Procollagen-3 N-Terminal Peptide (P3NP)

Raised serum concentrations of P3NP have been demonstrated in patients with liver fibrosis and cirrhosis of various aetiologies. Concentrations have been shown to correlate with histologically assessed fibrosis and the degree of hepatic fibrotic activity and inflammation. P3NP is not, however liver-specific and raised concentrations have been reported in various conditions where accumulation and/or degradation of collagen occur including myelofibrosis, systemic sclerosis, breast carcinoma with bony metastases and hyperthyroidism.Methotrexate is a valuable drug in the treatment of severe psoriasis but the development of hepatic fibrosis in some patients may necessitate its withdrawal. Fibrosis and cirrhosis may develop without detectable changes in liver enzymes, and neither radionuclide nor ultrasound examination are sufficiently sensitive or specific to detect fibrosis reliably. Liver biopsy is accepted as the definitive test for hepatic fibrosis, but is associated with a small risk of morbidity and mortality. As hepatic fibrosis induced by methotrexate appears to be associated with long-term treatment, as previous guidelines proposed that a liver biopsy be performed after a cumulative dose of methotrexate of 1.5 g (approx. every 18 months). Since psoriatic patients may require repeated biopsies during the course of prolonged treatment with methotrexate, a serological test reflecting hepatic fibrosis would be of great value.During liver fibrosis there is an increase in hepatic collagen, predominantly of type III. Collagen molecules are derived from procollagen by cleavage of terminal peptides, which are released into serum. Recent studies demonstrated the value of measuring serum P3NP (Intact N-terminal pro-peptide of type III collagen) in assessing the extent of liver damage from methotrexate. It was concluded that patients whose serum P3NP concentration are consistently normal are very unlikely to have significant liver damage, and the follow-up biopsy may be restricted to the small minority in whom serum P3NP concentration are repeatedly elevated. Serum P3NP should be performed at least every three months and liver biopsy should then be considered only for those patients in whom it is persistently abnormal (> 4.2 µg/L).