Histologic Grades of Three Key Changes

Steatosis

Hepatocyte Ballooning Injury

Lobular Inflammation

0 (<5%)

1 (5%-33%)

2 (>33%-66%)

3 (>66%)

0 (None)

1 (Few balloon cells)

2 (Many balloon cells)

0 (No foci)

1 (<2 foci per 200X field)

2 (2-4 foci per 200X field)

3 (>4 foci per 200X field)

Portal Inflammation

Score

Mostly lymphocytic inflammation involving, but not noticeably expanding, a minority of the triads

1

Expansion of most or all of the triads, by a mixed infiltrate containing lymphocytes with occasional blasts, neutrophils and eosinophils

2

Marked expansion of most or all of the triads by a mixed infiltrate containing numerous blasts and eosinophils with inflammatory spillover into the periportal parenchyma.

3

Bile duct injury

Score

A minority of the ducts are cuffed and infiltrated by inflammatory cells and show only mild reactive changes such as increased nuclear:cytoplasmic ratio of the epithelial cells.

1

Most or all of the ducts infiltrated by inflammatory cells. More than an occasional duct shows degenerative changes such as nuclear pleomorphism, disordered polarity and cytoplasmic vacuolization of the epithelium.

2

As above for 2, with most or all of the ducts showing degenerative changes or focal lumenal disruption.

3

Venous endothelial inflammation

Score

Subendothelial lymphocytic infiltration involving some, but not a majority of the portal and/or hepatic venules.

1

Subendothelial infiltration involving most or all of the portal and/or hepatic venules.

2

As above for 2, with moderate or severe perivenular inflammation that extends into the perivenular parenchyma and is associated with perivenular hepatocyte necrosis.

3

* The activity index is the sum of the scores of all three changes, and is used to determine whether allograft rejection is present.

Rejection Category

Histologic Features (Liver Allograft Acute Cellular Rejection)

None (A0)

No rejection (i.e. absence of the defined portal inflammation, ductulitis and endothelioitis).

Indeterminate

Portal inflammatory infiltrate that fails to meet the criteria for the diagnosis of acute rejection.

Mild (A1)

Infiltrate in a minority of the triads, that is generally mild, and confined within the portal spaces

Moderate (A2)

Infiltrate expanding most or all of the tracts

Severe (A3)

Infiltrate in some or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis

Category

Histologic Features

Mild

(Grade 1)

Mild portal inflammatory changes with patchy distribution.

Mild bile duct damage and venous endotheliitis.

Moderate

(Grade 2)

Conspicuous portal inflammatory changes with widespread distribution.

Moderate bile duct damage and venous endotheliitis.

Severe

Grade 3)

Marked portal inflammation, bile duct damage and venous endothelialitis.

Periportal inflammation, sinusoidal endotheliitis, hepatocelluar necrosis and arteritis may be present

Note

The severity of 1) portal inflammation, 2) bile duct damage, and 3) venous endothelial inflammation are graded on a scale of 0 = none to 3 = severe and are then collated to provide a final rejection grade. In some cases additional features, which are seen inconsistently in acute rejection (eg. portal inflammatory spillover, sinusoidal endotheliitis, parenchymal inflammation ± necrosis, arteritis), may be used to upgrade the overall severity of acute rejection.

Category

Histologic Features

B1

(Early or Mild)

Bile duct loss, without centrilobular cholestatis, perivenular sclerosis, hepatocyte ballooning or necrosis and dropout

B2

(Intermediate/moderate)

Bile duct loss, with one of the following four findings: centrilobular cholestasis, perivenular sclerosis, hepatocellular ballooning, necrosis and dropout

B3

(Late or severe)

Bile duct loss, with at least two of the following four findings: centrilobular cholestasis, perivenular sclerosis, hepatocellular ballooning, centrilobular necrosis and dropout

Note

Bile duct loss in > 50% of triads must be present for the diagnosis.