MR elastography of liver disease: State of the art

Abstract

Hepatic fibrosis is a common result of different chronic liver diseases caused by viral infections, alcohol abuse, nonalcoholic fatty liver disease (NAFLD), autoimmune disease and metabolic/genetic disorders. Hepatic fibrosis is a dynamic process which can, in some cases, be reversible with effective treatment (1, 2). Otherwise, it can progress to more advanced stages including cirrhosis where liver function is impaired and severe complications can occur such as variceal bleeding, ascites, portal hypertension, hepatocellular carcinoma and death (3). In 2009, chronic liver disease and cirrhosis were responsible for 143,000 hospitalizations, 11,000 in-hospital deaths (7.7% death rate), and 6.7 billion dollars of hospital charges in total (4). Accurately detecting and staging fibrosis is important in the management of chronic liver disease for initiating treatment and monitoring its effects on the liver. Chronic viral hepatitis C (HCV) infection is a significant cause of hepatic disease and its treatment may depend on the presence of substantial fibrosis (5, 6). It is well known that liver biopsy is the current reference method for the detection and staging of fibrosis. However, it is an invasive method and can cause undesired complications including bleeding (1.7%) (7) and death (0.01-1%) (7-9). The accuracy of liver biopsy is affected by sampling errors (20-33% of patients can have fibrosis stage misclassified by 1 category) (10, 11), and intra- and inter-operator inconsistency (Kappa coefficient 0.62 – 0.89, where 1 means perfect agreement) (11, 12). Furthermore, this approach is not well accepted by patients and physicians alike (13). Conventional noninvasive imaging techniques (ultrasound, computed-tomography, MRI) can visualize the morphologic changes of liver due to fibrosis and cirrhosis. However, the sensitivity and accuracy of these modalities are low for detecting earlier stages of fibrosis and thus are not suitable for staging liver fibrosis over its entire spectrum (14). Over the last several years, new noninvasive methods of assessing liver fibrosis have been developed and investigated, including serum tests, diffusion-weighted MR imaging (DWI), contrast enhanced MR imaging (CE-MRI), ultrasound based transient elastography (UTE) and MR elastography (MRE). Accumulated data showed that the AUROC (area under receiver operating characteristic curve) values are between 77%-91% for serum tests (15-20), 88% for DWI (21), and 83% for CE-MRI (22) to detect the presence of liver fibrosis due to different disease causes. As one of the two existing methods of measuring liver stiffness, UTE has higher AUROC values (0.79-0.98) (23-25), yet it is less accurate for detecting early fibrosis stages and has a high technical failure rate in certain patient subsets (ascites, narrow intercostals space, obesity) (26-28). The other method of measuring liver stiffness, MR elastography (MRE) is the most accurate (AUROC = 92% - 100%) method for detecting and staging liver fibrosis to date, especially in early stages of fibrosis because of its capability of measuring cross-sectional areas of hepatic parenchyma, and the technique is not affected by the ascites and obesity (3, 21, 26, 27, 29-31). In one study, MRE even detected necroinflammation before the onset of fibrosis in patients with NAFLD (32). The detection of early stage fibrosis is of clinical significance as treatments for liver disease are thought to be more effective when compared to later stages of fibrosis. Given its technical advantages and high diagnostic accuracy, this article reviews the application of MR elastography to address clinical questions involving HCV, NAFLD, and methotrexate (MTX) exposure.