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RESEARCH PRODUCT
Determining a healthy reference range and factors potentially influencing PRO-C3 – A biomarker of liver fibrosis
Daniel G.k. RasmussenPeder FrederiksenDiana Julie LeemingLise Lotte GluudElisabeth ErhardtsenJörn M. SchattenbergDiane E. ShevellM.a. KarsdalGuruprasad P AithalGuruprasad P. AithalGuruprasad P. Aithalsubject
NASH-CRN NASH Clinical Research NetworkBiopsyDiseaseAST aspartate aminotransferaseRC799-869Ethnic groupsGastroenterologyNIMBLE Non-Invasive Biomarkers of Metabolic Liver Disease (consortium)FibrosisImmunology and AllergyBody mass indexmedicine.diagnostic_testFatty liverNAS NAFLD Activity ScoreGastroenterologyDiseases of the digestive system. GastroenterologyHospitalsNPV negative predictive valueLiver biopsyBiomarker (medicine)Research Articlemedicine.medical_specialtyNAFLD non-alcoholic fatty liver diseaseADAM A Disintegrin and MetalloproteasesNASH non-alcoholic steatohepatitisReference rangeReference valuesAUROC area under the receiver operating characteristics curveInternal medicineALT alanine aminotransferaseBiopsyInternal MedicinemedicineHumansFIB-4 fibrosis-4Healthy volunteersHepatologyALP alkaline phosphatasebusiness.industryCLSI Clinical and Laboratory Standards InstituteT2DM type 2 diabetes mellitusELF™ test Enhanced Liver Fibrosis testmedicine.diseaseLITMUS Liver Investigation: Testing Marker Utility in Steatohepatitis (consortium)Collagen type IIIFibrosisPPV positive predictive valueReference standardsbusinessBody mass indexBiomarkersNon-alcoholic fatty liver diseasedescription
Background & Aims Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay. Methods PRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis. Results Robustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1–14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77–0.88], p <0.0001), and AUC = 0.79 (95% CI [0.73–0.85], p <0.0001), respectively). Conclusions The assay proved to be robust and sample stability was found to comply with hospital sample handling requirements. PRO-C3 measured in samples from patients with NAFLD/NASH was diagnostic for significant and advanced liver fibrosis. Lay summary We showed that PRO-C3 levels were stable under conditions conforming with hospital sample-handling requirements. We determined a healthy reference range and showed that PRO-C3 levels were not associated with sex, age, BMI, or ethnicity. Finally, we provide further evidence of an association of PRO-C3 with increasing liver fibrosis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-08-01 |