Diana Feier

Liver Fibrosis: Histopathologic and Biochemical Influences on Diagnostic Efficacy of Hepatobiliary Contrast-enhanced MR Imaging in Staging

PURPOSE To evaluate the diagnostic performance of gadoxetic acid-enhanced magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with diffuse chronic liver diseases (CLDs) and to investigate the factors that may influence the results. MATERIALS AND METHODS With the approval of the Hospital Ethics Committee and waiver of the informed consent requirement, data in 102 patients with histologically proven liver fibrosis (classified according to the METAVIR system) of various underlying causes were retrospectively analyzed. Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of the liver was defined by using region of interest measurements before contrast material injection and in the hepatobiliary phase (20 minutes after contrast material administration), and relative enhancement was calculated. Univariate and multivariate regression analyses were applied to identify variables associated with relative enhancement measurements, and the performance of relative enhancement measurements in the staging of liver fibrosis was assessed by using area under the receiver operating characteristic curve (AUC) analysis. RESULTS At analysis of the relationship between enhancement measurements and histologic parameters, the relative enhancement values correlated strongly with liver fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P = .05). In multivariate analysis, only liver fibrosis stage independently influenced relative enhancement values (P < .001). The measurements performed well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and 0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels were independent predictors of false-negative results. CONCLUSION The presence of hepatic fibrosis can be assessed with good discrimination by using gadoxetic acid-enhanced MR imaging, but assessment can be confounded in the setting of abnormal aspartate aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

Noninvasive Differentiation of Simple Steatosis and Steatohepatitis by Using Gadoxetic Acid–enhanced MR Imaging in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study

PURPOSE To determine whether gadoxetic acid-enhanced magnetic resonance (MR) imaging can be used to distinguish between simple steatosis and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD), defined according to the steatosis activity and fibrosis (SAF) scoring system, which is based on the semiquantitative scoring of steatosis activity and liver fibrosis. MATERIALS AND METHODS The local institutional review committee approved this study and waived written informed consent. This was a retrospective study of gadoxetic acid-enhanced 3-T MR imaging performed in 81 patients with NAFLD (45 men [56%]; mean age, 56 years; range, 25-78 years). The MR images were analyzed by using the relative enhancement (the ratio of signal intensities of the liver parenchyma before and 20 minutes after intravenous administration of gadoxetic acid). Univariate and multiple regression analyses were applied to identify variables associated with relative enhancement measurements. The ability of relative enhancement to allow differentiation between simple steatosis and NASH was assessed by using area under the receiver operating characteristic (ROC) curve analysis. RESULTS Relative enhancement negatively correlated with the degree of lobular inflammation (r = -0.59, P < .0001), ballooning (r = -0.44, P < .0001), and fibrosis (r = -0.59, P ≤ .0001), but not with steatosis (r = -0.16, P = .15). Patients with NASH had a significantly lower relative liver enhancement (0.82 ± 0.22) than those with simple steatosis (1.39 ± 0.52) (P < .001). Relative enhancement measurements performed well in the differentiation between simple steatosis and NASH, with an area under the ROC curve of 0.85 (95% confidence interval: 0.75, 0.91) (cutoff = 1.24, sensitivity = 97%, specificity = 63%). CONCLUSION Gadoxetic acid relative enhancement was significantly lower in patients with NASH than in patients with simple steatosis, but further prospective studies are warranted.

