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  • Liver, Bile Duct - Hyperplasia

    Image of hyperplasia in the liver bile duct from a female F344/N rat in a subchronic study
    Bile duct hyperplasia in a female F344/N rat from a subchronic study.
    Figure 1 of 2
    Image of hyperplasia in the liver bile duct from a female F344/N rat in a subchronic study
    Bile duct hyperplasia in a female F344/N rat from a subchronic study (higher magnification of Figure 1).
    Figure 2 of 2
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    comment:

    Bile duct hyperplasia is not commonly seen in prechronic studies but is a common aging lesion. In chronic studies, the occasional occurrence of bile duct hyperplasia in the absence of any differences in incidence or severity among study groups likely represents a background lesion. It is more commonly seen in rats than in mice. Only some portal areas may be affected. Biliary hyperplasia may be associated with peribiliary fibrosis. When accompanied by inflammatory cells and/or oval cell proliferation, bile duct hyperplasia may be the consequence of a toxic insult. Figure 1image opens in a pop-up window and Figure 2image opens in a pop-up window show a single focal area of hyperplasia; similar lesions were not present in the other liver sections examined from this rat. This degree of bile duct hyperplasia is not commonly present in control rats in 90-day studies.

    recommendation:

    Bile duct hyperplasia should be diagnosed and assigned a severity grade whenever present as a treatment-associated change or when excessive, as in this example. Since bile duct hyperplasia is a common age-related change, the decision to diagnose it will depend upon the age of the animal. Associated lesions, such as inflammation, fibrosis, or bile duct dilation, should be diagnosed separately if warranted by the severity of these lesions

    references:

    Eustis SL, Boorman GA, Harada T, Popp JA. 1990. Liver. In: Pathology of the Fischer Rat (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 71-94.

    Evans JG, Lake BG. 1998. The digestive system II. Hepatobiliary system. In: Target Organ Pathology (Turton J, Hooson J, eds). Taylor and Francis, London, 61-98.

    Greaves P. 2007. Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Elsevier, Amsterdam.
    Abstract: http://www.sciencedirect.com/science/book/9780444527714

    Harada T, Enomoto A, Boorman GA, Maronpot RR. 1999. Liver and gallbladder. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 119-183.
    Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

    Hardisty JF, Brix AE. 2005. Comparative hepatic toxicity: Prechronic/chronic liver toxicity in rodents. Toxicol Pathol 33:35-40.
    Full Text: http://tpx.sagepub.com/content/33/1/35.full.pdf

    Haschek WM, Rousseaux CG, Wallig MA. 2010. Fundamentals of Toxicologic Pathology, 2nd ed. Academic Press, San Diego, 197-235.

    Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, Malarkey D, Kaufmann W, Kutter K, Deschl U, Nakae D, Gregson R, Winlove M, Brix A, Singl B, Belpoggi F, Ward JM. 2010. Hepatobiliary lesion nomenclature and diagnostic criteria for lesions in rats and mice (INHAND). Toxicol Pathol 38:5S-81S.
    Full Text: http://tpx.sagepub.com/content/38/7_suppl/5S.full