Obeticholic acid shows therapeutic potential in LPAC syndrome

The selective farnesoid-X receptor agonist obeticholic acid appears to improve symptoms of low phospholipid-associated cholelithiasis (LPAC) syndrome in patients who have inadequate response or intolerance to ursodeoxycholic acid, as shown in a small study.

Researchers reviewed the medical records of five patients (median age 29 years, four women) with LPAC syndrome treated with obeticholic acid. Of these patients, four were found to have the ABCB4 variant. None had hepatic fibrosis.

All patients received obeticholic acid at an initial dose of 5 mg daily and then 10 mg daily for a median period of 36 months. Treatment was administered alone in one patient or in combination with ursodeoxycholic acid in four patients. None of the patients experienced adverse effects.

Treatment with obeticholic acid led to symptom improvement in four patients, with three experiencing complete improvement and one having partial improvement. Only a single patient obtained no clinical benefit.

In one patient who achieved symptom resolution with obeticholic acid, results of blood liver tests showed abnormalities. Furthermore, three of the four patients who responded clinically to their medications showed persisting radiological signs of hepatolithiasis.

Ursodeoxycholic acid is the only drug approved for the treatment of LPAC syndrome. However, some patients do not respond to ursodeoxycholic acid and, in turn, experience symptom recurrence and complications. Experimental studies have shown that drugs that activate the farnesoid-X receptor (FXR) may be helpful for these patients. FXR is the main gene that controls the expression of ABCB4, a protein that is important for bile acid transport.

Larger studies are warranted to confirm the present data.