We have introduced a routine assay for amino-terminal pro-peptide of type III procollagen (P3NP) for routine screening for methotrexate-induced liver fibrosis.
Methotrexate-induced liver disease is an important complication in patients treated with this drug. Current guidelines for treatment recommend the performance of liver biopsies when the cumulative dose reaches 1.5 g and serially at cumulative doses of 1.0 to 1.5 g doses thereafter. Owing to the fact that liver biopsies are associated with morbidity (and cost), several attempts have been made to screen non-invasively for liver fibrosis and cirrhosis.
A study published in the British Journal of Dermatology (2001 : 143 : 100-103) was designed to evaluate whether consistently normal serial serum P3NP levels would indicate that no significant fibrosis was occurring in the liver and thereby reduce the need for repeated liver biopsies in psoriatics on Methotrexate. The most important conclusion from this study (based on the observation that no liver fibrosis was missed in 63 patients with consistently normal P3NP levels) was that as long as P3NP was consistently normal in serial investigations –there was minimal risk of developing substantial hepatic fibrosis. A value higher than 4.2 ug/L was considered pathological.
It is worth noting that P3NP is NOT organ specific and does not reflect earlier liver damage – it reflects fibrogenesis. Other hepatotoxic drugs such as alcohol can also cause fibrosis and cirrhosis. P3NP can also be raised in a number of conditions such as thyroid disease, hepatitis, severe untreated haemochromatosis and biliary cirrhosis.
This test is not intended to replace liver biopsy, which is still the most reliable tool to establish morphological liver status. Patients from recognised risk groups (pre-existing disease, previous intake of hepatotoxins – including alcohol abuse, impaired renal function, diabetes and obesity) need to have morphological status established early, and may still need repeated biopsies after 1.5 g repeated dose. It is suggested that biopsy may be omitted when P3NP levels continuously show normal levels.
Current regimen is to perform P3NP after the patient has been treated with a cumulative dose of 1.5 g and perform a liver biopsy if deemed necessary.
Can be added on to an existing request up to 4 days following sample receipt
Chemical Pathology Dept. General Hospital, Southampton.Tel 023 80 96709Specimen Labelling Procedure