Steatosis and liver stiffness measurements using transient elastography
Authors: Peter Eddowes, Magali Sasso, Celine Fournier, Raj Vuppalanchi, Philip Newsome
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Fournier is employed by Echosens. Dr. Sasso is employed by Echosens. Grant support: P.N.N./P.E. are supported by the NIHR Birmingham Liver Biomedical Research Unit based at University Hospitals Birmingham and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. TO THE EDITOR: We read with interest the article by Petta and colleagues.1 The potential impact of hepatic steatosis on the interpretation of transient elastography findings is an important clinical issue, and we congratulate Petta and colleagues for performing this analysis in a large cohort of nonalcoholic fatty liver disease (NAFLD) patients. However, there are certain aspects of this study that merit further consideration. Firstly, all the patients in the study cohort had transient elastography performed using the M probe, despite an elevated body mass index (29.1 ± 4.2 kg/m2). Such patients are likely to have a skin to capsule distance >25 mm, which could result in an overestimation of their liver stiffness measurement (LSM) with the M probe.2 This limitation should be acknowledged and consideration given to including assessment of skin to capsule distance as a potential confounding factor in this study. Secondly, there are significant histologic differences between NAFLD patients with and without severe steatosis (>66%). Patients with F0/F1 fibrosis were pooled together, but for patients with severe steatosis 60% were F1 compared to 53% of those without severe steatosis. Similarly, the distribution of fibrosis in patients with severe steatosis is skewed toward greater levels of fibrosis than those without severe steatosis (43% F2, 34% F1, and 22% F0 versus 25% F2, 40% F1, and 35% F0). Thus, higher LSM in the severe steatosis group may very well reflect subtle but significant differences in the distribution of fibrosis. Thirdly, the authors in their Materials and Methods indicate that multivariate analysis is performed "including all the significant baseline variables (P < 0.05)," yet in their Results two parameters that were not significantly linked to LSM in the univariate analysis (liver biopsy length and LSM interquartile range/median) were included in the multivariate model. In contrast, fibrosis stage, which is known to be linked to LSM, was not included in the model. In NAFLD, histological features such as steatosis, inflammation, ballooning, and fibrosis are closely linked; and thus, all these parameters should be entered into the multivariate model because they could be potential confounding factors. Thus, it would be important to establish whether the relationship between LSM and steatosis remains when adjusted for histological features, particularly fibrosis stage. Nonetheless, this is an important issue; and thus, prospective studies are under way (NCT01985009) using the M and XL probes in obese patients with NAFLD together with controlled attenuation parameter analysis that would allow for simultaneous assessment of hepatic steatosis.