JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-14-129 (2014)

Reviewer's report
Title:The Epidemiology and Treatment of Anal Fissure in a Population-based
Cohort
Version:1Date:6 June 2014
Reviewer: Giuseppe Brisinda
Reviewer's report:
I read an interesting manuscript.
I agree with the authors that the true incidence of anal fissure is not known.
The study is well conducted.
The various sections are well articulated.
The results are interesting and well explained.
Some errors are present in the tables (see nitroglycerin 2%).
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
No conflict of interest
Review for 10.1186/1471-230X-14-128 (2014)

Reviewer's report
Title:Controlling on demand gastric acidity in obese subjects: a randomized
controlled trial comparing a single dose of rabeprazole 20 mg and omeprazole 20
mg.
Version:2Date:11 February 2014
Reviewer: Manuele Furnari
Reviewer's report:
Belhocine and coworkers, conducted a well designed clinical trial on
asymptomatic and relatively healthy obese subjects to assess and compare the
response of a single oral dose of rabeprazole, omeprazole and placebo. Their
findings showed a good modification of the gastric pH by the two drugs without a
significant difference between them.
The manuscript is clear and well written in all its sections. Discussion and
conclusions are well balance.
However, due to the population setting, the results reported are poorly indicative
and applicable to the clinical practice (obese subjects, without other interacting
medications and comorbidities and especially without gastroesofageal reflux
manifestations). On the other hand, the number of subjects enrolled is low to
obtain reliable information about the pharmacodynamic. Moreover, many studies
demonstrated how the efficacy of PPIs changes even among drugs that share
the same active molecule.
Major revisions
1) Can the author provide more information (in the manuscript or as
supplementary) about the manufacturing of the medications administered to the
subjects? (It is not reported in the Trial registration, too).
2) The author found out that percent of time pH>3/24h was significantly higher on
PPI compared to placebo, but not statistically significant in terms of percent of
time pH>4/24 and median intra-gastric pH was found among the three groups.
The author should further analyse these findings in the discussion sections
(according to the secondary criteria failure of PPIs compare to placebo).
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Review for 10.1186/1471-230X-14-128 (2014)

Reviewer's report
Title:Controlling on demand gastric acidity in obese subjects: a randomized
controlled trial comparing a single dose of rabeprazole 20 mg and omeprazole 20
mg.
Version:2Date:5 March 2014
Reviewer: Fabio Pace
Reviewer's report:
The paper is interesting, well written and clear, and deserves publication.
I have no criticism at all.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests' below.
Review for 10.1186/1471-230X-14-127 (2014)

Reviewer's report
Title:Lymphomatoid granulomatosis associated with azathioprine therapy in
Crohn disease.
Version:4Date:7 May 2014
Reviewer: Sunny Hei Wong
Reviewer's report:
It is a well written case report of clinical importance and broad interest to the
readers in the field. A few points to clarify regarding the case:
Comments (major revisions)
1. The patient has Crohn's disease for 6 years. How long has she been put on
azathioprine? Has the patient received any other immunosuppressant, or biologic
therapy?
2. What serological tests for EBV were done exactly? What sample was positive
for EBV PCR / viral titre tests? Please clarify
3. Please elaborate on the pathological diagnosis of LYG. Was there any
vascular infiltration? (Reference - Colby TV, Modern Pathology
2012;25,S39–S42).
4. The authors mentioned "gastrointestinal predominant LYG" but I do not see
any evidence of luminal involvement of LYG. Was there any recent colonoscopy
finding? Was there evidence of the bowel involvement that may account for the
GI symptoms (abdominal pain and bloating)? Was there any bleeding or motility
symptom? Please elaborate
Grammar / spelling (minor revision)
Line 30: It is most often occurs (delete "is")
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-127 (2014)

Reviewer's report
Title:Lymphomatoid granulomatosis associated with azathioprine therapy in
Crohn disease.
Version:4Date:14 May 2014
Reviewer: Nagio Takigawa
Reviewer's report:
Authors described the very rare case that azathioprine therapy might induce
lymphomatoid granulomatosis.
A major point:
The relationship of liver disease (Figure 3A) with LYG in lung lesion (Figure 3C)
should be extensively discussed.
Minor points:
Line 91: Did GGT mean gamma GTP?
Line 93: After azathioprine was suspended, did Crohn disease remain stable?
Line 105: Repeat MR imaging now demonstrated extensive T1 hyperintense
lesions distributed throughout her liver, both lungs and kidneys (Figure 1).
However, in line 270, T2 weighted…
Which is right description?
Line 271, Contrast enhanced chest CT? Because the CT image was shown as
lung condition in figure 1B, please delete the words of ‘contrast enhanced’.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-126 (2014)

