Reply:
Authors: Francesco Vizzutti, Umberto Arena, Massimo Pinzani
Journal: Hepatology (2008)

We appreciate the comments by Panos and colleagues and the editorial by Cobbold et al.1 We also read with great interest the paper by Sagir et al.2 reporting findings in agreement with to those of our study.3 Our study was specifically designed to definitively evaluate the possible interfering role of necroinflammation on transient elastography (TE) measurement. Accordingly, we investigated a cohort of patients with acute viral hepatitis. The conclusions arising from our study were that necroinflammation, in the absence of concomitant fibrosis, significantly influences TE results (that is, overestimation); TE is unsuitable to detect an underlying chronic liver disease during acute liver damage. Therefore, we can assume, also on the basis of previously published data,4, 5 that necroinflammation could influence TE measurement in patients with chronic liver disease. As a result, in clinical practice the degree of necroinflammation may limit the diagnostic accuracy of TE, especially in patients with lower-intermediate stages of fibrosis. This may account, at least in part, for the overlap commonly observed by using TE in the prediction of lowest and intermediate stages of fibrosis, and the variability in TE cut-off values for the prediction of different fibrosis stages proposed by different authors (for a review, see Pinzani et al.6). Therefore, from a practical point of view, it seems reasonable to consider cautiously TE values obtained in patients with unstable biochemical activity. However, this precaution cannot prevent the overestimation of TE values due to necroinflammation. Indeed, it is well established that the degree of necroinflammation determined by histologic analysis and by analysis of biochemical activity are not necessarily correlated. We have some difficulties in understanding the contribution of TE in the clinical assessment of acute liver damage proposed by Panos et al., and especially its clinical usefulness, in terms of diagnosis and prognosis, in respect to the standard clinical assessment. In particular, two suggestions of these authors—namely, the use of TE for detecting the worsening of acute hepatitis and its possible evolution toward a fulminant form and for perceiving the presence of a "dual infection" hepatopathy—are at present merely hypothetical and need to be adequately substantiated. We agree that TE could be employed for monitoring disease recurrence in orthotopic liver transplantation patients. However, this methodology needs to be further evaluated in the clinical setting before being suggested as a reliable diagnostic tool. Indeed, results obtained in patients who have not undergone transplantation are not directly transferable to patients who have undergone transplantation, who show a different pattern of fibrotic evolution and a possible concomitant graft damage due to chronic rejection. Finally, we agree with Panos and colleagues that TE represents an exciting area of research and a potential source of innovation for the clinical practice of hepatology. Ideally, efforts should be directed at clarifying the presence and role of additional interfering or confounding factors. In this contention, the impact of cholestasis on liver stiffness (in part suggested by the data by Sagir et al.2) certainly deserves further investigation. Eventually, integration of TE with other noninvasive measures of disease progression will likely lead to a more comprehensive clinical assessment of patients with chronic liver disease. Francesco Vizzutti M.D., Ph.D.*, Umberto Arena M.D.*, Massimo Pinzani M.D., Ph.D.* , * Dipartimento di Medicina Interna, Università degli Studi di Firenze/Azienda Ospedaliero Universitaria Careggi Firenze (AOUC), Florence, Italy, Center for Research, Higher Education and Transfer (DENOThe), Università degli Studi di Firenze/Azienda Ospedaliero Universitaria Careggi Firenze (AOUC), Florence, Italy.