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.
What I am trying to establish is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is.
Practical detail welcome, however dull — the duller the better.
PharmacoVig_BOS 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.
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.
[1] Newsome PN, et al. N Engl J Med. 2021;384(12):1113-1124.
Dr.KarenChen said:NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.
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.
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Shop Reference StandardsPharmacoVig_BOS 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.
Mine went the same way, slower. Nothing to add that would improve it.
From the other side of the consultation, briefly.
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.
[1] Sanyal AJ, et al. N Engl J Med. 2024.