Assessment of hepatic function employing hepatocyte specific contrast agent concentrations to multifactorially evaluate fibrotic remodeling

Abstract

Background: Diffuse parenchymal liver diseases are contributing substantially to global morbidity and represent major causes of deaths worldwide. The aim of our study is to assess whether established hepatic fat and iron quantitation and relaxometry-based quantification of hepatocyte-specific contrast material as surrogate for liver function estimation allows to evaluate liver fibrosis. Methods: Retrospective consecutive study. Seventy-two healthy patients (mean age: 53 years) without known liver disease, 21 patients with temporary elevated liver enzymes (mean: 65 years) and 109 patients with biopsy proven liver fibrosis or cirrhosis (mean: 61 years), who underwent liver magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent [gadoxetate disodium, gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), 0.25 mmol/mL Primovist, Bayer AG, Leverkusen, Germany] at 1.5 T (n=133) and at 3 T (n=69), were included. Fibrosis was classified using the histopathological meta-analysis of histological data in viral hepatitis (METAVIR) and the clinical Child-Pugh scores. Gd-concentration were quantified using T1 map-based calculations. Gd-concentration mapping was performed by using a Look-Locker approach prior to and 912±159 s after intravenous administration of hepatocyte specific contrast agent. Additionally, parenchymal fat fraction, R2*, bilirubin, gender and age were defined as predicting factors. Diagnostic accuracy was calculated in a monoparametric (linear regression, predictor: Gd-concentration) and multiparametric model (predictors: age, bilirubin level, iron overload, liver fat fraction, Gd concentration in the left and right liver lobe). Results: Mean Gd-concentration in the liver parenchyma was significantly higher for healthy patients ([Gd] =0.51 µmol/L) than for those with liver fibrosis or cirrhosis ([Gd] =0.31 µmol/L; P<0.0001) and with acute liver disease ([Gd] =0.28 µmol/L), though there were no significant differences for the latter two groups. There was a significant moderate negative correlation for the mean Gd-concentration and the METAVIR score (ρ=−0.44, P<0.0001) as well as for the Child-Pugh stage (ρ=−0.35, P<0.0001). There was a significant strong correlation between the bilirubin concentration and the Gd-concentration (ρ=−0.61, P<0.0001). The diagnostic accuracy for the discrimination of healthy patients and patients with known fibrosis or cirrhosis was 0.74 (0.71/0.60 sensitivity/specificity) in a monoparametric and 0.76 (0.85/0.61 sensitivity/specificity) in a machine learning based multiparametric model.