P5894 - Cholestasis of Undefined Etiology. Evaluation and the Role of Ileal Bile Acid Transport (iBAT) Inhibitors in Adults

Mitchell L. Shiffman, MD¹, Jennifer B. Miller, MD¹, Kimberly Taylor, RN¹, Marilou Cicero, RN², Sarah Hubbard, PA-C¹, April Ashworth, NP¹, Rebecca Rathburn, NP¹, Staci Harpster, RN¹, Karla Pray, NP², Phillip Alexander, NP²
1Bon Secours Mercy Health, Richmond, VA; 2Bon Secours Mercy Health, Newport News, VA

Introduction: Genetic cholestatic disorders (GCD) are considered a rare form of cholestatic liver disease. These disorders are due to defective bile acid (BA) section into bile, intrahepatic accumulation of toxic BA, liver injury, fibrosis, cirrhosis, and liver failure. The most well recognized forms of GCD occur in children and include Progressive Familial Intrahepatic cholestasis (PFIC) and alagille syndrome. These disorders are characterized by high serum BA levels and severe pruritus. iBAT inhibitors lower serum BA and improve/resolve pruritus in these patients (pts). Milder forms of GCD have now been recognized in adults. This has been facilitated by genetic testing for GCD which is now available for clinical use. We hypothesized that adults with cholestasis of undefined etiology with or without pruritus have a GCD.

Methods: Pts with an elevation in ALP of undefined etiology based upon serology, MRI/MRCP and/or liver histology, an elevation in serum BA and/or pruritus were screened for genetic mutations associated with cholestasis utilizing the Prevention Genetics Cholestasis panel. This test evaluates for mutations in up to 77 genes which have been associated with cholestatic disorders. Pts were excluded if they had a defined etiology for cholestasis including PBC, PSC, hepatic sarcoidosis, amyloidosis, choledocholithiasis, or a liver transplant.

Results: A total of 42 pts underwent genetic testing. The mean age of the cohort was 56 years (16-81), 26% male, 50% Caucasian, 36% African American, 12% Hispanic. The mean ALP was 281 (61-1839), GGT 278 (17-1248), AST 54 (14-275), ALT 66 (10-488), TBILI 1.2 (0.2-24.0). Mean LS by Fibroscan was 7.2 kPa (3.2-17.3) . 28/42 patients underwent liver biopsy. The most common histologic finding was a mild non-specific portal inflammation with no fibrosis. 17% had cirrhosis. 24% of pts had itching. Genetic mutations associated with cholestasis were identified in 73% of pts. A total of 24 different genes were affected in the 42 pts. 10 pts with moderate-severe pruritus and an affected gene were tread with an iBAT inhibitor. All had a reduction or complete resolution of itching.

Discussion: Mutations in genes associated with cholestasis are common in pts with cholestasis of undefined etiology. About 25% of these pts have pruritus and treatment with an iBAT inhibitor leads to improvement/resolution of itching. Testing for GCD appears to be useful in the evaluation of pts with cholestasis of undefined etiology.

Disclosures:
Mitchell Shiffman: 89 Bio – Grant/Research Support. Akero – Grant/Research Support. Altimune – Grant/Research Support. Atea – Grant/Research Support. Camarus – Grant/Research Support. Durect – Grant/Research Support. Exelixis – Advisory Committee/Board Member. FujiFilms – Speakers Bureau. Galactin – Grant/Research Support. Genentech – Grant/Research Support, Speakers Bureau. Gilead – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. HepQuant – Advisory Committee/Board Member, Grant/Research Support. Intercept – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. INtra-Sana – Consultant, Speakers Bureau. Ipsen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Madrigal – Grant/Research Support, Speakers Bureau. Mirum – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. NovoNordisk – Grant/Research Support. Viking – Grant/Research Support.
Jennifer Miller indicated no relevant financial relationships.
Kimberly Taylor indicated no relevant financial relationships.
Marilou Cicero indicated no relevant financial relationships.
Sarah Hubbard: Gilead – Speakers Bureau.
April Ashworth indicated no relevant financial relationships.
Rebecca Rathburn: GIlead – Advisory Committee/Board Member.
Staci Harpster indicated no relevant financial relationships.
Karla Pray indicated no relevant financial relationships.
Phillip Alexander indicated no relevant financial relationships.

Mitchell L. Shiffman, MD¹, Jennifer B. Miller, MD¹, Kimberly Taylor, RN¹, Marilou Cicero, RN², Sarah Hubbard, PA-C¹, April Ashworth, NP¹, Rebecca Rathburn, NP¹, Staci Harpster, RN¹, Karla Pray, NP², Phillip Alexander, NP². P5894 - Cholestasis of Undefined Etiology. Evaluation and the Role of Ileal Bile Acid Transport (iBAT) Inhibitors in Adults, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.