PIIINP (P3NP; Procollagen 3 N-terminal peptide)
PIIINP is the amino terminal peptide of type III procollagen, released during the synthesis and deposition of type III collagen. PIIINP in the serum can be derived from the synthesis of new type III collagen or from the degradation of existing type III collagen fibrils.
There is evidence for dermatology patients that serum PIIINP measurement is a useful non-invasive test for the detection and monitoring of methotrexate-induced liver fibrosis and cirrhosis, and serial measurements may reduce the need for liver biopsy.
Note that PIIINP can be raised following bone fracture and also in rheumatology patients as it can be falsely elevated in inflammatory arthritis and so is not recommended routinely in these patients.
This test is not useful in paediatric patients (<18 years of age) due to raised levels associated with growth.
For adults, 5 ml of blood taken into a narrow gold top tube (or rust top for the Acute Unit) sent immediately (less than 1 hour) to the laboratory.
Do not store but send immediately to the laboratory (less than 1 hour).
Relevant clinical details including whether the sample is for pre-treatment investigations for psoriasis or if the patient is currently being treated with methotrexate for dermatological causes.
The samples are sent for analysis to King's College Hospital, London with results expected back within 2 weeks.
Adult (>19 years) PIIINP reference range: 1.2 - 4.2 ug/L
Consider liver biopsy in adult patients treated with methotrexate for psoriasis if PIIINP is:
- > 8.0 µg/L Pre-Treatment
- >8 ug/L on two occasions; or
- >4.2 ug/L but <8 ug/L on three occasions within 12 months;
- >10ug/L on one occasion
as these results may indicate liver fibrosis. Suggest onward referral for specialist advice.
Note: Increased extrahepatic collagen turnover (e.g. active erosive arthritis or bone fractures) may also cause raised PIIINP)
The decision whether to perform liver biopsy, withdraw or continue treatment despite raised PIIINP must also take into account other factors such as patient age, disease severity, and the ease with which alternative therapies may be used in place of methotrexate. (BSR/BHPR guidelines)
No guidelines are currently available for further investigations in children - PIIINP levels may reflect both hepatic fibrogenesis and also general growth.
BSR/BHPR guidelines for DMARD therapy 2008