Chronic Rejection

Chronic rejection usually does not occur within 60 days after transplantation, is frequently irreversible and is defined by two main histopathologic features: obliterative vasculopathy and loss of bile ducts $.
Chronic rejection most frequently develops after an unresolved episode or multiple episodes of acute rejection, or over a period of months to years, with few or no clinically apparent acute rejection episodes. If clinical symptoms are present, they resemble those of acute rejection, until allograft dysfunction becomes severe enough to cause jaundice. Late findings include biliary sludging or biliary strictures, hepatic infarcts, and loss of hepatic synthetic function.
Standard liver function tests usually show a progressive cholestatic pattern, with preferential increase of -glutamyl transpeptidase and alkaline phosphatase levels.
The two histopathologic findings $ that are indicative of chronic rejection are loss of small (<60 m) bile ducts involving more than 50% of the triads and obliterative arteriopathy with foam cells. Both features usually occur together, but cases with either isolated bile duct loss or foam cell arteriopathy alone may occur. Early stages of chronic rejection usually show only mild portal inflammation, with eosinophilic transformation of the cytoplasm of the biliary epithelium, intraepithelial lymphocytes, uneven spaces of the nuclei, and only partial lining of the ductular circumference by epithelium. The diagnosis in these cases is strengthened by repeated biopsies and clinical correlation.