Potential conflict of interest: Nothing to report.
Article first published online: 6 JAN 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 49, Issue 3, pages 1054–1055, March 2009
How to Cite
Vizzutti, F., Umberto Arena, Massimo Pinzani and On behalf of the other authors (2009), Reply:. Hepatology, 49: 1054–1055. doi: 10.1002/hep.22823
- Issue published online: 24 FEB 2009
- Article first published online: 6 JAN 2009
- Accepted manuscript online: 6 JAN 2009 12:00AM EST
We sincerely appreciate the debate stimulated by our article.1 As clearly stated in our manuscript1 and in replies to letters to the editor,2, 3 the aim of our study was to provide a clear cut proof of concept regarding the confounding role exerted by necroinflammation on liver stiffness measurement (LSM). Therefore, a model unequivocally characterized by acute liver necroinflammation without concomitant fibrosis was employed. It is conceivable that mechanisms other than necroinflammation could have modestly contributed to LSM values in our patients with acute hepatitis (i.e., inflammation-related edema). However, none of our acute hepatitis cases showed clear cholestatic features, and bilirubin, alkaline phosphatase, and gamma glutamyl-transpeptidase levels returned to normal or near normal values when alanine aminotransferase (ALT) activity was ≤ 2 upper limit of normal. Differently, the two cases reported by Seo and co-workers were characterized by clear signs of worsening cholestasis following an episode of acute hepatitis and should be defined as “acute cholestatic hepatitis”. This is supported by the need to perform histological assessment because of persistently high and even increasing bilirubin plasma levels in spite of aminotransferase normalization (no liver function tests and enzyme activity other than aminotransferase were reported by the authors). The possibility that cholestasis represents an additional confounding factor in LSM was already suggested by Sagir and co-workers.4 Therefore, what was presented in the letter by Seo and co-workers does not provide novelty. In any case, in a forthcoming article,5 we have highlighted the importance of future studies aimed at assessing the influence of intrahepatic and extrahepatic factors on LSM.
We are obviously aware that ALT levels are not a faithful expression of histological necroinflammatory activity, particularly in chronic hepatitis, as we have recently confirmed.6 Therefore, we completely agree that not only aminotransferase, but also other markers of necroinflammation/cholestasis must be taken in account in LSM practice, even though none of these biochemical markers directly correlate with the relative histological findings. Moreover, further elements need to be considered like passive/active congestion of the liver, distance from meals, varying results according to the site of measurement, disease etiology, body weight, etc. As an example, in a hypothetical patient with chronic hepatitis C who is taking a beta-blocker for systemic hypertension, LSM could be higher because of drug-related passive congestion of the liver, or lower due to reduced hepatic inflow. Therefore, much effort still needs to be made in order to fully elucidate the limitations of this promising diagnostic tool.
- 1Acute viral hepatitis increases liver stiffness values measured by transient elastography. HEPATOLOGY 2008; 47: 380–384., , , , , , et al.
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- 5Elastography for the non invasive assessment of liver disease: limitations and future developments. Gut. In press., , , .
- 6Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C. Gut 2008; 57: 1288–1293., , , , , , et al.
Francesco Vizzutti*, Umberto Arena*, Massimo Pinzani* , * Department of Internal Medicine, University of Florence, Florence, Italy, Center for Research, Higher Education and Transfer DENOThe, University of Florence, Florence, Italy.