A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA

Background & Aims: In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment. Methods: We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5x upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. Results: Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p>0.05). The proportion of patients with ALP = 15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p Conclusion: Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses. Lay summary: Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.Peer reviewe

Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. This syndrome is infrequent and corresponds to a peculiar small subgroup of patients with symptomatic gallstone disease. The patients with the LPAC syndrome present typically with the following main features: age less than 40 years at onset of symptoms, recurrence of biliary symptoms after cholecystectomy, intrahepatic hyperechoic foci or sludge or microlithiasis along the biliary tree. Defect in ABCB4 function causes the production of bile with low phospholipid content, increased lithogenicity and high detergent properties leading to bile duct luminal membrane injuries and resulting in cholestasis with increased serum gamma-glutamyltransferase (GGT) activity. Intrahepatic gallstones may be evidenced by ultrasonography (US), computing tomography (CT) abdominal scan or magnetic resonance cholangiopancreatography, intrahepatic hyperechogenic foci along the biliary tree may be evidenced by US, and hepatic bile composition (phospholipids) may be determined by duodenoscopy. In all cases where the ABCB4 genotyping confirms the diagnosis of LPAC syndrome in young adults, long-term curative or prophylactic therapy with ursodeoxycholic acid (UDCA) should be initiated early to prevent the occurrence or recurrence of the syndrome and its complications. Cholecystectomy is indicated in the case of symptomatic gallstones. Biliary drainage or partial hepatectomy may be indicated in the case of symptomatic intrahepatic bile duct dilatations filled with gallstones. Patients with end-stage liver disease may be candidates for liver transplantation

ASBT inhibitors in cholangiopathies – good for mice, good for men?

International audienceBile acids (BAs) retention in the liver is a potent determinant of liver failure risk inchronic cholestatic diseases. Schematically, these diseasesinclude « inherited » forms resulting from ABCB11, ATPB8, ABCB4, CFTR, JAGGED1 gene defects and acquired mmune mediated-pathologies such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)

Caractéristiques des maladies associées à la cirrhose biliaire primitive (réévaluation sur une série de 206 malades)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Ursodeoxycholic acid in chronic hepatitis C

Cytoprotective but anti‐apoptoti

Elastography in hepatology

A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis toward cirrhosis. Consequently, liver fibrosis assessment plays an important role in hepatology. Besides its importance for prognosis, determining the level of fibrosis reveals the natural history of the disease and the risk factors associated with its progression, to guide the antifibrotic action of different treatments. Currently, in clinical practice, there are three available methods for the evaluation of liver fibrosis: liver biopsy, which is still considered to be the ‘gold standard’; serological markers of fibrosis and their mathematical combination – suggested in recent years to be an alternative to liver biopsy – and, more recently, transient elastography (TE). TE is a new, simple and noninvasive method used to measure liver stiffness. This technique is based on the progressing speed of an elastic shear wave within the liver. Currently, there are only a few studies that have evaluated TE effectiveness in chronic liver diseases, mostly in patients infected with the hepatitis C virus. Further studies are needed in patients with chronic liver disease, to assess the effectiveness of the fibrosis treatment

Localization of the DCMs in the different domains of the ABCB4 protein in the complete series of patients with LPAC

<p><b>Copyright information:</b></p><p>Taken from "Low phospholipid associated cholelithiasis: association with mutation in the /gene"</p><p>http://www.OJRD.com/content/2/1/29</p><p>Orphanet Journal of Rare Diseases 2007;2():29-29.</p><p>Published online 11 Jun 2007</p><p>PMCID:PMC1910597.</p><p></p