Liver Pathology in Adult Patients with Multidrug Resistance 3 Protein Deficiency (ABCB4 Gene Mutations): Some Patients Have Small Duct Sclerosing Cholangitis
D Wendum, O Rosmorduc, V Barbu, L Arrive, J-F Flejou, R Poupon. APHP, Hopital St Antoine, Paris, France; APHP, Hopital StAntoine, Paris, France; APHP, Hôpital St Antoine, Paris, France
Background: The multidrug-resistant P-glycoprotein 3(MDR3) encoded by the ABCB4 gene acts as a phospholipid flippase. ABCB4 gene mutations result in a spectrum of cholestatic liver diseases including progressive familial intrahepatic cholestasis type 3 (PFIC-3), low phospholipid associated cholelithiasis (LPAC) and intrahepatic cholestasis of pregnancy (ICP) or unexplained anicteric cholestasis. The aim of this study was to describe the pathological features associated with ABCB4 gene mutations in adult patients.
Design: All adult patients of our institution with an ABCB4 gene mutation who have had a liver sample with pathological analysis were included. Patients with other causes of liver disease (heavy alcohol intake, viral hepatitis) were excluded. The pathological features were analyzed without knowledge of the clinical phenotype or the type of gene mutation.
Results: 12 patients (13 liver samples) were included . Six patients had a typical LPAC syndrome : 3 had normal liver histology and 3 patients had a mild ductular reaction without fibrous septa. In one case there was ductopenia. Three patients had hepatolithiasis without sclerosing cholangitis on magnetic resonance cholangiography . On liver samples these patients had a ductular reaction with or without few septa . In 2 cases there were fibro-obliterative lesions of the interlobular bile ducts. Two patients had a biliary cirrhosis, one developed an hepatocellular carcinoma. One patient had unexplained cholestasis and liver cytolysis with, on the liver biopsy, a fibro-obliterative lesion of some interlobular bile ducts and mild ductular reaction without fibrous septa. Magnetic resonance cholangiography was normal. The patient with LPAC and ductopenia had a homozygous ABCB4 gene mutation. The patient with hepatolithiasis and small duct sclerosing cholangitis and the patient with unexplained cholestasis and small duct cholangitis had a compound heterozygous ABCB4 gene mutation All the other patients had a heterozygous ABCB4 mutation.
Conclusions: In this study we show that some adult patients with ABCB4 gene mutation have small duct sclerosing cholangitis. These lesions did not seem to be associated with a severe fibrosis. There could be an association between compound heterozygous ABCB4 mutations and small duct sclerosing cholangitis.
Category: Liver & Pancreas
Monday, March 22, 2010 1:00 PM
Poster Session II # 189, Monday Afternoon