Cholangiocyte death in ductopenic cholestatic cholangiopathies: Mechanistic basis and emerging therapeutic strategies

SIMONI-NIEVES A.; GÓMEZ-QUIROZ L.E.; SALAS SILVA E.S.; BUCIO L.; ROMA M.G.; LÓPEZ-RAMIREZ J.; GUTIÉRREZ-RUIZ M.C.

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2019 vol. 218 p. 324 - 339

0024-3205

Among hepatic diseases, cholestatic ductopeniccholangiopathies are poorly studied, and they are rarely given the importancethey deserve, especially considering their high incidence in clinical practice.Although cholestatic ductopenic cholangiopathies have different etiologies andpathogenesis, all have the same target (the cholangiocyte) and similarmechanistic basis of cell death. Cholestatic cholangiopathies are characterized,predominantly, by obstructive or functional damage in the biliary epithelium,resulting in an imbalance between proliferation and cholangiocellular death, thusleading to the progressive disappearance of bile ducts, as has been shown tooccur in primary sclerosing cholangitis, primary biliary cholangitis, low-phospholipid-associatedcholelithiasis syndrome, cystic fibrosis-related liver disease, anddrug-induced ductopenia, among other biliary disorders. This review summarizesthe features of the more common ductopenic syndromes and the cellularmechanisms involved in cholengiocellular death, with focus on the main forms ofcholangiocyte death described so far, namely apoptosis, autophagy, necrosis andnecroptosis. It also emphasizes the importance to study in depth themolecular mechanisms of cholengiocyte death to make possible to counteract them with therapeutic purposes.These therapeutic strategies are limited in number and efficacy at present, andthis is why it is important to find complementary, safe strategies to stimulatecholangiocellular proliferation in order favor bile duct replenishment as well.Successful in finding appropriate treatments would prevent the patient fromhaving liver transplantation as the only therapeutic alternative.