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ForumsMASH / Liver DiseaseMASH resolution without worsening fibrosis — looking for input

MASH resolution without worsening fibrosis — looking for input

PeptideSynthNJ Wed, Jul 2, 2025 at 8:50 AM 40 replies 1,673 viewsPage 1 of 8
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PeptideSynthNJ
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Jul 2, 2025 at 8:50 AM#1

Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.

The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.

Where I think it is weakest: the comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.

The question I want answered is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Numbers rather than impressions, if you have them.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
28 23wanda_boise, NurseAsh_DET, BenResearch_OR and 25 others
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DanielChem_CHI
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Jul 2, 2025 at 10:32 AM#2
PeptideSynthNJ said:
The liver data is among the strongest non-weight findings in the class.

NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy. The Phase 2b data for semaglutide showed 59% NASH resolution (vs 17% placebo) with 43% achieving fibrosis improvement[1].

Mechanism: GLP-1R activation reduces hepatic lipogenesis, increases fatty acid oxidation, reduces hepatic inflammation, and may directly reduce hepatic stellate cell activation (fibrosis pathway).

With resmetirom (thyroid hormone receptor agonist) recently approved for NASH, the field is evolving rapidly. Combination approaches (GLP-1 + resmetirom) are being explored.

References:
[1] Newsome PN, et al. N Engl J Med. 2021;384(12):1113-1124.
27 22Dr.DermMIA, fiona_VT, denise_HTX and 24 others
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TrialNerd_Beth
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Jul 2, 2025 at 12:14 PM#3
PeptideSynthNJ said:
The liver data is among the strongest non-weight findings in the class.

Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.

Baseline: "Moderate hepatic steatosis, liver span 17.2cm, echogenic texture consistent with fat infiltration"
Month 8: "Mild steatosis, liver span 15.8cm, improved echogenicity"
Month 14: "Minimal to no steatosis, normal liver span 14.5cm, normal echotexture"

My liver literally shrank and de-fattened. The ultrasound tech said she's seen this pattern increasingly in GLP-1 patients and it's remarkable how consistently the fatty liver resolves.

26 21TomTeleRx, DoseLogDan, SleepFixSam and 23 others
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LindaRN_retired
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Jul 2, 2025 at 1:56 PM#4
TrialNerd_Beth said:
Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.

Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 313 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 11 months: CAP dropped to 236 dB/m (minimal steatosis) and stiffness normalized to 4.8999999999999995 kPa. Hepatologist says the liver is essentially healing itself as the metabolic stress resolves.

GLP-1 agonists may become first-line NASH therapy. The Phase 3 data on semaglutide for NASH is very promising.

25 20LondonLisa, mike_nyc, VendorMark and 22 others
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NurseLeah_Nash
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Jul 2, 2025 at 11:53 PM#5
DanielChem_CHI said:
NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.

Adding a me-too, because a thread of one person's experience is not much use. The detail I would add is minor and it is already implied above.

24 19Dr.NateNeph, PharmD_Rodriguez, julia.endo and 21 others
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