Reviewer's report
Title:The effect of virulence factors on the pathogenicity of Staphylococcus
epidermidis on the intestinal organs of rats and mice: an experimental
investigation
Version:2Date:20 March 2014
Reviewer: Ehinmidu O Olorunmola Joseph
Reviewer's report:
REVIEWER COMMENTS ON: THE EFFECT OF VIRULENCE FACTORS ON
THE PATHOGENICITY OF Staphylococcus epidermidis ON THE INTESTINAL
ORGANS OF RATS AND MICE:
AN EXPERIMENTAL INVESTIGATION:
1. The author’s questions are well defined.
2. Methods used are appropriate, though some methods implied used were not
reported.
i. Surrogate consent of the parents of the children whose samples were implied
used were not properly documented.
ii. The methods for isolation and standardizations of test organisms were not
stated.
iii. The state of nutrient both used to grow the test organisms were unknown.
3. The data reported are scientifically sound.
4. Relevant standards were merely acknowledged but not used.
5. The reports submitted are supported with data.
6. The limitations of the works were not well stated.
7. Reference cited were acknowledged but no 3,11,13,16,17,20 and 22 are not
conforming with standard norm adopted
8. The title and abstract do not accurately conveyed the findings of the work
done. e.g.
a. The virulence factors of the pathogenic test organisms were not lucidly
investigated to warrant the inclusion in the title.
b. The first and last sentence in the abstract has no sufficient data to sustain it
inclusion in the write.
9. The write-up as it is can not be accepted for publication because of a lot of
assumptions that have no data backup. e.g
(i) Staphylococcus epidermidis is frequently isolated species of the Coagulase
negative Staphylococci from human stool. No data was submitted to support this
claim.
(ii) The specific roles of the three virulence factors separately and collectively
were not quantitatively or qualitatively compared with known standards.
10. There are major compulsory revisions before the final decisions on this study
can be made.
Review for 10.1186/1471-230X-14-126 (2014)

Reviewer's report
Title:The pathogenicity of Staphylococcus epidermidis on the intestinal organs of
rats and mice: an experimental investigation
Version:3Date:13 May 2014
Reviewer: Atte von Wright
Reviewer's report:
2. Minor essential revisions
Despite the response of the authors, I still think that a summary table of the
histopathological results would make the manuscript more readable. If not
tabulating animal by animal, one could try the following approach:
Test group
(n = 7) Histopathological effects (No of affected animals/degree of damage)
Liver Kidney Spleen Intestine Stomach
Control 0/- 0/- 0/- 0/- 0/-
A246A x/+ y/+ z/+ v/+ w/+
A480A etc etc etc etc etc
A245A etc etc etc etc etc
The table would show the number of animals with affected organs in each
treatment group and give a qualitative indication of the degree of pathological
changes (- = no effect, + = observable effect, ++ = clear histopatholigical
damage, +++ = severe damage). Just a suggestion.
The authors should use the strain designations also in Figure legends (figures 1
-4) in the description of the treatment groups
Because the tables should be self-explanatory, the size of the treatment groups
should be indicated in Table 3.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I do not have any compteing interests
Review for 10.1186/1471-230X-14-126 (2014)

Reviewer's report
Title:The pathogenicity of Staphylococcus epidermidis on the intestinal organs of
rats and mice: an experimental investigation
Version:3Date:28 May 2014
Reviewer: Ehinmidu O Olorunmola Joseph
Reviewer's report:
The authors revision as pointed out for no 1 to 9 in the my review comments
have been satisfactorily addressed. Hence the paper can now be accepted for
publication.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interest in this article.
Review for 10.1186/1471-230X-14-125 (2014)

