Ductular reactions in human liver: Diversity at the interface


  • Annette S. H. Gouw,

    1. Department of Pathology and Medical Biology, Pathology Section, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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  • Andrew D. Clouston,

    1. Centre for Liver Disease Research, School of Medicine, University of Queensland, Brisbane, Australia
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  • Neil D. Theise

    Corresponding author
    1. Departments of Pathology and of Medicine, Division of Digestive Diseases, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, NY
    • Division of Digestive Diseases, Baird Hall 17-61, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003
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    • fax: 212-420-4373

  • Potential conflict of interest: Nothing to report.

  • This work was supported in part by grants from the National Health and Medical Research Council of Australia and Royal Brisbane Hospital Foundation (to A.D.C.).


Interest in hepatic ductular reactions (DRs) has risen in recent years because of a greater appreciation of their potential roles in regeneration, fibrogenesis, and carcinogenesis. However, confusion exists because there is significant, but often unappreciated diversity at the tissue, cellular, and subcellular levels in DRs of different diseases and stages of disease. DRs are encountered in virtually all liver disorders in which there is organ-wide liver damage and cell loss, but are also present in focal lesions such as focal nodular hyperplasia and adenoma. Moreover, diverse DR phenotypes can be present within any single disease entity, and are shaped by the etiology and evolution of the disease. Although much remains to be clarified, recent studies suggest that the diversity of appearances of the DRs are likely to reflect the differing signals at the anatomic, cellular, and molecular levels driving the proliferative response. These appear to determine the relative proportions of transit-amplifying cells, the degree of hepatocytic or cholangiocytic differentiation, and their relationships with stromal, vascular, and inflammatory components. The molecular signaling pathways governing these regenerative fate decisions closely replicate those found in human and other vertebrate embryos and more generally in stem cell niches throughout the body. Like the latter, complex interactions with matrix as well as mesenchymal and inflammatory cells, vessels, and innervation are likely to be of fundamental importance. Embracing systems/tissue biological approaches to exploring DRs, in addition to more traditional cellular and molecular biological techniques, will further enhance our understanding and, thereby, we believe potentiate new therapeutic possibilities. (HEPATOLOGY 2011)