Fowler, Kathryn J.

Background: Qualification of non-invasive tests (NITs) and blood biomarkers for fibrosis severity and risk assessment is an unmet need in clinical care for cirrhosis. The paucity of reproducibility data for imaging and blood biomarkers in cirrhosis hinders their application for longitudinal monitoring. The aim of this study was to evaluate the reproducibility of imaging and blood biomarkers in a prospective cohort of adults with cirrhosis. Methods: We prospectively enrolled adults with cirrhosis in an observational, longitudinal cohort study. Participants completed a research visit with vibration-controlled transient elastography (VCTE) with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and blood testing, including AST, ALT, platelets, alpha-fetoprotein (AFP), and the Fibrosis-4 Index (FIB-4). Biomarkers were repeated a median of 3 months apart without any interim intervention. The primary outcome was the reproducibility of each biomarker as assessed by the reproducibility coefficient (RDC%), within-participant coefficient of variation (wCV), intraclass correlation coefficient (ICC), and Bland–Altman analysis. Results: In total, 40 participants (mean age 62, 60% female, mean BMI 28.6 kg/m 2 ) had VCTE/CAP, 38 AST/ALT, and 26 had AFP at both time points. The RDC% for VCTE-LSM was 54.4, wCV 0.19, and ICC 0.91. VCTE CAP had an RDC% of 56, a wCV of 0.30, and ICC 0.47. AFP had an RDC% of 58, a wCV of 0.21, and an ICC of 0.95. RDC% for AST, ALT, and FIB-4 ranged from 70% to 79%. On Bland–Altman analyses, VCTE-LSM demonstrated the lowest relative bias (0.4%). Conclusions: Prospective assessment of repeat biomarkers in adults with cirrhosis found that VCTE-LSM and CAP provide consistent assessments across individuals but may yield substantial within-individual variation. Blood-based biomarkers had poor reproducibility within individuals but were consistent in detecting between-patient variability. These data can inform ultrasound-based non-invasive testing qualification by defining thresholds that may reflect measurement variability rather than true biologic change over time.

Chronic liver disease (CLD) has rapidly increased in prevalence over the past two decades, resulting in significant morbidity and mortality worldwide. Historically, the clinical gold standard for diagnosis, assessment of severity, and longitudinal monitoring of CLD has been liver biopsy with histological analysis, but this approach has limitations that may make it suboptimal for clinical and research settings. Magnetic resonance (MR)-based biomarkers can overcome the limitations by allowing accurate, precise, and quantitative assessment of key components of CLD without the risk of invasive procedures. This review briefly describes the limitations associated with liver biopsy and the need for non-invasive biomarkers. It then discusses the current state-of-the-art for MRI-based biomarkers of liver iron, fat, and fibrosis, and inflammation.

Use of gadoxetate disodium, a hepatobiliary gadolinium‐based agent, in patients with chronic parenchymal liver disease offers the advantage of improved sensitivity for detecting hepatocellular carcinoma (HCC). Imaging features of liver observations on gadoxetate‐enhanced MRI may also serve as biomarkers of recurrence‐free and overall survival following definitive treatment of HCC. A number of technical and interpretative pitfalls specific to gadoxetate exist, however, and needs to be recognized when protocoling and interpreting MRI exams with this agent. This article reviews the advantages and pitfalls of gadoxetate use in patients at risk for HCC, and the potential impact on Liver Imaging Reporting and Data System (LI‐RADS) imaging feature assessment and categorization.Level of Evidence: 5Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2019;49:1236–1252.

Level of Evidence : 5 Technical Efficacy Stage : 3 J. Magn. Reson. Imaging 2018;47:1169–1171.