Reviewer's report
Title:Potentially avoidable hospitalisation for constipation in Victoria, Australia in
2010-11
Version:1Date:20 April 2014
Reviewer: KRISTINA LAMAS
Reviewer's report:
This is an interesting paper which is well written and overall well organized. I do
have some comments that the authors should consider in order to improve the
paper.
MAJOR COMPULSORY REVISIONS
Background:
Has the findings relevance from an international point of view? This could be
explained.
p3; The first section in the background, constipation is described as an adverse
effect of medications. Not mention other causes/risks make the reader believe
that the connection between constipation and medications is the main focus
further on. I should recommend to include more causes or exclude all.
p4; Poorly managed constipation is described to lead to faecal impaction which in
turn can to lead to urinary and faecal incontinence. Although constipation is
viewed as a benign condition, it brings a substantial suffering and decreased
quality of life to those affected which should be described.
Method
Cost analysis
p6; I am not sure I understand the cost analysis. I am not familiar with using
case-mixed group and perhaps misunderstand the text. However; A cost-weight
equal to 1 is a reference point based on average cost, what does it mean when
cost weight is below 1? If I understand the result right the WEIS is 0.6 for
constipation. How should I interpret that? Clarification can make this manuscript
easier to understand for reader less experienced in cost analysis.
Result
p11; Descriptions of Figure 4 in the result is not easy to follow. Some part of the
text should perhaps be placed in the method section as it describe how data
were calculated. It is written that indirect and directly standardisations were used,
what does it mean?
Discussion
The economic burden of constipation is nearly $10 million/year. To interpret the
sum it would be helpful to know the relation to total health care costs or other
known large costs in health care. When not familiar with the currency it is difficult
to understand the amount of burden, is it small or extensive?
MINOR ESSENTIAL REVISIONS
Figure 1 and 2; it says rate of separation per 1,000 population, is that right? Or
should it be 10,000?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-125 (2014)

Reviewer's report
Title:Potentially avoidable hospitalisation for constipation in Victoria, Australia in
2010-11
Version:1Date:8 May 2014
Reviewer: GEORGE PEPPAS
Reviewer's report:
I have read with great interest the article. The comments I have to make are the
following:
Tthe question posed by the authors is well defined, sound and touches an under
diagnosed condition. The methods are appropriate and well described. The data
are sound and well collected
The manuscript adhere to the relevant standards for reporting and data
deposition
The discussion and conclusions well balanced and adequately supported by the
data, there are though some points that could be made.
The problem of constipation is perfectly defined but not enough suggestions for
solving it are made. Some suggestions are:
Starting a campaign for informing both doctors and patients since both
undervalue constipation. The campaign could be digital, through the press or tv.
Therapeutic maneuvers for acute constipation i.e. high enemas, purgatives given
either at home or inhospital or OPD.
Use of laxatives.
Dietary changes, if diet poor in fiber and /or liquids
The authors clearly acknowledge any work upon which they are building.
The title and abstract accurately convey what has been found.
The writing is excellent.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-125 (2014)

Reviewer's report
Title:Potentially avoidable hospitalisation for constipation in Victoria, Australia in
2010-11
Version:1Date:13 May 2014
Reviewer: Hanne Konradsen
Reviewer's report:
This article poses an interesting and often overlooked question. It is well written
and uses appropriate methods.
I though have a few suggestions for improving the manuscript, which I consider
to be discretionary revision.
Introducing the study, the authors give a simplified presentation of conditions
relating to constipation. In example self-medication, food and liquid consumption,
psychological factors and so on might be quit important, besides possible
adverse side effect of medications.
The author uses “principle diagnosis of constipation” as a measure of the number
of patients admitted to hospital. It should be discussed though, that the number
probably is even higher. Please see Konradsen et al. Constipation – prevalence
and incidence among medical patients acutely admitted to hospital with a
medical condition, Journal of Clinical Nursing. Older patients with multiple
medical conditions might experience constipation as a contributing factor for an
unstable situation leading to hospitalization, without the condition constipation
being labelled as a principle diagnosis.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-124 (2014)

