Obeticholic acid as a second-line treatment for low phospholipid-associated cholelithiasis syndrome.

Background: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a rare genetic cause of hepatolithiasis. A pathogenic variant of the ABCB4 gene is reported in half of all patients. Ursodeoxycholic acid (UDCA) is the only drug approved. However, in some patients, UDCA fails to prevent recurrence of symptoms and complications. Experimental evidence suggests that agonists of the farnesoid-X receptor (FXR), the main transcription factor regulating ABCB4, may be beneficial in this context.

Aim: To study the efficacy of obeticholic acid (OCA) in patients with LPAC syndrome with an inadequate response or intolerance to UDCA.

Methods: This was a retrospective study of patients with LPAC syndrome treated with OCA, a selective FXR agonist.

Results: We reviewed the records of five OCA-treated patients (4 women; median age 29; ABCB4 variant in 4; no hepatic fibrosis). All patients received OCA at an initial dose of 5 mg daily and then 10 mg daily for a median period of 36 months in combination with UDCA (4 patients) or as a monotherapy (one patient). There were no adverse effects reported. Four patients had improvement in their symptoms - three completely and one partially. One patient had no clinical benefit. Abnormalities of blood liver tests persisted in one patient despite resolution of symptoms. Radiological signs of hepatolithiasis persisted in three of the four patients who responded clinically to OCA.

Conclusions: These preliminary observations suggest that OCA may have the potential to effectively treat LPAC syndrome in patients with inadequate response or intolerance to UDCA. Larger studies are needed to confirm these data.