To the Editor:
We read with interest the paper by Mehta et al. [
[1]
] that reported that due to imperfection of liver biopsy as a reference standard it is not possible to estimate the accuracy of a non-invasive test for the diagnosis of liver fibrosis. However, we would like to challenge some points raised.Diagnosis cannot be regarded as a primary outcome but alternatively can be represented as a decisional node.
The identification and staging of a disease (diagnosis) should support the decision to treat a patient or not. The utility of diagnosis derives from the benefits of this decision. Thus, in the context of liver disease, patients with severe fibrosis have a worse prognosis and those with significant fibrosis fare better with treatment. The identification of these subgroups is useful and allows the definition of their prognosis and initiation of effective treatment, but these differences in prognosis and benefits of treatment have widely been evaluated using exclusively histological definition, even if imperfect. Actually, no diagnostic test can be regarded as perfect and thus there are no longer “gold” but only reference standards. The limitations of liver biopsy are well known; the most important being the high percentage of false-negative results yielded in the cases of significant or severe fibrosis.
In the study by Mehta et al. there is an implicit assumption that the prognosis and the response to treatment in patients with false-negative results at histology are actually the same as in those with true-positive results. This assumption has still to be unequivocally proved. So far, it has not been possible to assume that non-invasive fibromarkers are more useful only for the merit of reducing the false- negative rate of histology. In fact, only the assessment of the prognosis of patients with discrepant results (between histology and fibromarkers) could define their actual advantage.
An unequivocal demonstration would entail a randomized controlled trial comparing hard clinical outcomes in patients in which the diagnosis of significant or severe fibrosis was obtained either by histology or by non-invasive fibromarkers.
Furthermore, the analysis by Mehta et al. is limited to the overall accuracy and AUC assessment: these are two diagnostic measures of true results, but no information can be derived on false-positive or -negative results. However, the clinical utility of a diagnostic test depends on false-negative and positive rate (i.e. on sensitivity and specificity).
Finally, Mehta et al. [
[1]
] seem to conceive possible alternatives to liver biopsy only in the form of a single test. In our opinion, the choice of a diagnostic strategy comprising sequential tests (conditionally independent) [2
, 3
] with different operative characteristics may be more effective. For the diagnosis of fibrosis, a diagnostic flow chart can be designed using an initial highly sensitive test to rule out the diagnosis if negative and if positive followed by more specific tests to confirm it.References
- Exceeding the limits of liver histology markers.J Hepatol. 2009; 50: 36-41
- Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C.J Hepatol. 2006; 44: 686-693
- A non-invasive algorithm accurately predicts advanced fibrosis in hepatitis C: a comparison using histology with internal-external validation.J Hepatol. 2008; 49: 564-571
Article info
Publication history
Published online: January 09, 2009
Identification
Copyright
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc.
User license
Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) | How you can reuse 
Elsevier's open access license policy
Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Permitted
For non-commercial purposes:
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article (private use only, not for distribution)
- Reuse portions or extracts from the article in other works
Not Permitted
- Sell or re-use for commercial purposes
- Distribute translations or adaptations of the article
Elsevier's open access license policy
