Reply to: The use of acoustic radiation force-based shear stiffness in non-alcoholic fatty liver disease
Authors: Mark L. Palmeri, Manal F. Abdelmalek, Kathryn R. Nightingale
Journal: Journal of Hepatology (2011)

The use of acoustic radiation force-based shear stiffness in non-alcoholic fatty liver diseaseJournal of HepatologyVol. 56Issue 4PreviewPalmeri 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]. 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. Full-Text PDF Open AccessNoninvasive 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 We 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]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 (285) Google Scholar], 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. As discussed in the manuscript [[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 (285) Google Scholar], higher BMI is associated with deeper livers, reduced acoustic radiation force magnitudes, and therefore noisier data for performing the reconstructions. Many of these patients with failed shear wave reconstructions did not meet our quality control threshold of having an IQR/mean ⩽0.3 over the replicate shear wave estimates in the three imaging locations. This reconstruction variability is an active research efforts focused on improving the next generation of shear wave reconstruction algorithms. Additionally, we would recommend restricting the imaging locations utilized in patients with high BMI to help improve the repeatability of the reconstructed stiffnesses. While the intercostal imaging windows tended to yield repeatable shear wave reconstructions, the addition of the subcostal window was associated with additional variability in this subset of patients, most likely due to the additional subcutaneous fat at this location. Although an intention-to-treat analysis was not performed in the context of our study, one can argue that knowledge of the absence of advanced NAFLD (i.e. fibrosis stage 3–4) using a non-invasive test would decrease resource utilization and cost associated with performing liver biopsies in all patients with suspected NAFLD. As highlighted in Fig. 2 of the referenced manuscript [[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 (285) Google Scholar], the shear modulus across the early stages (fibrosis stage 0–2) of disease is very narrow, and those patients do not have increased morbidity or mortality from liver and cardiovascular related outcomes. With the exception of optimizing risk factors for disease progression, patients with early stage disease do not require surveillance and monitoring for complications associated with advanced hepatic fibrosis. We agree with Dr. Cross that additional statistical analyses are necessary to better define the sensitivity, specificity, negative and positive predictive values as well as positive and negative likelihood ratios for such a non-invasive test to have widespread clinical applicability. However, such analyses would ideally include a much larger sample size. Therefore, larger studies powered to derive meaningful threshold values capable of guiding clinical decisions are necessary. The underlying research reported in the study was funded by the National Institutes of Health.