P1028 NON-INVASIVE SCORE SYSTEM FOR FIBROSIS (NISF) IN CHRONIC LIVER DISEASE: A NEW MODEL COMBINING BIOCHEMICAL, ELASTOGRAPHIC AND ULTRASOUND DATA

Abstract

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders characterised by hepatic steatosis, which may be benign (NAFL) or which may progress via inflammation and fibrosis to nonalcoholic steatohepatitis (NASH) and then to cirrhosis and liver failure. Liver biopsy is the standard diagnostic approach for NAFL/NASH. However it has limitations due to sampling site variability, cost and procedure-related morbidity. Appropriate NAFLD-specific circulating biomarkers may enable diagnosis, staging and monitoring of NAFL/NASH with fewer biopsies. Circulating fragments of cytokeratin-18 (K18), a marker of hepatocyte death, have been shown in several studies to indicate the transition from benign fatty liver to NASH, with a risk of fibrosis, in patients with NAFLD. Our goal was to develop a highly specific serum K-18 assay to monitor hepatic disease severity in patients with different stages of NAFLD. Methods: An assay to measure K18 fragments in serum using electrochemiluminescence (ECL) technology was developed using proprietary K18 fragment-specific antibodies: one labelled with an ECL-active ruthenium chelate reporter and a second antibody bound to paramagnetic beads. Results: Thirty known NAFL and NASH patient serums with assigned NAS scores were evaluated. K18 fragment concentrations in biopsy-proven NASH were elevated compared to NAFL (1232U/L and 345U/L respectively). The results also demonstrated good correlation with the M30 antibody assay. Conclusions: An ECL-based assay has been developed for the quantitation of serum K18 fragments. This new diagnostic test may enable routine monitoring in both central laboratories and physician’s offices of disease severity and progression in patients with NAFLD.