Pathology Handbook

Procollagen III N-peptide


Procollagen, PIIINP, P3NP

Clinical Indications

Monitoring for hepatic fibrosis, particularly in patients receiving methotrexate treatment who should be checked at three to six month intervals.

Methotrexate is a successful form of treatment for psoriasis and rheumatoid arthritis (RA).  It has, however, been noted that prolonged exposure can result in irreversible hepatic fibrosis the risk of which is idiopathic but associated with cumulative doses of more than 1.5g (usually encountered in psoriasis as lower doses are used in RA). Previously it was advised that a liver biopsy be considered after each cumulative 1.5g methotrexate.  In 1996 it was shown that serum P3NP concentrations were predictive of the development of hepatic fibrosis. Continually raised P3NP concentrations were found to be associated with fibrosis in 78-100% of cases, but were only seen in 15-18% of subjects with a normal liver on biopsy. Current guidelines on the use of methotrexate in psoriasis suggest P3NP measurements be carried out annually and three monthly after a raised value.

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Analysed by referral laboratory if specific criteria met.

Specific Criteria

Patient on methotrexate therapy

Turnaround Time

Two to three weeks


Serum in Gold Top (SST)


2 mL


Vacutainer gold top

Causes for Rejection

  • Unlabelled sample
  • Prolonged delay in reaching the laboratory
  • Sample in SST tube
  • Assay performed within the previous three months

Reference Range

Adult (20 - 65 years) < 4.2 µg/L

Levels are higher levels in young people due to growth


PIIINP is a sensitive indicator of hepatic fibrosis, but may be raised in other conditions, particularly active connective tissue disease.

A liver biopsy should be considered if:

  • there are three P3NP levels above 4.2 ug/L or
  • two levels above 8.0 ug/L over a 12 month period.
  • A liver biopsy should also be considered if the pre-treatment level is above 8.0 ug/L.

Consider withdrawing methotrexate if 3 samples > 10.0 μg/L in a 12 month period