MASH resolution without worsening fibrosis — endpoint analysis

PharmHunterJen said:

Relative and absolute effects need reading together.

This is exactly what I could not find anywhere else. Sending this to two other people who asked me the same thing last week.

Clinical perspective, offered as context rather than as advice.

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.

jim_asheville said:

The gap between trial results and real-world results is consistent and it is not fraud.

Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 322 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 14 months: CAP dropped to 235 dB/m (minimal steatosis) and stiffness normalized to 5.8 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.

MASHdoc_SA said:

The liver data is among the strongest non-weight findings in the class.

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:

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.

Moderator note: the sourcing question belongs in the vendor section and has been split out. No action needed from anybody.