Reviewer's report
Title:Therapeutic Effect of Intensive Granulocyte and Monocyte Adsorption
Apheresis Combined with Thiopurines for Steroid- and Biologics-Naive Japanese
Patients with Early-Diagnosed Crohn's Disease
Version:1Date:18 April 2014
Reviewer: Shingo Kato
Reviewer's report:
Major Compulsory Revisions
This manuscript has new evidences of GMAA- effects on early Crohn’s diseases.
GMAA with immunomodulators(IM) has strong therapeutic effects of early
induction of remission. It’s very interesting study. However, the authors should be
clear about some questions as follows;
1. Clinical remission rate of GMAA with IM (4 weeks) was 54% in figure 1. And
also authors mentioned approximately 60% of patients will have a complete
response during the short-term outcome (30 days) of a first course of steroids in
background. I agree the early remission-induction effect of GMAA with IM was
high. However, I think direct comparison between GMAA with IM and PSL with
IM for early Crohn’s disease.GMAA therapy will be needed next. How do the
authors think about this point? Because GMAA needs high cost.
2. The authors should describe about the definition of mucosal healing.
3. How did the authors determine the total numbers of GMAA sessions for each
patient?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Review for 10.1186/1471-230X-14-124 (2014)

Reviewer's report
Title:Therapeutic Effect of Intensive Granulocyte and Monocyte Adsorption
Apheresis Combined with Thiopurines for Steroid- and Biologics-Naive Japanese
Patients with Early-Diagnosed Crohn's Disease
Version:1Date:26 April 2014
Reviewer: Piero Vernia
Reviewer's report:
The article is new and interesting, and reports for the first time in my knowledge
data on intensive GMA plus thiopurines in “early” Crohn’s disease. Results are
really interesting and prompt, as suggested by the authors, further controlled
studies.
Some issues , however, require more details.
Minor essential revisions:
- Patients should be better defined according to disease behavior ( inflammatory,
structuring, perforating CD) and presence / absence of periananal disease.
- I realize that the number of enrolled patients is small, but does this subgrouping
have effects on the response to therapy ?
- Thiopurine dosage requires more details. “Dose adjusted to < 5000 WBC” is not
enough. What was the mean daily dose? Which was the reduction in those
patients experiencing side-effects?
- “Pts responding to GMAA kept receiving thiopurines for 52 wks”.. And those
who did not?
- Mucosal heakling. It is unclear the number of patients to whom data refer both
in the results section and in Fig 2. I should anticipate that this was not evaluated
in patients with small bowel disease and in those ( how many?) in which the
terminal ileum was not evaluated .
Discretionary revisions:
- A new and interesting observation is that clinical remission was attained in 77%
of pts at week 6, and in 81-86% at week 13/26. This suggests that the further
advantage over GMA offered by thiopurines is relatively small. In my opinion this
requires some comments.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
In the last 5 years I have been lecturing for the Otsuka company in Europe.
Review for 10.1186/1471-230X-14-124 (2014)

Reviewer's report
Title:Therapeutic Effect of Intensive Granulocyte and Monocyte Adsorption
Apheresis Combined with Thiopurines for Steroid- and Biologics-Naive Japanese
Patients with Early-Diagnosed Crohn's Disease
Version:2Date:3 July 2014
Reviewer: Piero Vernia
Reviewer's report:
The authors answered to all main points raised by me as a reviewer. The article
in the revised form is now acceptable for publication without further
modifications,.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have been lecturing fot Otsuka europe in thje last years
Review for 10.1186/1471-230X-14-123 (2014)

Reviewer's report
Title:MiR-195 Affects Cell Migration and Cell Proliferation by Down-regulating
DIEXF in Hirschsprung's Disease
Version:1Date:14 December 2013
Reviewer: Alessio Pini Prato
Reviewer's report:
Methods section
1) The colonic sampling from patients with intussusception or incarcerated
nguinal hernia seemsto me definitely risky and unjustfied given the risk-benefit
ratio of this research indication.
2) Were biopsies full thickness or seromuscular? This is of utmost imortance to
understand the risk of the procedure, particularly in control subjects
Minor essential revision:
Results section:
1) Although this section is clear, I think that the Authors should provide more
information regarding patients with syndromic features (Down, syndrome, CCHS,
MW, WS4, etc) that could have a distinct genetic background.
Discretionary revisions:
1) It would be extremely interesting that the Authors try to address the possible
consequences in terms of tumor predisposition or protection of overexpression of
miR-195 as well as of the consequential down-regulation of DIEXF. In a few
words I would be interested in reading a speculative discussion with regard to the
long term consequences of these disturbed pathways in HSCR patients. In fact, a
recent paper (Oncogene 2013) demonstrated the oncosuppressor role of RET in
colorectal cancer and its relationship to tumor predisposition in HSCR patients.
What about miR-195 and other miRNAs?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-123 (2014)

