Review for 10.1186/s12876-016-0492-6 (2016)

Reviewer ’s report  
Title:  Peripheral blood toll -like receptor 4 correlates with rapid virological response to 
Pegylatedinterferon and ribavirin therapy in hepatitis C genotype 1 patients  
 
Version:  0 Date: 17 Jan 2016  
 
Reviewer:  Vincenzo  Palmieri  
 
Reviewer's report:  
Main finding of this work is that mRNA expression of TLR 2, 3, 4, 7, and 9 was lower in the 
RVR group, compared with the non -RVR group. This indicates that TLR (TLR4 in particolar) 
may play  a crucial role in HCV recognition and activation.  
Bu the authors do not explain why the relation between mRNA expression of these receptors and 
the SVR (that represents the real therapeuic aim of the PG -IFN/RBV therapy) is absent.  
They do not spend any wo rd in the discussion in order to explain this great limit of the study.  
Moreover, they correctly mention the work of He et al (Liver International 2006), that has some 
methodological overlapping with this work, but in which the levels of expression of TLRs  
receptors are evacuate in relation to the SVR and not to the RVR.  He et al. that baseline PBMC 
TLR 2 and 3 mRNA levels were significantly higher in patients with SVR than in non -
responders, a result that is opposite to that reported by the authors of the  proposed paper in this 
review. Even if in the paper of Liver International the number of patients is low, the authors need 
to analyze with more details the reasons of this so clear discrepant conclusion. This topic is 
absolutely relevant and I wish to men tion a "small" but more recent paper published in chinese 
language (so I could have access only to the abstract) (see complete enclosed reference): the 
authors show that surface expression of PD -1, TLR4, and PD -1:TLR4 is up -regulated in the total 
PBMCs of CHC patients and that Peg -IFNalpha -2a plus RBV treatment -induced suppression of 
HCV replication results in a significant reduction in PD -1 and TLR4 expression on the surface of 
PBMCs. This data seems to confirm the results of the work of He et al, but not with that of the 
paper we are reviewing.  
The auhors, therefore, need to explain:  
- the reasons why the relation of mRNA expressione of TLRs with the RVR is lost when the 
SVR is taken into account  
- the reasons why their resuls is in contrast with the twuo previous work that I have mentioned  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
No 
Are you able to assess any statist ics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaration of competing interests  
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