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Fibrosing Cholestatic Hepatitis C After Hematopoietic Cell Transplantation: Report of 3 Fatal Cases

Evans, Ashley T. MD*; Loeb, Keith R. MD, PhD†,‡; Shulman, Howard M. MD†,‡; Hassan, Sajida PhD; Qiu, Wan Chong BS§; Hockenbery, David M. MD*,‡; Ioannou, George N. BMBCh, MS*,∥; Chauncey, Thomas R. MD*,∥; Gretch, David R. MD, PhD§; McDonald, George B. MD*,‡

The American Journal of Surgical Pathology: February 2015 - Volume 39 - Issue 2 - p 212–220
doi: 10.1097/PAS.0000000000000345
Original Articles

Development of liver disease after hematopoietic cell transplantation is common and the causes diverse. Infection by hepatitis C virus (HCV) can be seen in patients who are chronically infected before transplant or from passage of virus from an infected donor; the normal 10-year course of hepatitis C after transplant is one of waxing and waning of serum aminotransferase enzymes, with little morbidity. In the series of 3 patients reported here, the course of hepatitis C was rapidly fatal, with the onset of jaundice at day 60 to 80 after transplant and liver histology typical of fibrosing cholestatic hepatitis (marked bile ductular proliferation, ballooned hepatocytes, and associated collagenous fibrosis centered around ductules). The bile ductular reaction pattern varied from elongated structures without a recognizable lumen to a pattern of cuboidal cells with a clear lumen. There was significant cholestasis with bile within hepatocytes and canalicular bile plugs. In situ HCV RNA hybridization studies from 1 patient showed a robust infection with high levels of HCV-infected hepatocytes and active viral replication. All 3 patients were on immunosuppressive drugs after transplant, including mycophenolate mofetil (MMF), which irreversibly inhibits inosine monophosphate dehydrogenase, on which T and B lymphocytes are dependent. We speculate that fatal fibrosing cholestatic hepatitis C in these cases was related to the immunosuppressive effects of MMF, as we had not recognized this presentation of HCV infection before the introduction of MMF.

Departments of *Medicine


§Laboratory Medicine, University of Washington School of Medicine

Clinical Research Division, Fred Hutchinson Cancer Research Center

VA Puget Sound Health Care System, Seattle, WA

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: George B. McDonald, MD, Gastroenterology/Hepatology Section (D5-114), Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024 (e-mail:

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