PAC (France)

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. To study the efficacy of obeticholic acid (OCA) in patients with LPAC syndrome with an inadequate response or intolerance to UDCA. This was a retrospective study of patients with LPAC syndrome treated with OCA, a selective FXR agonist. 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. 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.

The aldosterone-to-renin ratio (ARR) is commonly used in the screening of primary aldosteronism. However, limited information is available with regard to the intra-patient variability in this ratio. Our objective is to determine whether ARR measurements are reliably consistent over both the short- and long-term. We assessed the short-term variability of the aldosterone-to-renin ratio in 116 unmedicated, essential hypertensive participants who had two blood samples taken in the morning of the same day for measurement of aldosterone and active plasma renin concentration. Long-term variability was studied in 22 unmedicated, essential hypertensive participants who had two blood samples taken approximately 1 year apart. All samples were taken under highly standardized conditions. Our data show that renin, aldosterone and the aldosterone-to-renin ratio show marked variations, both when measured on the same day and when assessed at a longer interval. The ARR becomes increasingly variable as its mean value increases. Its degree of variability is similar in both the short-term and the long-term. Based on our findings, we conclude that the aldosterone-to-renin has acceptable short-term variability in the lower ranges, but increasingly dubious reliability as aldosterone-to-renin values rise. Thus, in a clinical context, great caution should be taken in interpreting point-measurements of moderate to high aldosterone-to-renin ratio values.

International audience

This paper is summarized from a report prepared by the Houston Regional Monitoring Corporation for submission to the U.S. Environmental Protection Agency explaining the methodology used in the East Harris County and West Chambers County for assessing community exposure to volatile compounds. The paper briefly discusses the program description, the rationale for selecting candidate airborne chemicals for detailed health effects assessments, and the method used to develop consensus guidance values based on accepted risk assessment methodologies. The results of a 6-month monitoring period are presented with health assessment indicators.