Reviewer's report
Title:MiR-195 Affects Cell Migration and Cell Proliferation by Down-regulating
DIEXF in Hirschsprung's Disease
Version:1Date:12 March 2014
Reviewer: Aiwu Li
Reviewer's report:
Minor Essential Revisions
MiR-195 played a role in the pathogenesis of HSCR by down-regulated the level
of DIEXF, then a detailed function of DIEXF should be needed in this paper.
Enteric neural crest cells (ENCCs) migration disorder sometimes was related
with the abnormal extracellular matrix(EMC),so suppressing interference of EMC
is needed.
The sample size of 58 cases was not very enough for the analysis of Mi-RNA.
What the author did in this paper could not be regarded as a new pathogenesis
of HSCR, which could be regarded as a foundation for it.
Some grammatical mistakes should be modified.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests
Review for 10.1186/1471-230X-14-123 (2014)

Reviewer's report
Title:MiR-195 Affects Cell Migration and Cell Proliferation by Down-regulating
DIEXF in Hirschsprung's Disease
Version:2Date:9 June 2014
Reviewer: Alessio Pini Prato
Reviewer's report:
The authors addressed most of the concerns raised by the reviewer. However a
statement indicating that none of the patients had Syndromic HSCR should be
included in the text in order to better interprete results and conclusions.
Provided the statement is included in the text, I think that the paper is now
suitable for publication on BMC Gastroenterology.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-121 (2014)

Reviewer's report
Title:Fecal Lactoferrin in Discriminating Inflammatory Bowel Disease from
Irritable Bowel Syndrome: A Diagnostic Meta-analysis
Version:1Date:2 May 2014
Reviewer: Charles N Bernstein
Reviewer's report:
Major compulsory revisions
1.The authors do not report the actual cut off level of positive fecal lactoferrin
used. Was it the same for all studies included?
2There are 349 subjects included with UC and 365 with CD; it would still be of
interest to conduct separate analyses for UC ad CD since it would be helpful to
know if this test was useful in CD especially
3The authors do not discuss the differences between using fecal lactoferrin and
calprotectin and need to
4The English language of the paper needs to be improved
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-117 (2014)

Reviewer's report
Title:Characterization and prognosis of patients with hepatocellular carcinoma
(HCC) in the non-cirrhotic liver
Version:1Date:14 March 2014
Reviewer: Jan Best
Reviewer's report:
Schütte and coworkers performed a retrospective analysis comparing clinical and
demographic characteristics between HCC patients in a background of either
cirrhotic or non-cirrhotic liver.
Major compulsory revisions:
1) Relevant findings of this manuscript have to be discussed more thoroughly in
the context of recent literature, e.g. the progression of NAFLD to HCC in absence
of cirrhosis has prevoiusly been characterized by Ertle et al..
2) Table 5 represents treatment modalities for patients in NCL. A related table for
patients in CL background should be supplemented additionally. Maybe this will
give rise to interesting differences in applied treatment options between the two
HCC subpoulations.
3) Please provide figure legends for fig. 5 and 6
Minor Essential revisions:
1) Patient cohort determined to suffer from NAFLD has been selected by
exclusion of other causes in sonographically proven steatotic patients. It would
be desirable to have a more differential figure of the proportion of NAFLD
patients suffering simultaneously from diabetes, obesity, or more rare risk factors
such as celiac disease and additionally laboratory parameters, such as
transaminases, alkaline phosphatase,....
Discretionary Revisions:
Page 13, line 5: spelling mistake
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-117 (2014)

