As promised, I am going to propose, what I would call a "staging" system for chronic rejection. It is based on personal experience combined with that gained from the literature. However, as we discussed at the last Banff Conference, chronic rejection is more difficult to approach than acute rejection for the following reasons:

  1. Although they most commonly occur together, chronic rejection can preferentially affect either the bile ducts or the arteries. Thus, individual cases may show severe arteriopathy, but minimal duct loss or severe duct loss with only minimal arteriopathy.
  2. There may be sampling problems associated with portal tracts counts and bile duct loss.
  3. Bile duct loss may be a reversible phenomenon.
  4. The current cutoff of 50% bile duct loss to establish the diagnosis may be too stringent to recognize early stages of the disorder.

The following are possible solutions to these problems:

  1. Descriptive adjectives can be added to define the type of chronic rejection identified(e.g. chronic "ductopenic" rejection and chronic "arteriopathic" rejection). In most instances, the diagnosis of chronic rejection made on needle biopsy specimens will be chronic (ductopenic) rejection. However, I personally have seen several cases(albeit rare) where the diagnosis of chronic arteriopathic rejection could be established on a needle biopsy. In failed allografts, most cases will likely be diagnosed as chronic (ductopenic and arteriopathic) rejection.
  2. Although not morphological, the addition of liver injury tests to the criteria for the diagnosis of chronic ductopenic rejection can minimize, but not eliminate the sampling problem. Although precise data will be available by the time of the conference. An arbitrarily chosen value of > 400 IU/L for gamma glutamyltranspeptidase, combined with the morphological data, further substantiates the diagnosis. This can added either as a strict criterion, or as a suggestion in the text.
  3. The potential reversibility of chronic rejection will have to be spelled out in the document, stressing that the decision to proceed with retransplantation should be undertaken only after a thorough clinicopathological correlation and ultimately dictated by clinical symptomology.
  4. This will be addressed in the proposed staging system.

Table 1. Histopathological Staging of chronic (ductopenic) rejection.
DIAGNOSIS HISTOPATHOLOGICAL FINDINGS
Early chronic (ductopenic) rejection Atrophic biliary epithelial changes in more than an occasional bile duct, characterized by eosinophilic transformation of the cytoplasm, uneven nuclear spacing, ducts only partially lined by epithelial cells and biliary epithelial cytological atypia. All of the portal tracts may not have bile ducts, but duct loss is seen in < 50% of the triads.
Late chronic ductopenic rejection Loss of bile ducts in >50% of the triads, associated with collagenization of the portal tracts connective tissue. Centrilobular hepatocanalicular cholestasis, perivenular sclerosis and centrilobular hepatocellular dropout may also be present.
Chronic (arteriopathic) rejection Convincing foam cell arteriopathy, that cannot otherwise be explained.

This document is intended as a starting point for discussion, and not the final consensus, which is likely to be significantly different.


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