Ciliated bile duct epithelium in the liver of a Zellweger patient

Mutations in cilium proteins polycystin 1 and 2 are linked to polycystic diseases in kidney and liver. In rats bile duct cells possess a single cilium; its mechanostimulation by bile flow increases intracellular Ca++ and lowers cAMP that drives HCO3 secretion (Masyuk, 2006). In contrast human liver has no ciliated bile ducts, except for a single report (Yoshino, 1979) not confirmed by others. We report the presence of multiple cilia on intralobular bile duct cells in the liver of a 1 m old girl born to non-consanguinous W-European parents. Her head circumference was below the 3rd P for her age and she showed minor facial dysmorphia, major hypotonia, increased liver enzymes and hypoglycemia. A Zellweger syndrome was suggested by strongly increased VLCFA and cortical renal cysts. Further work-up revealed abnormal ABR with a threshold of 80db. The baby died at 3.5 m in status epilepticus. Standard microscopy of the liver was unremarkable, but immuno-localisation of catalase and AGT showed staining in the parenchymal cytoplasm instead of in granules. By electron microscopy no peroxisome-like organelles were found; macrophage lysosomes contained typical but small trilamellar inclusions, and insoluble lipid. The lumen of 9/11 interlobular bile ducts in different blocks of a surgical biopsy sample demonstrated multiple cilia in addition to normal microvilli. Cilia were incomplete, for ex. single tubuli instead of doublets. In bile ducts of 5 out of 6 other Zellweger livers we did not observe cilia. We propose that ciliated cells reflect a partial transdifferentiation likely related to specific mutations.