Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients

Abstract

This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP-O and PIIINP-B) and laminin P1 (LamP1-B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long-term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal, (2) steatosis, (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3-5 were considered to show clinically relevant abnormality. Compared with controls, PIIINP-O was significantly raised in the group of MTX-treated psoriatics (P < 0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P < 0.0001). In contrast, PIIINP-B and LamP1-B did not distinguish between controls and MTX-treated patients or between histological groups. Forty-two patients had two or more biopsies with simultaneous PIIINP-O measurement. PIIINP-O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP-O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP-O was measured 3-monthly for up to 6 years during MTX treatment. PIIINP-O was elevated at some time during follow-up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal. Our findings indicate that PIIINP-O is of value in detecting liver damage and, particularly if measured serially, may reduce the need for liver biopsy in MTX-treated patients. Although the test does not detect all patients with fibrosis, it would appear that the risk of missing significant liver damage in patients with persistently normal PIIINP-O is low.

Dermatologists’ Adherence to the Guideline of the Dutch Society of Dermatology and Venereology with Respect to the Treatment with Methotrexate for Severe Chronic Plaque Psoriasis: Results from a Dutch Survey

“…Performing a liver biopsy only in patients with an abnormal PIIINP resulted, according to the study of Maurice et al [14], in a 45% reduction of all liver biopsies and the study of Chalmers et al [13 ]in a sevenfold reduction, without important liver damage being missed. Boffa et al [15 ]and Zachariae et al [8, 16, 17 ]also concluded that the chance to develop substantial liver fibrosis and the risks of missing significant liver damage are minimal in case of persisting normal PIIINP values.…”

Methotrexate-lnduced Liver Cirrhosis

“…In more recent years. PIIINP has been studied further in psoriatics on MTX [11][12][13], Also these studies indicated its value for measuring abnormal hepatic fibrogenesis.…”

Análisis del resultado de pruebas hepáticas en pacientes psoriáticos tratados con metotrexato: Estudio retrospectivo

“…En Europa, 20% de los dermatólogos lo usa rutinariamente para la detección de fibrosis hepática secundaria a metotrexato 9 , lo que lleva a que la monitorización con pruebas hepáticas se realice más espaciada, esto es cada 2 meses o más. Se recomienda controlar niveles de PIIIP cada 3 meses durante un tratamiento continuo de metotrexato 28,29 , con indicación de biopsia, sólo en caso de niveles persistentemente altos 21 . Esto ha logrado disminuir 7 veces la necesidad de biopsia hepática en paciente psoriáticos tratados con metotrexato, con un costo menor y la preferencia de los pacientes 26 .…”