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Procollagen III amino terminal propeptide (PIIINP): A marker of MTX induced liver fibrosis in rheumatoid arthritis patients?

Neama M Lotfy, Noran O El-Azizi, Marwa A Nassef, Hanaa A Amer, Hala G Mohamed, & Amany M Mansour

Background: to evaluate the reliability of serum Procollagen III aminoterminal peptide (PIIINP) in the screening for hepatic fibrosis induced by long term Methotrexate Therapy (MTX) in Rheumatoid Arthritis (RA) patients.

Methods and Findings: The study included 90 RA patients divided into 60 on MTX therapy (group I) and 30 on other medications (group II). All subjected to history taking, rheumatological examination and lab investigations including CBC, ESR, CRP, AST, ALT, RF and PIINP levels measurement, DAS score and Fibrosis-4 (FIB-4) score were calculated. Results showed significant lower disease duration, HCT, platelet count and higher MCV, AST, ALT, FIB-4 score, PIIINP level and more patients’ complaint of right hypochondrial pain in MTX intake group (p<0.05). ROC curve for PIIINP in group I showed that the cutoff level of >170 can detect MTX induced hepatic fibrosis with (51.52%) sensitivity and (92.59%) specificity, 89.5% PPV and 61% NPV. Correlation between PIIINP and all studied variables showed a significant positive correlation between PIIINP level and disease duration, MTX intake duration, MTX current and cumulative doses, MCV, AST, ALT, AST/ALT, FIB-4 score and significant negative correlation with folic acid intake, platelet count (P<0.05). A positive correlation found between cumulative MTX dose and FIB-4 score (P<0.001).

Conclusion: PIIINP can be used as screening noninvasive marker for MTX induced hepatic fibrosis in RA patients; it is positively correlated with AST/ALT ratio, FIB-4 score and cumulative MTX dose. Folic acid is protective against liver fibrosis in RA patients on MTX therapy.