Reviewer's report
Title:Characterization and prognosis of patients with hepatocellular carcinoma
(HCC) in the non-cirrhotic liver
Version:1Date:17 March 2014
Reviewer: Marcus-Alexander A Wörns
Reviewer's report:
Schütte and colleagues report from a retrospective single institution experience
of a mixed cohort of patients with hepatocellular carcinoma (HCC) in non-cirrhotic
liver (NCL). They compared this entity with a large group of HCC patients with
pre-existing liver cirrhosis. They could confirm most of the characteristics of HCC
in NCL reported in the literature during the last decades. In addition, they could
demonstrate the usefulness of staging systems such as BCLC and CLIP also in
HCC patients with NLC. However, they detected a high percentage of patients
with advanced HCC (BCLC C, 51.6%) due to high rate of portal vein involvement
and extrahepatic spread (EHS). In the univariate analysis (BCLC and CLIP
excluded), portal vein thrombosis, EHS, level of AFP, PTT, ASAT, platelets, and
ECOG PS were identified as prognostic factors; in multivariate analysis, only
EHS and concentration of platelets were confirmed as independent prognostic
factors. These results highlight the implementation of surveillance programs to
detect HCC in NCL in earlier stages as the major challenge, particularly in
patients with signs of NAFLD or NASH.
Despite some limitations (retrospective study, low percentage of available
non-tumorous tissue) the results are relevant for clinical practice.
Major Compulsory Revisions:
Abstract: Conclusions have to be shortened and the main topic should be
highlighted: implementation of surveillance programs to detect HCC in NCL in
earlier stages as the major challenge, particularly in patients with signs of NAFLD
or NASH.
Results: Results of Table 6 should be included in the main text, and table 6
should be deleted. The influence of first-line treatment modalities (curative vs.
palliative approaches) should be incorporated into the univariate/multivariate
analysis. Some of the univariate analyses (Kaplan-Meier curves) should be
deleted from figure 2 and 3.
Discussion should be shortened to the most relevant points and subheadings
should be deleted.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-117 (2014)

Reviewer's report
Title:Characterization and prognosis of patients with hepatocellular carcinoma
(HCC) in the non-cirrhotic liver
Version:2Date:1 May 2014
Reviewer: Jan Best
Reviewer's report:
The main reviewers comments have been adressed by the authors sufficiently,
therefore the recent manucript version is suitable for publication.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-117 (2014)

Reviewer's report
Title:Characterization and prognosis of patients with hepatocellular carcinoma
(HCC) in the non-cirrhotic liver
Version:2Date:15 May 2014
Reviewer: Marcus-Alexander A Wörns
Reviewer's report:
All questions and comments have been sufficiently addressed by the revision
and the point-to-point response.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-118 (2014)

Reviewer's report
Title:FibroSURE as a Noninvasive Marker of Liver Fibrosis and Inflammation in
Chronic Hepatitis B
Version:2Date:23 April 2014
Reviewer: Stevan Gonzalez
Reviewer's report:
The investigators of this study evaluated the performance of FibroSURE as a
marker of fibrosis and inflammation in patients with chronic HBV. The
development of accurate noninvasive markers of hepatic fibrosis is clinically
relevant and has importance in clinical decision-making, particularly as it applies
to initiating antiviral therapy in patients with chronic HBV. Although several
studies have previously assessed noninvasive markers in HBV, the authors note
that data evaluating the role of the commercially available FibroSURE test are
limited. This is a well-written manuscript; however, there are several limitations
that should be addressed.
Major compulsory revisions:
1. How were patients selected to be included in this study? It appears that these
were not consecutive patients as the 45 individuals were selected over a long
period of time (7 years). This raises questions regarding selection bias and
should be explicitly noted in the Methods section.
2. Table 1 should provide a more complete picture of this study population,
including HBeAg status. Ranges should be given for ALT, AST, and HBV DNA
levels. An ideal HBV population in which a noninvasive test would be useful are
those with normal ALT levels – what proportion of patients had normal ALT or
less than 2x ULN ALT?
Minor essential revisions:
1. The authors do point out in the discussion that a major limitation is the small
size of this study. However an additional factor that should also be pointed out is
the heterogenous population that was included: 12/45 were co-infected with HIV
and 10/45 were on antiviral therapy with a mix of different antiviral agents. The
authors found that their cohort of HIV-positive patients were more likely to have
advanced fibrosis, be on antiviral therapy, and have elevated ALT levels.
Additionally, only a very small proportion of this study population actually had
advanced inflammation and fibrosis (n=7). This raises statistical concerns when
considering the observed trend in FibroSURE scores noted in Figures 1a/1b.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-118 (2014)

