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ForumsMASH / Liver DiseaseLiver enzymes normal for the first time in a decade — looking for input

Liver enzymes normal for the first time in a decade — looking for input

DataDave Wed, Sep 10, 2025 at 2:47 AM 32 replies 1,580 viewsPage 1 of 7
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DataDave
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Sep 10, 2025 at 2:47 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 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 would genuinely help is knowing whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. I would rather have one careful answer than five confident ones.

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.
42 12VendorMark, COA_Karl, MikeFit_NJ and 39 others
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CarlaRPh_TPA
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Sep 10, 2025 at 3:20 AM#2
DataDave 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.
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mike.trainer_LA
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Sep 10, 2025 at 3:53 AM#3
DataDave 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 338 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 12 months: CAP dropped to 241 dB/m (minimal steatosis) and stiffness normalized to 5.9 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.

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TrialTracker_MD
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Sep 10, 2025 at 4:26 AM#4
mike.trainer_LA said:
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 338 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible…

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.

39 9Dr.PulmRoch, maya_sedona, stefan_berlin and 36 others
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matt_MKE
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Sep 10, 2025 at 7:27 AM#5
CarlaRPh_TPA 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…

Same experience, arrived at from the opposite direction.

Last edited: Sep 10, 2025 at 10:27 AM
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