559
ER -