Morphologic and Molecular Features of Hepatocellular Adenoma with Gadoxetic Acid–enhanced MR Imaging

PURPOSE To evaluate the diagnostic performance of imaging features of gadoxetic acid-enhanced magnetic resonance (MR) imaging to differentiate among hepatocellular adenoma (HCA) subtypes by using the histopathologic results of the new immunophenotype and genotype classification and to correlate the enhancement pattern on the hepatobiliary phase (HBP) with the degrees of expression of organic anion transporting polypeptide (OATP1B1/3), multidrug resistance-associated protein 2 (MRP) (MRP2), and MRP 3 (MRP3) transporters. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent waived. MR imaging findings of 29 patients with 43 HCAs were assessed by two radiologists independently then compared with the histopathologic analysis as the standard of reference. Receiver operating characteristic curves and Spearman rank correlation coefficient were used to test the diagnostic performance of gadoxetic acid-enhanced MR imaging features, which included the retention or washout at HBP and degree of transporter expression. Interreader agreement was assessed by using the κ statistic with 95% confidence interval. RESULTS The area under the curve for the diagnosis of inflammatory HCA was 0.79 (95% confidence interval: 0.64, 0.90); for the steatotic type, it was 0.90 (95% confidence interval: 0.77, 0.97); and for the β-catenin type, it was 0.87 (95% confidence interval: 0.74, 0.95). There were no imaging features that showed a significant statistical correlation for the diagnosis of unclassified HCAs. On immunohistochemical staining, OATP1B1/3 expression was the main determinant for the retention, whereas MRP3 was the key determinant for washout of gadoxetic acid at HBP (P < .001). MRP2 appeared to have no role. CONCLUSION Gadoxetic acid-enhanced MR imaging features may suggest the subtype of HCA. The degree of OATP1B1/3 and MRP3 expression correlated statistically with gadoxetic acid retention and washout, respectively, in the HBP.

Susceptibility-weighted MR Imaging in the Grading of Liver Fibrosis: A Feasibility Study

PURPOSE To assess the feasiblity of magnetic resonance (MR) susceptibility-weighted (SW) imaging as a tool to evaluate liver fibrosis grades in patients with chronic liver diseases (CLD) utilizing signal intensity (SI) measurements, with histopathologic findings as the reference standard. MATERIALS AND METHODS This retrospective study was approved by the local ethics committee. All subjects gave written informed consent. Eighty consecutive patients (mean age, 56.8 years), 60% of whom were male [n = 48] and 40% of whom were female [n = 32], with CLD due to various underlying causes and histopathologically proved liver fibrosis were included. Biopsies were evaluated for liver fibrosis and necroinflammatory activity (according to METAVIR scoring system), iron load, and steatosis. Two radiologists, blinded to the clinical data, assessed regions of interest in the liver and spinal muscle in consensus. Liver-to-muscle SI ratios were calculated and correlated to histopathologic findings and clinical data by using univariate and multivariate regression analysis. RESULTS Liver-to-muscle SI ratio decreased in parallel with the increasing grade of liver fibrosis and correlated strongly with liver fibrosis (r = -0.81, P < .0001) and moderately with necroinflammatory activity (r = -0.52, P < .0001) and iron load (r = -0.37, P = .0002) but did not correlate with steatosis (r = -0.18, P = .11). In multiple regression analysis, liver fibrosis and iron load independently influenced SW imaging measurements, explaining 69% of the variance of liver-to-muscle SI ratio (R(2) = 0.69, P < .001). Liver-to-muscle SI ratio performed well in grading liver fibrosis, with an area under the receiver operating characteristic curve of 0.92 for scores of F2 or higher and 0.93 for score of F4 (liver cirrhosis). CONCLUSION SW imaging is a feasible noninvasive tool to detect moderate and advanced liver fibrosis in CLD patients.

Non-Invasive Evaluation of Liver Steatosis, Fibrosis and Cirrhosis in Hepatitis C Virus Infected Patients Using Unidimensional Transient Elastography (Fibroscan®)

Chronic conditions of the liver represent an important public health issue. Whatever the na‐ ture of the aggression against the liver, it seems that it always follows the same pattern: in‐ flamation -> necrosis -> healing (fibrosis) -> regeneration (cirrhosis) -> dysplasia -> hepatocellular carcinoma. An important link in this course of events is represented by fibro‐ genesis. On the other hand, there are more and more evidence that, in patients with chronic hepatitis C, steatosis is a risk factor independently associated with necroinflammatory activ‐ ity and fibrosis progression.