August 2020
Dr Aarti Pema – Chemical Pathologist
Ampath | ampath.co.za
Biochemistry Background
- Type III collagen is a key component of connective tissue.
- P3NP (N-terminal procollagen-III peptide) is a cleavage product of type III collagen precursor.
- Formed in equimolar amounts to type III collagen.
- Serum P3NP levels reflect the rate of extracellular matrix synthesis or breakdown.
Clinical Significance of P3NP
- P3NP is a direct biomarker for diagnosis and prognosis of hepatic fibrosis.
- Elevated serum P3NP indicates active connective tissue proliferation in the liver.
Conditions associated with raised P3NP:
- Fibrosis
- Cirrhosis
- Chronic active hepatitis
- Acute hepatitis
- Alcoholic liver disease
- Primary biliary cirrhosis
P3NP in Methotrexate (MTX)-Induced Hepatic Fibrosis
- MTX is a known hepatotoxin used long-term in autoimmune and inflammatory skin diseases, including psoriasis.
- Long-term MTX in psoriasis is linked to a 22% increased risk of hepatic fibrosis.
- Psoriasis prevalence:
- 1–3% in Western Caucasians
- 0.65% in a black KwaZulu-Natal cohort
Comparative Utility of P3NP
- Liver biopsy remains the gold standard, but non-invasive options like P3NP and imaging are preferred for safety and cost-effectiveness.
- P3NP sensitivity: 77.3%
- P3NP specificity: 91.5%
Benefits of serial P3NP monitoring:
- Consistently normal levels = minimal risk of hepatic fibrosis
- Reduces the need for liver biopsy
Comparison to other tests:
- Standard liver function tests (LFTs):
- Sensitivity: 38%
- Specificity: 83%
- Fibrotest panel (α2-macroglobulin, apolipoprotein A1, haptoglobin, GGT, total bilirubin):
- Sensitivity: 83%
- Specificity: 61%
P3NP offers better specificity and uses a single analyte.
Monitoring Guidelines for Psoriasis Patients on MTX
Pre-treatment testing:
- If P3NP > 1.00 U/mL (> 8 µg/L):
- Do not start MTX
- Refer for hepatology opinion
- Consider liver biopsy
During MTX treatment:
Refer to hepatology or consider liver biopsy if:
- P3NP > 1.25 U/mL (> 10 µg/L) on one occasion
- P3NP > 1.00 U/mL (> 8 µg/L) on two consecutive occasions
- P3NP > 0.53 U/mL (> 4.2 µg/L) on three occasions within 12 months
Consider stopping MTX if:
- P3NP > 1.25 U/mL (> 10 µg/L) on three occasions in a 12-month period
Other Causes of Raised P3NP
P3NP may also be elevated in:
- Pulmonary fibrosis
- Rheumatoid disorders
- Myocardial infarction
- Acromegaly
- Multiple trauma
- Active bone remodelling (e.g., after orthopaedic surgery, skeletal fractures)
- Erosive psoriatic arthritis
- Growing children
Not reliable for hepatic monitoring in the above scenarios.
📌 For more information or interpretation assistance, please contact your local Ampath pathologist.
✅ Ready when you are for the next Lab Update!
Continue Reading