
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:
- 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.
- There may be sampling problems associated with portal tracts
counts and bile duct loss.
- Bile duct loss may be a reversible phenomenon.
- 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:
- 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.
- 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.
- 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.
- 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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TPIS
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