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Classification for Liver Biopsy Findings in Patients Receiving Methotrexate Therapy

Purpose: To evaluate a liver biopsy for changes associated with methotrexate hepatotoxicity using the Roenigk classification scheme.

Description

Chronic methotrexate therapy may result in serious hepatotoxicity. Roenigk et al used a grading scheme to classify the severity of injury seen on liver biopsy. This can help determine how methotrexate therapy is to be continued.


 

Parameters:

(1) fatty infiltration

(2) nuclear variability

(3) portal tract inflammation

(4) portal tract expansion

(5) hepatocellular necrosis

(6) fibrosis

 

The original histologic grading scheme is as follows:

Histologic Findings

Grade

normal, or

fatty infiltration (mild), and/or

nuclear variability (mild), and/or

portal tract inflammation (mild)

I

fatty infiltration (moderate to severe) or

nuclear variability (moderate to severe) or

portal tract inflammation (moderate to severe) or

portal expansion (moderate to severe) or

hepatocellular necrosis (spotty)

II

fibrosis (mild)

III-A

fibrosis (moderate to severe)

III-B

cirrhosis

IV

 

where:

• Fibrosis = formation of fibrotic septa extending into the lobules and connecting portal tracts. This is usually evaluated using a trichrome and/or reticulin stain.

• Fibrosis limited to the portal tracts without disruption of the limiting plates and without septa formation is not considered grade III (I would call this grade II)

• Cirrhosis = severe septal fibrosis and regenerative hepatocellular nodules

• Hepatocellular necrosis: According to Roenigk page 147 moderate-to-severe necrosis is Grade II, yet Figure 4 page 151 shows focal liver cell necrosis as grade III. Erickson reports Grade II as including severe, spotty hepatocellular necrosis. I would think more extensive necrosis might be considered grade III.

 

A revision of this table is:

 

Parameter

Finding

Class

fatty infiltration

none

I

 

mild

I

 

moderate or severe

II

nuclear variability

none

I

 

mild

I

 

moderate or severe

II

portal tract inflammation

none

I

 

mild

I

 

moderate or severe

II

portal expansion

none

I

 

mild

I

 

moderate or severe

II

spotty hepatocellular necrosis

none

I

 

moderate to severe spotty necrosis

II

fibrosis

none

I

 

limited to portal triads without disruption of the limiting plate

II

 

mild

III-A

 

moderate to severe

III-B

 

cirrhosis

IV

 

where:

• Normal is "none" for all 6 parameters.

 

Grade =

= MAX(class for the 6 histologic parameters)

 

Recommendations in 1982 based on liver biopsy findings

 

Grade

Therapy Recommendations

I

continue to receive

II

continue to receive

III-A

may continue to receive therapy, but should have a repeat liver biopsy after 6 months of continuous methotrexate therapy

III-B

usually should not receive further therapy

IV

usually should not receive further therapy

 

Under exceptional circumstances a patient with Grade IIIB or IV changes may need to have the therapy continued. These patients require very careful followup.

 


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Specialty

Objective

ICD-10