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Evidence-based GLP-1 & peptide discussion since 2023
ForumsMASH / Liver DiseaseHas anyone dealt with mash resolution without worsening fibrosis?

Has anyone dealt with mash resolution without worsening fibrosis?

KevinCompounds Thu, Oct 31, 2024 at 11:40 AM 45 replies 2,606 viewsPage 1 of 9
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KevinCompounds
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Oct 31, 2024 at 11:40 AM#1

ALT was mildly raised at baseline, normalised at month five, and I now have no idea whether anything happened to the fibrosis that actually matters.

The question I want answered is 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.

48 18jennifer_SEA, tyler_CSCS, VanRx_Mike and 45 others
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PharmacoVig_BOS
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Oct 31, 2024 at 12:16 PM#2
KevinCompounds said:
ALT was mildly raised at baseline, normalised at month five, and I now have no idea whether anything happened to the fibrosis that actually matters.

Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 332 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 12 months: CAP dropped to 235 dB/m (minimal steatosis) and stiffness normalized to 5.3 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.

Last edited: Oct 31, 2024 at 3:16 PM
47 17Dr.GutHealth, amsterdam_pete, LondonLisa and 44 others
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MASHdoc_SA
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Oct 31, 2024 at 12:52 PM#3
PharmacoVig_BOS said:
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 332 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible…

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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hans_munich
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Oct 31, 2024 at 1:28 PM#4
KevinCompounds said:
ALT was mildly raised at baseline, normalised at month five, and I now have no idea whether anything happened to the fibrosis that actually matters.

Second this. The detail I would add is minor and it is already implied above.

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TrialNerd_Beth
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Oct 31, 2024 at 4:50 PM#5

Adding the clinical framing, because it changes how the question reads.

Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 9 months on GLP-1 therapy:

MarkerBaselineCurrentNormal Range
ALT55277-56 U/L
AST632710-40 U/L
GGT80319-48 U/L
ALP1107244-147 U/L

FibroScan also improved — liver stiffness from 8.5 kPa to 6.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.

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