Reviewer's report
Title:FibroSURE as a Noninvasive Marker of Liver Fibrosis and Inflammation in
Chronic Hepatitis B
Version:2Date:12 May 2014
Reviewer: donald D. anthony
Reviewer's report:
This data set is a nice contribution to our understanding of the meaning of these
serum biomarker tests in the evaluation for liver damage in HBV infected
patients.
1. Abstract: the description of the patient population would be more appropriately
placed in the results instead of methods.
2. Results: it would be helpful to understand how this test performs in
HBV+HIVnegative individuals and in HIV+HBV+. The clinician will most likely
know HIV infection status prior to performing this test, and adding HIV status to
the test may not provide a clinically useful scenario. Perhaps the sample size for
HIV negative subjects is large enough to comment in this regard.
3. Discussion: it would be helpful for the reader if the authors compared
effectiveness of this test they observe in HBV infection with that previously
published during HCV infection. Is it better, worse, or the same?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-14-119 (2014)

Reviewer's report
Title:Effect of statin use on outcome of symptomatic cholelithiasis: a case-control
study
Version:3Date:22 May 2014
Reviewer: Andrea Cariati
Reviewer's report:
Ok
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have not compending interests
Review for 10.1186/1471-230X-14-119 (2014)

Reviewer's report
Title:Effect of statin use on outcome of symptomatic cholelithiasis: a case-control
study
Version:3Date:24 May 2014
Reviewer: Juan Manuel Fernández
Reviewer's report:
Minor Essential Revisions:
1) to draw conclusions from the study, an important aspect is to know the time
during which the patients had been taking statins, something that has not been
reflected in the study.
2) In table 1, Why is not calculated the P-value in the only two conditions in which
no statistical differences between the two groups (hypertension and coronary
artery disease/coronary heart failure/valvular?
3) The conclusions of the study says:" Stain treatment may also be associated
with less bleeding during laparoscopic operations" but the study has not shown
statistical significance in this aspect.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-120 (2014)

Reviewer's report
Title:Smoking, use of moist snuff and risk of celiac disease: a prospective study
Version:2Date:20 May 2014
Reviewer: Umberto Volta
Reviewer's report:
This prospective study evaluates the correlation between smoking/moist snuff
and risk of celiac disease (CD). Smoking status has been linked to several
chronic inflammatory conditions but earlier research on smoking and CD is
contradictive. The results of this research clearly demonstrate that there is no
association between smoking, moist stuff and CD development. Compared to
non-smokers, neither current smokers nor ex-smokers seem to be at increased
or decreased risk of CD.
This is a very simple paper with a well defined aim. As underlined by the same
Authors in the Discussion section, this paper has some limitations. In particular,
the Authors did not evaluate the relationship between smoking/moist stuff and
the different clinical presentations of CD (symptomatic- classical and
non-classical - and subclinical).
Major issues:
1) Background, page 4, lines 79-81: The Authors rightly point out that CD is a
multi-factorial disorder characterized by an interplay between genetics and
environmental factors. Among the environmental factors they should also
mention the role of stressful events (pregnancy, death of relatives, surgery, etc..)
in favoring the development of CD.
2) Discussion, page 15, lines 326-329. The Authors underline that villous atrophy
is rarely an expression of a disorder other than CD, reporting that in their
experience IBD is the most frequent occurrence of non-gluten related villous
atrophy. This is amazing since it is not common to find flattening of small
intestinal mucosa in IBD , whereas literature data show that villous atrophy can
be occasionally detected in other disorders such as autoimmune enteropathy,
Whipple disease, common variable immunodeficiency, giardiasis and cow-milk
protein intolerance. Therefore, the Authors should add a sentence illustrating the
possible finding of villous atrophy in the above mentioned conditions (add one or
two references).
Minor issue:
1) Conclusions, page 17, line 359: “This prospective In conclusion, we found ….”
the sentence should be completed or amended.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-120 (2014)

