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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

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using 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 population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.

What I actually want to know 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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Dr.ObesityMed
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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.

Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 319 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 11 months: CAP dropped to 232 dB/m (minimal steatosis) and stiffness normalized to 5.5 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.

27 22PharmacoVig_BOS, SurmountFan_IN, PeptideChemSF and 24 others
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BethLabQueen
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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.

ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase 3 ATTAIN trial. NASH resolution was achieved in ~60% of patients[1].

This is relevant to liver and MASH because survodutide's glucagon agonism specifically targets hepatic lipid metabolism — making it potentially the best-in-class agent for NASH/MAFLD comorbid with obesity.

References:
[1] Sanyal AJ, et al. N Engl J Med. 2024.
Last edited: Jul 2, 2025 at 1:14 PM
26 21lori_vegas, Dr.PulmRoch, maya_sedona and 23 others
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julia.endo
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Jul 2, 2025 at 1:56 PM#4
BethLabQueen said:
ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase…

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.
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nick_newbie
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Jul 2, 2025 at 11:53 PM#5
Dr.ObesityMed said:
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 319 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible…

Second this.

24 19wanda_boise, NurseAsh_DET, BenResearch_OR and 21 others
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