MASH Resolution Index: development and validation of a non-invasive score to detect histological resolution of MASH
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Background: Dynamic changes in non-invasive tests, such as changes in alanine aminotransferase (ALT) and MRI proton-density-fat-fraction (MRI-PDFF), may help to detect metabolic dysfunction-associated steatohepatitis (MASH) resolution, but a combination of non-invasive tests may be more accurate than either alone. We developed a novel non-invasive score, the MASH Resolution Index, to detect the histological resolution of MASH. Methods: This study included a derivation cohort of 95 well-characterised adult participants (67% female) with biopsy-confirmed MASH who underwent contemporaneous laboratory testing, MRI-PDFF and liver biopsy at two time points. The primary objective was to develop a non-invasive score to detect MASH resolution with no worsening of fibrosis. The most predictive logistic regression model was selected based on the highest area under the receiver operating curve (AUC), and the lowest Akaike information criterion and Bayesian information criterion. The model was then externally validated in a distinct cohort of 163 participants with MASH from a clinical trial. Results: The median (IQR) age and body mass index were 55 (45–62) years and 32.0 (30–37) kg/m 2 , respectively, in the derivation cohort. The most accurate model (MASH Resolution Index) included MRI-PDFF, ALT and aspartate aminotransferase. The index had an AUC of 0.81 (95% CI 0.69 to 0.93) for detecting MASH resolution in the derivation cohort. The score calibrated well and performed robustly in a distinct external validation cohort (AUC 0.83, 95% CI 0.76 to 0.91), and outperformed changes in ALT and MRI-PDFF. Conclusion: The MASH Resolution Index may be a useful score to non-invasively identify MASH resolution.
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The MASH-RI was developed and validated from cohorts of patients with biopsy-proven MASH and liver fibrosis enrolled in MASH drug trials.
“the MASH Resolution Index (MASH-RI) was recently developed and validated from cohorts of patients with biopsy-proven MASH and liver fibrosis enrolled in MASH drug trials [21].”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
The Methods (Study design; page not provided) describe development and validation using two cohorts with biopsy-proven MASH. The validation cohort had stage 2 or 3 fibrosis and came from a drug trial, but the derivation cohort also included patients whose follow-up biopsy was part of standard medical care. The claim therefore overstates that both cohorts were enrolled in MASH drug trials. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAt the rule-out threshold (≤ -2.67), the MASH-RI achieved negative predictive values of 92.6% and 100%.
“At the rule-out threshold (≤ − 2.67), the MASH-RI achieved negative predictive values of 92.6% and 100%”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
The Results sections on diagnostic performance report an NPV of 93% in the derivation cohort and 100% in the validation cohort at the 90% sensitivity cut-point; 93% is consistent with the claimed 92.6% after rounding. The passages available in our copy do not give the specific rule-out threshold of ≤−2.67 or the unrounded 92.6% figure, so those details remain unsupported. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn the validation cohort, the PPV of the MASH-RI at the rule-in threshold (≥ -0.67) was 29.2%, outperforming ALT (23.7%) and MRI-PDFF (25.8%).
“In the validation cohort, the PPV of the MASH-RI at the rule-in threshold (≥ − 0.67) was 29.2%, which, while modest, outperformed other non-invasive biomarkers such as ALT (PPV 23.7%) and MRI-PDFF (PPV 25.8%).”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
The Results section on diagnostic performance in the validation cohort reports a 29% PPV at the rule-in cut-point. The Discussion (Strengths and limitations) says this outperformed ALT response (23.7%) and MRI-PDFF response (25.8%). Our copy does not give the claimed ≥−0.67 threshold or the more precise 29.2% PPV. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAt the rule-in threshold (≥ -0.67), the MASH-RI yielded specificities of 89.6% and 53.0%.
“the rule-in threshold (≥ − 0.67) yielded specificities of 89.6% and 53.0%”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
The Results sections on diagnostic performance report a rule-in cut-point and a derivation-cohort cut-point targeting 90% specificity. In the validation cohort, they report 90% sensitivity and a positive likelihood ratio of 1.9 at rule-in, consistent with roughly 53% specificity. The passages in our copy do not give the ≥−0.67 threshold or explicitly state the exact specificities of 89.6% and 53.0% (page numbers unavailable). (LLM, conf=0.77)
Experimental — accuracy not yet measuredThe MASH-RI combines ALT, AST, and MRI-PDFF to detect MASH resolution without a liver biopsy and offers better accuracy and precision than single biomarkers of response.
“The MASH-RI combines ALT, AST, and MRI-PDFF to detect MASH resolution without a liver biopsy and offers better accuracy and precision than single biomarkers of response [21].”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
In derivation and external validation cohorts, the MASH-RI demonstrated superior accuracy for detecting histologic MASH resolution, with AUCs of 0.81 and 0.83, respectively.
“In both derivation and external validation cohorts, the MASH-RI demonstrated superior accuracy for detecting histologic MASH resolution, with AUCs of 0.81 and 0.83, respectively.”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [21]
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MASLD: Spatial Mechanisms and New Therapeutics
Stoess, C., Onyuru, J., Hu, Y., Jiang, Y., Xin, Z., Panchal, A., & Hartmann, P. (2026) · Biomolecules · doi:10.3390/biom16081129
Huneault, H. E., Sudhakar, S. G., Gent, A., Jarrell, Z. R., Smith, M. R., Sanchez-Torres, C., Jain, A. K., Yates, K. P., Neuschwander‐Tetri, B. A., Schwimmer, J. B., et al. (2026) · JHEP Reports · doi:10.1016/j.jhepr.2026.102016
Self-citationMironova, M., Ratziu, V., Rinella, M. E., Bansal, M. B., Noureddin, M., Alkhouri, N., Anstee, Q. M., Newsome, P. N., Schattenberg, J. M., Sanyal, A. J., et al. (2026) · Gut · doi:10.1136/gutjnl-2026-340031
Self-citationNew perspectives in alleviating MASLD: synergism and prospects of exercise and natural products
Wu, Q., Li, J., Lin, B., Xu, H., & Chen, N. (2026) · Food Science and Human Wellness · doi:10.26599/fshw.2026.9251137
- Authors
- Loomba, R., Amangurbanova, M., Bettencourt, R., Madamba, E., Siddiqi, H., Richards, L., Behling, C., Sirlin, C. B., Gottwald, M. D., Feng, S., Margalit, M., & Huang, D. Q.
- Affiliations
- University of California San Diego (US)
- NAFLD Research Center, University of California, La Jolla, California, USA
- University of California System (US)
- 89bio (United States) (US)
- 89bio Inc, Rehovot, Israel
- National University of Singapore (SG)
- Corresponding author
- Loomba, Rohit
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2024-02-28
- Volume
- 73
- Issue
- 8
- Pages
- 1343-1349
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC12355936
- OpenAlex
- W4392231023
- Cited by
- 43
- References
- 32
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 9
- FWCI
- 13.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- NIDDK (P30DK120515, R01DK106419, R01DK121378, R01DK124318, U01DK061734, U01DK130190)
- Singapore Ministry of Health’s National Medical Research Council (MOH-001370)
- John C Martin Foundation (RP124)
- NHLBI (P01HL147835)
- NCATS (5UL1TR001442)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- nonalcoholic steatohepatitis, proton density fat fraction, alanine aminotransferase, aspartate aminotransferase, liver fibrosis, noninvasive fibrosis assessment
- MeSH terms
- Alanine Transaminase, Biopsy, Fatty Liver, Female, Humans, Liver, Magnetic Resonance Imaging, Male, Middle Aged, ROC Curve, Non-alcoholic Fatty Liver Disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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