Hepatobiliary System

Liver, Bile Duct - Hyperplasia

Narrative

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 1 and Figure 2 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.

Recommendations:

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

All Images

Bile duct hyperplasia in a female F344/N rat from a subchronic study.

Bile duct hyperplasia in a female F344/N rat from a subchronic study (higher magnification of Figure 1).

Authors and Reviewers

Author

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

John Cullen, VMD, PhD, DACVP, FIATP
Anatomic Pathology, Professor
North Carolina State University College of Veterinary Medicine
Raleigh, NC

David E. Malarkey DVM, PhD, DACVP, FIATP
Head, National Toxicology Program Pathology Group
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC