Semin Liver Dis
DOI: 10.1055/s-0041-1739455
Review Article

The Neglected Role of Bile Duct Epithelial Cells in NASH

Massimiliano Cadamuro
1  Department of Molecular Medicine (DMM), University of Padua, Padua, Italy
,
Alberto Lasagni
2  Division of General Medicine, Padua University-Hospital, Padua, Italy
,
Samantha Sarcognato
3  Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
,
Maria Guido
3  Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
4  Department of Medicine (DIMED), University of Padua, Padua, Italy
,
Roberto Fabris
5  Division of Clinica Medica 3, Center for the Study and the Integrated Management of Obesity, Padua University-Hospital, Padua, Italy
,
Mario Strazzabosco
6  Department of Internal Medicine, Digestive Disease Section, Liver Center, Yale University, New Haven, Connecticut
,
Alastair J. Strain
7  School of Biosciences, University of Birmingham, Birmingham, United Kingdom
,
Paolo Simioni
2  Division of General Medicine, Padua University-Hospital, Padua, Italy
4  Department of Medicine (DIMED), University of Padua, Padua, Italy
,
Erica Villa
8  Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia and Modena University-Hospital, Modena, Italy
,
Luca Fabris
1  Department of Molecular Medicine (DMM), University of Padua, Padua, Italy
2  Division of General Medicine, Padua University-Hospital, Padua, Italy
6  Department of Internal Medicine, Digestive Disease Section, Liver Center, Yale University, New Haven, Connecticut
› Author Affiliations

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and affects 25% of the population in Western countries. NAFLD is the hepatic manifestation of the metabolic syndrome, linked to insulin resistance, which is the common pathogenetic mechanism. In approximately 40% of NAFLD patients, steatosis is associated with necro-inflammation and fibrosis, resulting in nonalcoholic steatohepatitis (NASH), a severe condition that may progress to cirrhosis and liver cancer. Although the hepatocyte represents the main target of the disease, involvement of the bile ducts occurs in a subset of patients with NASH, and is characterized by ductular reaction and activation of the progenitor cell compartment, which incites portal fibrosis and disease progression. We aim to dissect the multiple biological effects that adipokines and metabolic alterations exert on cholangiocytes to derive novel information on the mechanisms driven by insulin resistance, which promote fibro-inflammation and carcinogenesis in NASH.



Publication History

Publication Date:
18 November 2021 (online)

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