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ForumsMASH / Liver DiseaseEfinopegdutide MASH data — July 2024

Efinopegdutide MASH data — July 2024

KarenAZ_mom Thu, May 30, 2024 at 2:14 PM 39 replies 2,830 viewsPage 1 of 8
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KarenAZ_mom
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Aug 2024
Scottsdale, AZ
May 30, 2024 at 2:14 PM#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.

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 after is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is.

Numbers rather than impressions, if you have them.

38 8anna.melb_AU, mark_tokyo, hans_munich and 35 others
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Dr.RaviCardio
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May 30, 2024 at 2:50 PM#2
KarenAZ_mom 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 316 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 14 months: CAP dropped to 229 dB/m (minimal steatosis) and stiffness normalized to 5.2 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.

37 7anna.melb_AU, mark_tokyo, hans_munich and 34 others
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tyler_CSCS
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Phoenix, AZ
May 30, 2024 at 3:26 PM#3
Dr.RaviCardio said:
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 316 dB/m (moderate steatosis) and stiffness 9.8 kPa (possible…

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.

36 6Dr.SportsMedIN, amy_econ_NJ, bbq_ray_KC and 33 others
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sean_dublin
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Dublin, IE
May 30, 2024 at 4:02 PM#4
KarenAZ_mom 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. Posting only so the count is not one.

35 5NurseLeah_Nash, gary_naperville, sean_dublin and 32 others
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ingrid_STO
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Jul 2024
Stockholm, SE
May 30, 2024 at 7:24 PM#5

From the other side of the consultation, briefly.

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.
34 4WendyG_ATL, SaraMom3, Dr.MetabolicMD and 31 others
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