The use of acoustic radiation force-based shear stiffness in non-alcoholic fatty liver disease
Authors: Timothy James Scott Cross
Journal: Journal of Hepatology (2011)

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver diseaseJournal of HepatologyVol. 55Issue 3PreviewNonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening. Full-Text PDF Reply to: The use of acoustic radiation force-based shear stiffness in non-alcoholic fatty liver diseaseJournal of HepatologyVol. 56Issue 4PreviewWe appreciate the comments and clinical perspectives raised by Dr. Cross in response to our recent publication concerning the use of acoustic radiation force-based shear stiffness values in NAFLD patients to evaluate fibrosis scores [1], and we would like to take this opportunity to respond to those points. Dr. Cross mentions the significant number of failed stiffness reconstructions in our study (21.5%), which we agree would be too high for a screening test to evaluate liver fibrosis. It should be noted that the majority of those reconstruction failures (∼84%) occurred in patients with BMI >30. Full-Text PDF Open Access Palmeri and colleagues are to be congratulated on their study assessing the utility of acoustic radiation force image impulse (ARFI) to assess the severity of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) [[1]Palmeri M.L. Wang M.H. Rouze N.C. Abdelmalek M.F. Guy C.D. Moser B. et al.Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with non-alcoholic fatty liver disease.J Hepatol. 2011; 55: 666-672Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar]. However, there are several aspects from the study that need to be addressed. Firstly, the number of unsuccessful stiffness reconstructions is significant at 37/172 (21.5%). This would represent a major drawback for any screening test used to gauge the severity of underlying liver fibrosis. In addition, the area under the curve (AUC) of 0.9 for the threshold given (⩾4.24 kPa) should be re-calculated considering the frequency of the fibrosis stages and the distribution of non-advanced and advanced liver fibrosis (DANA) in the study population using the method described by Poynard and colleagues [[2]Poynard T. Halfon P. Castera L. Munteanu M. Imbert-Bismut F. Ratziu V. Standardization of ROC curve areas for diagnostic evaluation of liver fibrosis markers based on prevalences of fibrosis stages.Clin Chem. 2007; 53: 1615-1622Crossref PubMed Scopus (211) Google Scholar]. In common with all studies evaluating the accuracy of non-invasive markers using liver biopsy as the gold standard, the authors have omitted failed examinations from the final analysis. This is misleading as the accuracy and reproducibility of ARFI is then confined to successful readings and not the study population as a whole. I think all such studies should have a statistical test similar to “an intention-to-treat” analysis in clinical drug trials so that the accuracy of the study test is applied in the context of an entire study population and not only those in whom a result is achieved. Furthermore, as can be seen from Fig. 2, the shear modulus across the liver fibrosis stages is very narrow from stage 0 to stage 4. Once again, this may make interpretation of results difficult, particularly for the lesser stages i.e. stages F0–2, when clinicians may wish to identify early disease to act early to prevent disease progression. This group of patients is still likely to require a liver biopsy to differentiate non-alcoholic steatohepatitis from NAFLD, negating the prime benefit of a non-invasive test. It would be useful to assess the diagnostic accuracy of the test between different stages of fibrosis from F0 vs. F1–4 to F0123 vs. F4. One could then derive meaningful cut-offs to help guide clinical decisions based on the sensitivity, specificity, negative and positive predictive values as well as positive and negative likelihood ratios, of a respective test. The author declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.