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Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test.
- Source :
-
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2024 Oct 01; Vol. 30 (10), pp. 982-990. Date of Electronic Publication: 2024 Jun 12. - Publication Year :
- 2024
-
Abstract
- New methods for measuring hepatic improvement in clinical trials and the clinic are needed. One new method, HepQuant SHUNT, detected dose-dependent improvements in hepatic function and portal physiology in the phase 1b study (NCT03842761) of avenciguat, an activator of soluble guanylyl cyclase that is being developed for the treatment of portal hypertension. Herein, we examined whether HepQuant Duo, an easy-to-administer test version, could similarly detect the effects of avenciguat. Twenty-three patients with Child-Pugh A cirrhosis and liver stiffness >15 kPa received either a placebo (n = 5) or a maximum twice-daily avenciguat dose of 1, 2, or 3 mg (n = 6 per group) for 28 days. The DuO test was performed at baseline and on days 11 and 27 in each subject. The test involved administering 40 mg of d4-cholate orally, measuring d4-cholate concentrations in serum at 20 and 60 minutes, and calculating portal hepatic filtration rate, disease severity index, portal-systemic shunting (SHUNT%), and hepatic reserve (HR%). Avenciguat demonstrated dose-dependent improvement in all test parameters. Changes from baseline in SHUNT% after 27 days' treatment were 0.1 ± 9.0% for placebo, 1.7 ± 5.5% for 1 mg twice-daily, -3.2 ± 2.7% for 2 mg twice-daily, and -6.1 ± 5.0% for 3 mg twice-daily (paired t test for change from baseline p = 0.98, 0.48, 0.04, and 0.03, respectively). The changes detected by HepQuant DuO were similar to those previously observed and reported for HepQuant SHUNT. The results support further study of avenciguat in treating portal hypertension and spotlight the utility of HepQuant DuO in the development of drug therapy for liver disease. HepQuant DuO facilitates the use of function testing to measure hepatic improvement in clinical trials and the clinic.<br /> (Copyright © 2024 American Association for the Study of Liver Diseases.)
- Subjects :
- Humans
Male
Female
Middle Aged
Treatment Outcome
Aged
Severity of Illness Index
Administration, Oral
Double-Blind Method
Liver Function Tests statistics & numerical data
Liver Function Tests methods
Adult
Soluble Guanylyl Cyclase metabolism
Dose-Response Relationship, Drug
Time Factors
Liver Cirrhosis drug therapy
Liver Cirrhosis complications
Liver Cirrhosis diagnosis
Liver Cirrhosis blood
Hypertension, Portal drug therapy
Hypertension, Portal etiology
Hypertension, Portal diagnosis
Liver drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1527-6473
- Volume :
- 30
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Publication Type :
- Academic Journal
- Accession number :
- 38869987
- Full Text :
- https://doi.org/10.1097/LVT.0000000000000420