Reviewer's report
Title:Smoking, use of moist snuff and risk of celiac disease: a prospective study
Version:2Date:2 June 2014
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
Ludvigsson et al. examine the association between smoking, moist snuff and risk
of celiac disease in a Swedish cohort. Overall, this is a well done study using a
power database and the manuscript is written well and the methods adequately
explained.
Some of my concerns which I think need to be addressed are listed below. I think
these can be quite easily addressed within the context of this manuscript and
would improve the utility.
Major Concerns:
1. Since this was a study from blue collar and white collar workers, it is possible
that there is a healthy worker effect in that patients with significant celiac disease
are excluded from these occupations? Please discuss if this is possible and if it
would influence the results.
2. The post hoc analysis showing a significant protective effect in women but not
men is quite striking. This is mentioned for the first time in the discussion but I
think should be mentioned in both the methods and results. Please discuss
potential explanations for this. I think this is the most interesting finding of this
study and merits some discussion.
3. The prior study by the authors (CGH 2005) included only women and showed
no association with smoking. This is in contrast to the findings during the present
study. Please explain the potential reasons for this discrepant result.
Minor points:
1. In their Methods (Page 6) – the authors report that the quality of smoking data
has been previously reviewed and is high. Since that is the primary predictor of
this manuscript, I would suggest provided a little more detail on that. How was
the accuracy confirmed, and please quantify the accuracy rather than merely
citing the previous publication.
2. Page 8 – the meaning of the first sentence is not clear. It says 29,146
individuals formed the basis of this study – but the numbers listed for smoking
and snuff are much higher. Please clarify.
3. For the power calculation – Page 8. I appreciate the authors providing this
information. Please clarify baseline prevalence of celiac disease used to arrive at
the power estimates.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests.
Review for 10.1186/1471-230X-14-120 (2014)

Reviewer's report
Title:Smoking, use of moist snuff and risk of celiac disease: a prospective study
Version:3Date:24 June 2014
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
My questions have been addressed and I find the paper acceptable for
publication
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests.
Review for 10.1186/1471-230X-14-116 (2014)

Reviewer's report
Title:Clinical characteristics of elderly patients with proton pump
inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who
responded to rikkunshito
Version:2Date:3 May 2014
Reviewer: Toshimi Chiba
Reviewer's report:
1) General comments
Sakata et al. described Clinical characteristics of elderly patients with proton
pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who
responded to rikkunshito. The article is informative and well-presented. The
reviewer has some comments.
Comments
1. In page 6, line 136, ‘Full inclusion and exclusion criteria have been previously
presented [16]’, the Ref. No. 16 has not been printed yet. We cannot confirm
these criteria right now. Please describe these criteria in detail in this paper.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Review for 10.1186/1471-230X-14-116 (2014)

Reviewer's report
Title:Clinical characteristics of elderly patients with proton pump
inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who
responded to rikkunshito
Version:2Date:6 May 2014
Reviewer: Kunihiko Aoyagi
Reviewer's report:
The previous G-PRIDE study showed that rikkunshito (RKT) may be useful for
improving mental quality of life and dyspeptic symptoms in patients with
PPI-refractory NERD, particularly for elderly and female patients (J Gastroenterol
2014). To evaluate clinical characteristics of elderly PPI-refractory NERD patients
with ARD symptoms who responded to RKT (RKT), in the present study, the
authors analyzed elderly patients with 1 or more FSSG out of the previous
G-PRIDE study. Combination therapy with RKT (RKT group) for 8 weeks showed
significant improvement in 3 subscale scores (abdominal bloating, heavy feeling
in stomach after meals, and sick feeling after meals) of the ARD domain and 1
subscale score (heartburn after meals) of the reflux symptom domain. From
these data, they concluded that RKT was particularly effective for resolving
postprandial GERD symptoms (heavy feeling in stomach after meals, sick feeling
after meals, and heartburn after meals) in elderly PPI-refractory NERD patients
with ARD.
Major
However, it is well known that the symptoms of postprandial distress syndrome
and epigastric pain syndrome, the two subtypes of functional dyspepsia under
the new Rome III classification, tend to overlap with those of NERD (Shindo T,
Digestion. 2009;79:65-72).
Although dyspeptic and IBS-like complaints overlap with GERD symptoms as
mentioned in the discussion, it seems difficult whether patients in this study are
diagnosed as having PPI-refractory NERD or functional dyspepsia. Is this cohort
appropriate for the trial that characterize the elderly PPI-refractory NERD patients
who respond to RKT?
To clarify clinical characteristics of elderly PPI-refractory NERD patients who
responded to RKT, the authors should demonstrate the differences in clinical
characteristics between the RKT responsive group and nonresponsive group. In
this respect, this manuscript has insufficient data to achieve the aims.
Minor
Exactly the same sentences in the discussion are seen as in the previous similar
study (J Gastroenterol 2014).
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.