Transient elastography in nonalcoholic fatty liver disease: Making sense of echos

Nonalcoholic fatty liver disease (NAFLD) is present in up to 30% of Americans and 25% of Asians and therefore is present in millions of individuals, making it the commonest liver condition in the world.1,2 From a hepatologist’s viewpoint, the task of evaluating and treating this enormous population is frightening! Fortunately, the large majority of individuals with NAFLD will not develop liver-related morbidity or die from their liver disease.3 Thus, the difficulty facing the managing physician is predicting which patients are at greatest risk of developing cirrhosis, thus identifying those who will benefit most from specific treatments, more intensive therapy, and monitoring. Natural history cohort studies have provided us some information on prognostic factors in patients with NAFLD.3-5 Comorbid diabetes is associated with increased all-cause and liver-related mortality rates.3,4 Diabetes and obesity have also been associated with higher rates of fibrosis progression.6,7 Unfortunately, given the high rates of obesity and diabetes among patients with NAFLD and the prevalence of these conditions in the general community, these clinical factors are not sufficiently specific to predict those who will develop cirrhosis or its complications. A more direct measure of prognosis is liver histology. Several studies have demonstrated that hepatic steatosis without evidence of inflammation or fibrosis is associated with low liver-related death rates of 0%-3% over a one-to two-decade period.4,8,9 In contrast, subjects with nonalcoholic steatohepatitis (NASH) are more likely to develop morbidity, with a cohort study of 131 subjects demonstrating a liver-related death rate of 17.5% over nearly two decades of follow-up.4 In this study, the hazard ratio for liver-related mortality associated with NASH was twice that compared to diabetes (13.9 versus 6.7, respectively), reinforcing the prognostic significance of histological assessment.4 However, it is not entirely clear whether the prognostic significance of NASH stems from the presence of steatohepatitis defined by lobular inflammation and ballooning or from the associated fibrosis. For example, Ekstedt et al. found that 18% of patients with NASH and portal fibrosis at baseline developed end-stage liver disease over time, whereas no patient with NASH decompensated in the absence of portal fibrosis.5 Liver biopsy is currently the accepted standard for determining the presence of NASH and fibrosis, but has well-documented problems of sampling and interpretation variability as well as procedural-related complications. These limitations have led to the development of noninvasive methods of histological assessment including clinical, biochemical, and radiological methods.10,11 Simple clinical indices such as body mass index (BMI) and diabetes have been combined with simple liver function tests12 as well as more direct markers of fibrogenesis (hyaluronic acid, tissue inhibitor of metalloproteinase-1)13 or apoptosis (cytokeratin-18), to predict different degrees of liver injury and fibrosis.14 In contrast, transient elastography (TE) uses sonic detection of liver stiffness to predict hepatic fibrosis. It has been validated in patients with chronic hepatitis C as an accurate predictor of cirrhosis. In this issue of HEPATOLOGY, Wong and colleagues present a much anticipated study examining the accuracy of TE among patients with NAFLD.15 The study population consisted of 246 individuals originating from two centers in France and Hong Kong who underwent liver biopsy and TE. Liver stiffness increased significantly with fibrosis and provided a high level of accuracy for detecting significant fibrosis (defined as at least perisinusoidal and portal/periportal fibrosis), advanced fibrosis (septal or bridging fibrosis) and cirrhosis, with area under the receiver operator characteristic (AUROC) curve values of 0.84, 0.92, and 0.97, respectively. Importantly, in subjects in whom a full set of 10 successful readings could be obtained, the accuracy of TE was not affected by BMI or steatosis grade. Prior reports of falsely high readings due to acute hepatitis16 were not observed, with accuracy not influenced by alanine aminotransferase (ALT) levels or the histological Abbreviations: AUROC, area under the receiver operator characteristic; BMI, body mass index; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NPV, negative predictive value; PPV, positive predictive value; TE, transient elastography. Address reprint requests to: Associate Professor Leon Adams, School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Verdun St, Nedlands, WA 6009, Australia. E-mail: leon.adams@uwa.edu. au; fax: 011 618 9346 3098. Copyright © 2009 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.23422 Potential conflict of interest: The author is an employee of the University of Western Australia, which has a licensing agreement with Quest Diagnostics Inc. regarding the commercialization of a noninvasive marker of hepatic fibrosis.