Laboratory Test Reference Guide

Not more frequently than 3 monthly

Serum stable for 5 days in fridge.

Transport - Send Frozen 

2.3 - 6.4 ug/L

In a study ( Br J Derm 2001:143:100-103) no liver fibrosis was missed in 63 psoriatic patients taking methotrexate with a P3NP level consistently equal to or less than 4.2 ug/L. P3NP is a marker of scar formation and may be elevated transiently following acute tissue damage ( recommend follow-up 3 monthly) or persistently in chronic fibrotic conditions ( e.g myelofibrosis.)

P111NP

Testing is usually requested in patients taking methotrexate for psoriasis. However, P111NP is not specific for liver fibrosis.

Growth hormone and testosterone increase P111NP levels.

P111NP levels in patients < 19 years old (actively growing)  are significantly higher than in the adult population and should not be used as a marker of hepatic fibrosis in patients on long term methotrexate.

 Patients taking methotrexate are at risk for cirrhosis. P111NP is used as “rule out” test.  Elevations above 4.2 ug/L may reflect growth (in children) or any soft tissue damage, acute or chronic. Some examples of conditions associated with elevations include: idiopathic lung fibrosis, malignancies, myeloproliferative diseases, post myocardial infarction

The Manchester protocol states (1):

Where possible measure P111NP prior to starting methotrexate

Indications for considering a liver biopsy:

Pre-treatment P111NP > 8 ug/L

P111NP > 4.2 ug/L in at least 3 samples in a 12 month period

P111NP > 8 ug/L in two consecutive samples

Indications for considering withdrawal of methotrexate:

Elevation of P111NP > 10 ug/L in at least 3 samples in a 12 month period

The decision whether to perform liver biopsy, withdraw treatment or continue treatment despite raised P111NP levels must also take into account other factors such as disease severity, patient age and the ease with which alternative therapies may be used in place of methotrexate .

P111NP reflects the production of Type 111 Collagen

The predominant form of collagen is Type 1. In adult skin, about 80% is type 1 and 20% type 111 collagen. During the initial period of wound healing, there is increased expression of Type 111 collagen. Type 111 collagen is found in soft tissues, none is present in bone. P111NP is a non-specific marker of soft tissue injury. Growth hormone and testosterone supplementation increases P111NP levels (2)

Adult reference interval (from vendor) is 2.3 – 6.4 ug/L

The cut-off used in clinical studies is 4.2 ug/l. This cut-off is based on an earlier reference interval study (no change in the assay).

Reference intervals reported in patients < 19 years old are (3):

1)    Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis. Chalmers RJ. Et al. See comment in PubMed Commons belowBr J Dermatol. 2005 Mar;152(3):444-50

2)    N-Terminal Propeptide of Type III Procollagen as a Biomarker of Anabolic Response to Recombinant Human GH and Testosterone. Shalender Bhasin, E. et al. JCEM 4224 – 4233. 2009

3)    Serum concentrations of carboxyl-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxyl-terminal telopeptide of type I collagen, and their interrelationships in schoolchildren. Patricia M. Crofton, Jean C. Wade, Mervyn R. H. Taylor, Celia V. Holland. Clin Chem 1577 – 81. 1997

Stephen du Toit, Chemical Pathologist 4 November 2016

Patients should be tested not more frequently than 3 monthly.

0.6 mL serum or plasma