64 Arch Pathol Lab Med—Vol 128, January 2004 Pathology of Portal Vein in Allograft Rejection—Jain et al Total Fibrous Obliteration of Main PortalVein and Portal Foam Cell Venopathy in Chronic Hepatic Allograft Rejection Dhanpat Jain, MD; Marie E. Robert, MD; Victor Navarro, MD; Amy L. Friedman, MD; James M. Crawford, MD, PhD ● Context.—Chronic hepatic allograft rejection is charac- terized by arteriopathy and bile duct loss. Pathology of the portal vein or its branches is not considered to play a major role in chronic rejection. Objective.—A recent case of chronic rejection with total fibrous obliteration of the portal vein at the hilum and graft loss prompted us to retrospectively analyze cases of failed allografts for portal vein changes. Design.—Six cases of failed hepatic allograft recorded in our files from 1994 to 1998 were selected for the study. For comparison, 4 cases of hepatitis C cirrhosis were in- cluded. Clinical features, including arteriograms or Dopp- ler studies, were reviewed whenever available. Sections taken from the hilum and random parenchyma stained with routine hematoxylin-eosin, elastic van Gieson, and Masson trichrome were examined by 3 experienced liver pathologists in a randomized, blinded fashion. Results.—Significant hepatic artery occlusion with foam cell change and bile duct loss was seen in all cases of chronic rejection (3/3), but not in the other cases. Foam cell change in the portal vein at the hilum (3/3) and oc- casionally into the distal branches (2/3) with variable oc- clusion of the lumen was seen only in cases of chronic hepatic allograft rejection. Mild luminal narrowing was ob- served in all the cases of cirrhosis (4/4) as a result of phle- bosclerosis, most likely representing a change secondary to portal hypertension. Total obliteration of the portal vein at the hilum was seen in the index case (case 1) only. Conclusion.—Portal venopathy can be a significant find- ing in chronic hepatic allograft rejection and may contrib- ute to graft dysfunction or failure.Two-vessel disease must be considered in cases of chronic hepatic allograft rejec- tion, and pathologists should thoroughly examine the hi- lum in explanted hepatic allografts. (Arch Pathol Lab Med. 2004;128:64–67) C hronic hepatic allograft rejection is defined as an ir- reversible form of injury characterized by bile duct loss and/or obliterative vasculopathy. 1–4 With better graft survival largely due to improved surgical techniques, bet- ter immunosuppression, and early treatment of infections, the incidence of chronic rejection has been decreasing. The principal form of obliterative vasculopathy seen in chronic rejection is foam cell arteriopathy and usually involves the large and medium-sized arteries close to the hilum. Sim- ilar changes in the portal vein (PV) or its branches as a feature of chronic rejection have been described only rare- ly and are not considered graft threatening. 5,6 We recently encountered a case of chronic rejection in which total oblit- eration of the PV at the hilum was the most impressive pathologic finding. This observation led us to examine all resected specimens of graft loss seen at our institution and to evaluate changes in the PV and its radicals. Accepted for publication August 8, 2003. From the Departments of Pathology (Drs Jain and Robert), Medicine (Dr Navarro), and Liver Transplant Unit (Dr Friedman), Yale University School of Medicine, New Haven, Conn; and the Department of Pa- thology, University of Florida College of Medicine, Gainesville (Dr Crawford). Reprints: Dhanpat Jain, MD, Department of Pathology,Yale Univer- sity School of Medicine, PO Box 208023, New Haven, CT 06520-8023 (e-mail: dhanpat.jain@yale.edu). MATERIALS AND METHODS All cases of failed hepatic allografts were identified from the files of the Liver Transplant Unit at Yale New Haven Hospital (New Haven, Conn). Only those cases in which the explants were available for histologic examination were included in the study. The cases were classified as chronic rejection based on established criteria. 7 All the other explants were put in the non–chronic he- patic allograft rejection category. Two hilar sections and 2 ran- dom sections from the parenchyma stained with hematoxylin- eosin, elastic van Gieson, and Masson trichrome stains were re- viewed independently by 3 pathologists in a randomized, blinded fashion. All portal tracts, including those at the hilum, were ex- amined for histologic evaluation of the hepatic artery (HA), PV, and bile ducts. Percent occlusion in the HA or PV in the hilar and septal vessels and percent bile duct loss in the portal tracts were graded on a quartile scale (1, 0%–25%; 2, 26%–50%; 3, 51%– 75%, and 4, 76%–100%). Foam cell change, intimal fibroplasia, and inflammation were also recorded and graded as mild, mod- erate, or severe. The mean parameter scores of the 3 observers were used to calculate the mean  SD for each explant group. The vascular changes in the chronic rejection group are thought to be related to chronic rejection; therefore, 2 groups that do not have any components of chronic rejection were selected for com- parison, namely, (1) cases of acute allograft failure for which ex- plants were available and (2) cases of non–allograft-related chron- ic inflammatory liver disorder with portal hypertension, which are subjected to the same rapid specimen processing in the sur- gical pathology suite and rigorous morphologic evaluation as are failed hepatic allografts. The second category consisted of 4 pri- mary explants for hepatitis C cirrhosis. Clinical features, includ-