Review for 10.1186/1471-230X-12-7 (2012)

Reviewer's report
Title:Factors Linked to Severe Thrombocytopenia During Antiviral Therapy in
Patients with Chronic Hepatitis C and Pretreatment Low Platelet Counts
Version: 1Date:7 June 2011
Reviewer: Edoardo Giovanni Giannini
Reviewer's report:
Major compulsory revisions:
1- In the Background section of the manuscript the Authors report on a previous
study referring to its results as "unpublished data". The same happens in the
Discussion section, where the Authors put in comparison their "unpublished data"
with the results published by Roomer et al. in 2010 in Journal of Hepatology. I
would suggest the Authors either to report their results or to avoid referring to
these results both in the Background and Discussion sections of the manuscript.
This is especially important as the Authors introduce the present study as a study
that stems from their previous findings (Background section, last 4 lines).
2- In the Methods section there is no explanation of how splenomegaly was
assessed. The Authors should report on ultrasound measurement and spleen
size normal data for their population.
3- I would be glad to see data reported as median and range and analysed by
using the Mann-Whitney U-test rather than the Student's t-test as I guess the
majority of data were not normally distributed.
4- Results section, lines 2-3: The Authors should report the number of patients
and not % alone.
5- Results section, lines 3-5: The Authors should provide a graph showing
platelet count behaviour (median and range with shaded areas) during antiviral
therapy. As this was one of the (main) aims of the study I feel that it is important
to provide more details regarding this point. Indeed, it may be very interesting to
see platelet count behaviour according to pre-treatment platelet count.
6- Results section, lines 7-8: Again, the rates of mild, moderate, and severe
thrombocytopenia [n and (%)] should be reported, as this too was one of the
aims of the study.
7- Results section, second page, lines 1-3: The Authors must report the n (%) of
patients who discontinued treatment due to thrombocytopenia. Furthermore, they
should analyse more in depth these two populations (patients who did or did not
discontinue treatment due to thrombocytopenia alone) in order to better
characterise these patients. Were they more frequently cirrhotics? Were they
more frequently elderly? Did they have splenomegaly? Etc.
8- Surprisingly, both the presence of cirrhosis and splenomegaly were not
associcated with the development of severe TCP during treatment. For the sake
of completeness, I would suggest the Authors to report in Table 2 even the
parameters that did not reach a p<0.1 in univariate analysis.
9- How was the platelet count cut-off of 100,000/mm3 identified. It may be
interesting to perform a ROC curve analysis in order to identify the platelet count
cut-off with the best accuracy for the development of severe thrombocytopenia
durinf antiviral therapy. Then this cut-off should be used in both univariate and
multivariate analysis.
10- How may patients had a platelet count decline different from 30% at week 2?
11- Overall, the Discussion section is too long. Some of the statements contained
in the Discussion section are not supported by evidence (first page, lines 8-11).
Furthermore, many of the speculations on platelet decline (third page,
mid-section) are not evaluable as the Authors do not report data enough on
platelet count decline during therapy.
12- Results section, last lines: many of the statements contained in these
sentences are not adequately supported by the study results.
Minor essential revisions
1- As this was a retrospective study, the term "enrolled" (Methods section,
Patients paragraph, last line) should be replaced by the term "included".
2- In the Methods section, Treatment and Follow-up paragraph, the Authors state
that treatment duration was 24 weeks for non-genotype 1 patients. Did it apply
even to genotype 4 patients?
3- Methods section, Treatment and Follow-up paragraph: Reference 10 is not
needed, as reference 11 is enough. Furthermore, reference 12 is not appropriate.
4- Table 1, Platelets line: platelet count is incorrectly reported (i.e., 12,178 rather
than 121,178).
5- Table 1: I would suggest to report n and (%) rather than viceversa.
6- Results section second page, line 6: There is no need to state "for patients
with baseline thrombocytopenia" as having TCP was the inclusion criteria and it
is supposed that all patients suffered from this condition.
7- When discussing the potential side-effects of novel drugs for TCP, the Authors
should also report that the setting where these side effects appeared was
completely different from the one assessed in the current study.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interest