N-terminal propeptide of procollagen type III (PIIINP) and methotrexate

In patients with psoriasis on methotrexate, measurement of procollagen III N-terminal peptide is advised as an indicator of hepatic fibrosis, although this is usually performed in secondarycare (1,2)

What is procollagen III N-terminal peptide?

• process of liver fibrosis is assumed to be caused by the excess production of extracellular matrix (ECM) in hepatic stellate cells (HSCs) (3,4)
• the increase of ECM deposited fragments in the Disse's space leads to liver injury
  • largest component of the ECM is collagen
  • in the liver type III collagen mainly occurs
• during the synthesis of type III collagen, the N-terminal propeptide of procollagen type III (PIIINP) is detached from procollagen type III
  • so the fibrogenesis results in release of ECM fragments into the blood
    • quantity of propeptide of procollagen type III can be a direct indicator of collagen synthesis and its deposition in the extracellular space
    • increased amount of propeptide of type III procollagen may indicate the transformation of normal liver tissue into connective tissue (1,2,3,4)

Notes (6):

• PIIINP is not a liver-specific marker
  • increased concentrations of PIIINP have also been other conditions associated with abnormal production of collagen
    • for example congestive heart failure, hypertension, coronary heart disease and pulmonary fibrosis

Reference:

• Spencer NJ et al. Blood test monitoring of immunomodulatory therapy in inflammatory disease. BMJ 2021; 372: n159 http ://dx .doi.org/ 10.1136/ bmj.n159
• Warren RB, Weatherhead SC, Smith CH, etal. British Association of Dermatologists'guidelinesfor the safe and effective prescribing of methotrexate for skin disease 2016.Br J Dermatol 2016;175:23-44. doi: 10.1111/bjd.14816
• Liu X, Wu H, Byrne M, et al. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Natl Acad Sci U S A. 1997;94:1852-6.
• Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209-18.
• Cross TJ, Calvaruso V, Maimone S, et al. Prospective comparison of Fibroscan, King’s score and liver biopsy for the assessment of cirrhosis in chronic hepatitis C infection. J Viral Hepat. 2010;17:546-54.
• Baranova A, Lal P, Birerdinc A, et al. Non-Invasive markers for hepatic fibrosis. BMC Gastroenterol. 2011;11:91-6.