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ForumsMASH / Liver DiseaseMy fatty liver reversal — need advice

My fatty liver reversal — need advice

InsuranceTom Mon, Oct 7, 2024 at 1:57 AM 16 replies 1,906 viewsPage 1 of 4
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InsuranceTom
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Oct 7, 2024 at 1:57 AM#1

A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about liver and MASH, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

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.

The condition it depends on

ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.

The practical version

With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most threads assume.

What I am not sure about

The question I want answered is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Tell me what I have not thought of.

— InsuranceTom · corrections welcome and will be edited into this post with credit
50 20lisa_labSD, adam_van, Dr.SurgeonPGH and 47 others
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Dr.RaviCardio
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Oct 7, 2024 at 2:30 AM#2
InsuranceTom 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: Oct 7, 2024 at 3:30 AM
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SarahChen_PharmD
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Oct 7, 2024 at 3:03 AM#3
InsuranceTom 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.
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hans_munich
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Oct 7, 2024 at 3:36 AM#4
SarahChen_PharmD said:
NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.

Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 6 months on GLP-1 therapy:

MarkerBaselineCurrentNormal Range
ALT60227-56 U/L
AST582610-40 U/L
GGT65349-48 U/L
ALP1057244-147 U/L

FibroScan also improved — liver stiffness from 8.5 kPa to 5.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.

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tyler_CSCS
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Oct 7, 2024 at 6:40 AM#5
Dr.RaviCardio 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…

This is my experience too, for whatever a second data point is worth. Nothing to add that would improve it.

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