SAN FRANCISCO, November 12, 2018 – The clinical utility of quantitative metrics produced by MRCP+ for discriminating biliary disease was the focus of several abstracts accepted for presentation, here, at the American Association for the Study of Liver Disease’s The Liver Meeting® 2018, November 9-13, 2018 (Booth #611). Two abstracts highlight the use of Perspectum Diagnostics’ MRCP+ as a non-invasive technology for the evaluation of hepatobiliary diseases.
Accurate assessment of the biliary system is essential in diagnosis and monitoring of hepatobiliary diseases like Primary Sclerosing Cholangitis (PSC) and is integral to liver transplant preparation and post-transplant evaluation. Magnetic resonance cholangiopancreatography (MRCP) is used extensively in the evaluation of biliary tree anatomy. It is a non-invasive method for evaluating biliary disorders which provides information that increases diagnostic confidence while minimizing the frequency of invasive procedures. However, MRCP is not quantitative and has high subjectivity in reading.
Pending FDA clearance, MRCP+ is designed to allow existing MRCP data to be enhanced and quantitatively characterized using advanced image processing techniques. The technology enhances data from conventional MRCP without needing to inject contrast agent, enabling 3D visualization of ducts. MRCP+ calculates quantitative 3D biliary system models that enable measurement of bile duct widths and automatic detection of regions of variation of duct widths. MRCP+ includes tools for interactive segmentation and labelling of the biliary system and structures.
In the study, “Stratification of biliary disease with quantitative MRCP (MRCP+),” (Abstract #1952: Monday, November 12, 8am-5:30pm, part of session #1268: Cholestatic and Autoimmune Liver Diseases), researchers evaluated the potential clinical utility of the metrics produced by MRCP+ for discriminating biliary disease. Heavily T2-weighted MRCP images were acquired on a cohort of healthy, Autoimmune Hepatitis (AIH), Hepatitis C (HCV), Non-Alcoholic Fatty Liver Disease (NAFLD), Primary Biliary Cholangitis (PBC) and PSC subjects. These images were processed with MRCP+ to enhance and quantify the tubular biliary structures. The healthy common bile duct width reference intervals produced by MRCP+ were comparable to those previously reported in the literature and PSC patients had a significantly higher duct variability score than other cohorts. Demonstrating that a multi-scale image analysis method both enhanced and quantified biliary tubular structures, the results show that MRCP+ provides measures that could objectively differentiate patients with PSC (AUROC 0.94).
Sensitive and specific biomarkers for pediatric sclerosing cholangitis (SC) are lacking. Recently, Matrix Metalloproteinase 7 (MMP7) was shown to be expressed in bile duct epithelium in biliary atresia. In the study ““Matrix Metalloproteinase 7 (MMP7) as a Biomarker of Sclerosing Cholangitis in Pediatric Autoimmune Liver Disease.,” (Abstract #0183) MMP7 was researched as a novel biomarker in pediatric SC. MRCP+ was used to determine the percentage of biliary tree affected by strictures and dilatations (n=24).
Histologically, MMP7 levels correlated with the presence of periductal sclerosis (p<0.001) and lymphocytic cholangitis (p=0.040). The AUROC of MMP7 for predicting clinical diagnosis trended higher than that for ALP and GGT. MMP7 correlated with percentage of affected biliary tree determined by MRCP+ (r=0.43, p=0.043). Immunofluorescence (IF) localized MMP7 to cholangiocytes, linking MMP7 to biliary injury and fibrosis. This was corroborated by correlations between MMP7 levels and MRE (r=0.47, p=0.004) and histological parameters of inflammation and fibrosis as assessed by ISHAK grade (p=0.015), METAVIR stage (p=0.011) and Nakanuma score (p=0.046).
This study showed, with good correlation to MRCP+, that MMP7 is a promising biomarker for non-invasive diagnosis of PSC and ASC in children. We speculate that the excellent test performance originates from the role of MMP7 in both biliary injury and fibrosis, the drivers of SC.
This new data, presented at AASLD’s The Liver Meeting ® 2018, highlight the utility of quantitative MRCP, MRCP+, in assessing the usefulness of biomarkers such as MMP7, and also as a non-invasive technology for the stratification of hepatobiliary diseases.