MASH and MASLD

The disease, and what it is now called

The condition is fat accumulation in the liver accompanied by inflammation, occurring in the context of metabolic dysfunction rather than alcohol intake. It sits at the more advanced end of a spectrum that begins with fat accumulation alone. The naming changed recently, and both sets of terms remain in circulation, which matters when searching literature or writing a protocol.

The regulatory position changed in March 2024, when the Food and Drug Administration approved resmetirom, a new molecular entity, in this indication.^[S3] The approval followed a phase 3 trial published the same year.^[S4] That is recorded here as a fact about the regulatory landscape, because it changes what a development programme in this area is measured against. This site does not discuss the efficacy of approved products or compare treatments, and nothing here is medical advice.

What a nonclinical program in this area has to settle

The difficulty in this indication is that the human disease develops over years against a background of metabolic disease, while a model has to produce the lesion in weeks. That gap shapes every design decision. A model that produces fat accumulation is not a model of steatohepatitis, and a model with inflammation is not necessarily a model with established fibrosis. Since the stage of disease a candidate is intended to act on determines which of those is required, the model choice follows from the mechanism rather than from the disease name.

One widely used approach combines low-dose streptozotocin given to neonatal male mice with a high-fat diet, which the original report describes as producing liver steatosis with diabetes one week after the diet begins.^[S5] Models of this kind have been used in programmes that reached clinical trials; two such trials are registered publicly.^[S6] This article names no supplier for any model, and the presence of a model in a clinical-stage programme says nothing about whether that programme succeeded.

References

1. Rinella ME, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 (PMID 37363821)。https://pubmed.ncbi.nlm.nih.gov/37363821/ (accessed 2026-09-03)
2. NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) — Nonalcoholic Fatty Liver Disease (NAFLD) & NASH. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash (accessed 2026-09-03)
3. Drugs@FDA — REZDIFFRA (resmetirom), NDA 217785. https://www.accessdata.fda.gov/scripts/cder/daf/ (accessed 2026-09-03)
4. Harrison SA, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390:497-509 (PMID 38324483). https://pubmed.ncbi.nlm.nih.gov/38324483/ (accessed 2026-09-03)
5. Fujii M, et al. A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. Med Mol Morphol. 2013. https://pubmed.ncbi.nlm.nih.gov/23430399/ (accessed 2026-09-03)
6. ClinicalTrials.gov — NCT04697810 (Phase 2, initiated in December 2021) and NCT02462967 (Phase 2). https://clinicaltrials.gov/study/NCT04697810 (accessed 2026-09-03)
7. 21 CFR Part 58 — Good Laboratory Practice for Nonclinical Laboratory Studies (§58.1 scope). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-58 (accessed 2026-09-03)