Review for 10.1186/1471-230X-11-91 (2011)

Reviewer's report
Title:Non-Invasive Biomarkers for Hepatic Fibrosis
Version: 1Date:8 April 2011
Reviewer: Tim Cross
Reviewer's report:
A considerable amount of work has gone into the review on biomarkers for
hepatic fibrosis. The authors describe the biology of liver fibrosis and the different
types/classification of hepatic fibrosis. The authors then go on to describe the
different mechanisms involved in the different acquired forms of hepatic fibrosis.
They then describe the different histopathological scoring systems that are
applied to hepatic fibrosis and also to hepatic steatosis. The final section of the
review outlines transient elastography and MRI elastography and then describes
individual biomarkers and their accuracy in determining different stages of
hepatic fibrosis.
The manuscript could be improved in the following ways:
1. At present the manuscript is too long. The article is written in a dry style and is
quite difficult to read. The author appears to be attempting to get all aspects of
hepatic fibrosis into one clinical review. If the review were more targeted and
digestible that would help. Is the article about fibrogenesis and its mechanisms,
different classification or is it about the clinical application of non-invasive
markers in everyday practice? That should be the starting point. Mentioning
everything means that the article appears to have no focus or direction. It may
have been possible to tie some of these strands together by incorporating factors
contributing to fibrosis in various disease etiologies and then describing a host of
biomarkers for that disease ( a template for this could be the review by Martinez
SM, et al Hepatology 2011;53:325-335).
2. If the focus is on the clinical application of these tests one should mention the
importance of frequency of fibrosis stage on AUROC curves (Poynard et al,
Clinical Chemistry 2007). It is this that may account for the different AUROCs
observed in different study populations. I also felt that the section on transient
elastography could have been expanded to discuss its utility in a number of
clinical conditions e.g. HCV, HBV, alcohol, NAFLD etc.
3. A table outlining the pros and cons of imaging techniques versus the different
direct/indirect markers of fibrosis may be a useful summary. In particular factors
that may influence the respective results e.g. inflammation, haemolysis, obesity,
reproducibility, complexity of calculations, speed with which results are available
to clinician etc.
4. The authors offered no suggestion as to how they believed that tests should
be applied. A proposed algorithm for the use of non-invasive tests and the
circumstances in which liver biopsy still might be utilised may be a helpful figure.
5. By the same token a more critical appraisal of each biomarker/panel/imaging
technique would improve the review. What’s good and what’s the bad about the
tests, when would it be useful, how should it be applied, in what conditions may
the readings lead to false negatives/positives etc. Figures and studies are
reproduced but this latter section requires more interpretation.
Minor corrections:
The calculation for APRI is incorrect. It should be (AST/upper limit of normal for
AST)/platelet count x 100.
In the conclusion the authors say that many of the tests are not widely validated.
I think proponents of Fibrotest, ELF and transient elastography may argue with
that assertion.