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.
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.
So the question, as narrowly as I can put it: whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is.
Numbers rather than impressions, if you have them.
pat_auckland 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.CardioMD 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 8 months on GLP-1 therapy:
| Marker | Baseline | Current | Normal Range |
|---|---|---|---|
| ALT | 72 | 24 | 7-56 U/L |
| AST | 50 | 26 | 10-40 U/L |
| GGT | 67 | 30 | 9-48 U/L |
| ALP | 97 | 74 | 44-147 U/L |
FibroScan also improved — liver stiffness from 10.5 kPa to 5.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.
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View Resultspat_auckland 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.
From the other side of the consultation, briefly.
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 328 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible fibrosis). Diagnosed with NAFLD.
After 14 months: CAP dropped to 241 dB/m (minimal steatosis) and stiffness normalized to 4.8999999999999995 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.