Review for 10.1186/1471-230X-14-113 (2014)

Reviewer's report
Title:Association of MRC-1 and IL-28B with the treatment outcome of hepatitis
C: a case control study
Version: 1Date:9 July 2013
Reviewer: Faisal M Sanai
Reviewer's report:
Comments
major
1. RVR has been shown to be perhaps the most predictive factor for SVR is HCV
patients receiving antiviral therapy. I fail to understand why the impact of various
factors towards RVR is being studied here. Certainly it fails to serve any purpose
towards studying predictors of RVR and SVR in the same study, where one
factor is actually predictive of the other. The study would be clearly better, and
adequately shortened, by studying only SVR. In this, RVR should be studied as a
predictor of SVR. This would eliminate many of the tables and vast parts of the
results section. In my opinion, this would render the article more readable and
easier to follow.
2. I would recommend that the article deal with either one of the HCV genotypes
(1 or 2) and not both of them together in one manuscript. If the authors wish to
combine both genotype results in this study, then perhaps the viral genotype
could be studied as a predictive factor, rather than describing the SVR results of
both genotypes separately and studying their predictive factors separately as
well.
3. The method of multivariate analysis performed is not entirely clear. Did the
authors put all clinical, virological and host genotypic factors that were significant
at the univariate level in to the multivariate level? This aspect should be clarified.
All factors that were significant at the univariate level for SVR should be put in
the multivariate model.
4. Table S1 should not be a supplementary table. It should be placed as a main
table since it is the most relevant question being addressed in this study.
5. The statement ‘all SNP in IL28B were genotyped’ is incorrect. There are many
other SNP’s in the IL28B region and these have been conspicuously overlooked.
In fact the authors have failed to test the most commonly associated SNP of
IL28B gene which has been associated with SVR, which is the rs12979860.
Despite the rare study that has shown rs8099917 and rs8105790, amongst
others, as predictive of SVR, the authors should have tested for the commoner
and more predictive SNPs. This limitation should be discussed by the authors.
6. In the conclusion of the Discussion, the authors state ‘In Taiwan, HCV-1 and
HCV-2 patients carrying IL28B and MRC-1 low-response alleles and genotypes
could potentially be given longer antiviral treatments.’ This appears like a
conclusion, which is totally unsupported by the study findings. The authors could
certainly discuss the implications of their findings but this ought to be done in the
correct context. This aspect could be discussed separately from the conclusion.
This will enhance the Discussion section as it presently simply presents the
results, without adequately discussing the pros and cons and the implications.
The present condition of the Discussion section is rather redundant, wherein
large segments of it could easily be removed without loss of intellectual value.
7. Table 1 and 2 are too long and one loses track of its content and significance.
If the authors are to accommodate my earlier recommendation of studying just
the SVR and one genotype then aspect would be addressed. Further, it should
be simplified, preferably by breaking it up in to two separate figures (for IL28B
and MRC-1; where each SNP could be represented within a constellation of
figures).
Minor
1. Were all patients treatment-naïve? What was the definition of high viral load?
The authors have categorized patients in to low/high (table 5) without telling the
readers what was the cutoff point. The definition should be mentioned in the
results section and not just in the footnote of the table.
2. There is a conflict in the HCV RNA units being reported – where the assay is
mentioned, it states IU/mL while the authors state that values were reported in
copies/mL. Which is correct?
3. The description of RVR +/- and SVR +/- is redundant. Most readers generally
understand (or will understand from your subsequent circumscribed description)
what is RVR and SVR. There is no need to describe what is NOT RVR and SVR.
4. In the results, about 41% and 62.5% of the HCV-1 patients achieved RVR and
SVR, respectively. This, in my opinion is a rather high number. How do the
authors explain this?
5. The description of the univariate analysis for RVR and SVR is rather laborious
and could be mentioned in one or two sentences, with a reference to the table.
The present description is merely a duplication of what is already depicted in the
table.
6. I could not understand this statement, or what exactly the authors intend to say
“However, we can still detect a high frequency of the T allele in patients with SVR
(72.3% in this study).
7. The English language could definitely be improved (particularly in the Results
section) by seeking professional help.
8.