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acute liver allograft rejection

Tuesday 3 May 2005

ALAR, acute hepatic allograft rejection

Images

- endothelialitis

Types

- portal acute rejection
- lobular acute rejection (15659143)
- centrilobular acute rejection

Major morphologic features

The following triad of histologic changes may be seen to variable degrees, depending on the severity of the rejection:

- 1. Mixed portal inflammatory infiltrates

  • a. Activated lymphocytes (immunocytes, immunoblasts), eosinophils, occasional plasma cells, histiocytes, and neutrophils are present and are usually confined to the portal tracts (except in severe cases, where periportal spillover may occur).

- 2. Venous endothelial inflammation (endothelialitis)

  • a. Lymphocytes and immunocytes attach to the endothelium of portal and terminal hepatic venules, involving part or all of the intravascular luminal lining.
  • b. Subendothelial infiltration of these mononuclear cells is often seen. In severe rejection, the inflammatory cells also involve the perivenular sinusoids and may be associated with perivenular ischemic necrosis of hepatocytes.
  • c. Arterioles may be involved in severe cases.

- 3. Nonsuppurative cholangitis, destructive or nondestructive

  • a. Interlobular bile ducts are surrounded and invaded by lymphocytes, immunocytes and neutrophils, with the biliary epithelium showing variable cytoplasmic vacuolization and nuclear pyknosis, dependent on the rejection severity.

Minor morphologic features

- 1. Cholestasis, mild mononuclear inflammatory infiltrates, and rare apoptosis may be present within the lobules.
- 2. When perivenular necrosis and lobular collapse are present in severe cases, sinusoidal congestion with acute hemorrhage may occur. In addition, red blood cells may be seen infiltrating into the hepatic cords (red blood cell extravasation).
- 3. In some cases perivenular inflammation with endothelialitis may occur in the absence of corresponding portal tract changes of rejection.

Note: The above histologic changes are characteristic findings of acute rejection in the early post-transplant setting (weeks to months); however, acute rejection in allografts over one year post-transplant may in fact show only mild nonspecific changes, such as mild portal and lobular inflammation, and may histologically resemble a chronic hepatitis-like reaction. In these instances, other causes such as disease recurrence, drug-induced injury, and superinfection must be ruled out before a diagnosis of possible rejection can be made; unfortunately, in some instances this exclusion process may not confidently be possible.

Banff grading system of acute allograft rejection

From Demetris AJ, Batts KP, Dhillon AP, et al: Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 1997;25:658-663.

Liver allograft pathology for acute cellular rejection is graded by use of the Banff scoring system, and is subdivided into the global assessment of mild to severe rejection, followed by a numerical score (rejection activity index, RAI).

This RAI score grades individually the degree of portal inflammation, duct damage, and endothelial inflammation, each on a scale of 0 through 3, with a total score ranging from 0 (no rejection) to 9 (severe rejection).

For example, a biopsy showing portal rejection infiltrates involving only a minority of portal tracts, with the portal infiltrate mostly lymphocytic (score = 1), bile duct damage involving a minority of ducts (score = 1), and endothelial damage involving only some portal venules (score = 1), would be graded as mild (RAI = 3 of 9).

GLOBAL ASSESSMENT

- Indeterminate (borderline, insufficient for a diagnosis of acute rejection)

  • Portal inflammatory infiltrates that fail to meet the criteria for the diagnosis of acute rejection.

- Mild

  • Rejection infiltrates in a minority of the triads that are mild and confined to the portal spaces.

- Moderate

  • Rejection infiltrates expanding most or all of the portal tracts.

- Severe

  • As above, with spillover of inflammatory cells into the periportal areas, with moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular liver cell necrosis.

REJECTION ACTIVITY INDEX (RAI)

PORTAL INFLAMMATION

- 1. Mostly lymphocytic inflammation involving but not expanding a minority of the portal triads.
- 2. Expansion of most or all of the portal tracts by a mixed inflammatory infiltrate containing lymphocytes with occasional blasts, neutrophils, and eosinophils.
- 3. Marked expansion of most or all of the portal tracts by a mixed infiltrate containing numerous immunoblasts and eosinophils, with spillover of the cells into the periportal region.

BILE DUCT INFLAMMATION/DAMAGE

- 1. A minority of the ducts are surrounded and infiltrated by inflammatory cells and show only mild reactive changes (e.g., increased nuclear/cytoplasmic ratio).
- 2. Most or all of the ducts are infiltrated by inflammatory cells; more than an occasional duct shows degenerative changes (nuclear pleomorphism, disordered polarity, cytoplasmic vacuolization).
- 3. As above, with most or all of the ducts showing degenerative changes or focal luminal disruption.

VENOUS ENDOTHELIAL INFLAMMATION

- 1. Subendothelial lymphocytic infiltration involving a minority of the portal and/or hepatic venules.
- 2. Subendothelial lymphocytic infiltration involving most or all of the portal and/or hepatic venules.
- 3. As above, with moderate to severe perivenular inflammation that extends into the perivenular regions, associated with perivenular liver cell necrosis.