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Please address the basic reporting changes requested by Reviewer #2.
1. Well-structured and well written manuscript with clear and professional English language.
2. Professional and well conducted tables and figures.
3. Clearly explained introduction explaining the clinical importance of the topic.
1. Well defined and relevant research question with very limited published research on the topic.
2. Clearly described methods that allow it to be reproducible by other researchers.
1. This study evaluates the association between NAFLD and nonspecific ST-T segment changes with the largest study sample which adds to the current literature.
2. Multivariable logistic regression analysis was performed to evaluate for confounding factors.
3. Conclusions can't confirm causality (as mentioned by the authors). Nevertheless, the reported conclusions were based on the demonstrated results.
The authors modified the manuscript as per the previously mentioned suggestions. This is a well conducted cross-sectional study that adds new insights to the scientific literature. I believe that the manuscript can now be considered for publication.
The article is well written in professional English, there are only few things I would change:
- Line 200: the present study (not studies) provided evidence;
- Line 205: I would change the phrase “the population we surveyed was relative health patients“ with “the population we studied was made up of relatively healthy people”
Introduction and background are well written; literature is well referenced and relevant.
Relevant figure, adequate and well labelled
Raw data: satisfactory
As I stated on the previous review I think this is an original primary research. On Medline several correlations are described between NAFDL and cardio-vascular disease, but none specifically with NST changes.
I think this research fills a knowledge gap.
The investigation is rigorous; the methods are described in detail
Data are provided and look statistically sound
Speculation is identified as such.
Conclusions are well stated.
Researchers encourage further studies on the subject.
I do appreciate the changes that have been made, which in my opinion make the article more complete. I do appreciate the clarification on the approval to the study given by the ethics committee (and the file provided).
I think the article is well written and it is an original research.
Your paper was reviewed by 2 independent experts in this field and there are several revisions which will be needed. The Reviewers have raised several issues related to the Basic Reporting, Experimental Design and Validity of the findings which should be thoroughly addressed in any subsequent revisions including clearly acknowledging and delineating any additional Limitations. Please also address each of the enumerated “Comments to authors” in your revision.
[# PeerJ Staff Note: Please ensure that all review comments are addressed in a rebuttal letter and any edits or clarifications mentioned in the letter are inserted into the revised manuscript where appropriate.
It is a common mistake to address reviewer questions in the rebuttal letter but not in the revised manuscript. If a reviewer raised a question then your readers will probably have the same question so you should ensure that the manuscript can stand alone.
Directions on how to prepare a rebuttal letter can be found at: https://peerj.com/benefits/academic-rebuttal-letters/ #]
1. Well-structured and well written manuscript with clear and professional English language.
2. Professional and well conducted tables and figures.
3. Clearly explained introduction explaining the clinical importance of the topic.
1. Well defined and relevant research question with very limited published research on the topic.
2. Clearly described methods that allow it to be reproducible by other researchers.
1. Although this isn't the first study to evaluate the association between NAFLD and nonspecific ST-T segment changes, it is the largest in population size which adds to the current literature.
2. Multivariable logistic regression analysis was performed to evaluate for confounding factors.
3. Conclusions can't confirm causality (as mentioned by the authors). Nevertheless, the reported conclusions were based on the demonstrated results.
- Main theme of the manuscript:
This is a retrospective cross-sectional study conducted on 32,922 participants who presented in a single hospital (Wuhan Union Hospital), aged between 18 to 65 years. The aim of the study was to assess the association between NAFLD and nonspecific ST-T segment changes on ECG. The authors demonstrated that subjects with NAFLD are independently associated with an increased incidence of ST-T segment changes on ECG, even after adjusting for potential confounders.
- Current literature:
The current literature is limited in data evaluating the association between NAFLD and non-specific ST-T segment changes on ECG. Two studies and a systematic review evaluated this association. A cross-sectional study conducted on Korean adult subjects by Lee et al. involving 50 NAFLD patients and 100 age and gender matched controls demonstrated that ischemic heart disease changes on ECG weren’t independently associated with hepatic steatosis. On the other hand, Vendhan et al. conducted a cross-sectional study on 541 participants demonstrating a significant association between nonobese NAFLD and coronary artery disease defined by ECG changes including ST-segment depression, Q-wave changes, or T-wave changes associated with ischemic heart disease, even after performing multiple logistic regression analysis. Moreover, a recently published systematic review conducted by Ismaiel et al. evaluated the methodological quality of the previously mentioned studies and rated the first mentioned study (Lee et al.) as “fair” and the second (Vendhan et al.) as “good”, supporting the presence of ECG changes related to ischemic heart disease in NAFLD.
- What’s new?
The current study is of interest in the fields of gastroenterology, cardiology as well as internal medicine as NAFLD is a multisystem disease with a rapid increase in prevalence worldwide. Cardiovascular risk stratification in NAFLD patients using an ECG, a simple and widely used device, is of great clinical significance. The authors conducted a study with the largest study population at the moment assessing nonspecific ST-T segment changes in NAFLD allowing a better evaluation of this association on a large number of subjects. Demonstrating an increased incidence of ST-T segment changes in NAFLD patients, even after adjusting for confounders on such study population adds to the current literature as results can be generalized to a larger extent.
- Comments:
1. Please mention the period of recruitment in which the subjects were reviewed at the physical examination centre in Wuhan Union.
2. Please describe the characteristics of study participants (eg demographic, clinical, social).
3. You mentioned that patients with missing liver function tests were excluded from the study. I couldn’t find AST, ALT, GGT and ALP levels? Were they assessed in the included study participants?
4. In the current study, hepatic steatosis severity evaluated using abdominal ultrasonography was classified into normal, mild, or moderate/severe although the ultrasonographic severity classification of hepatic steatosis is divided in to grades 0-4 (grade 0, absent; grade 1, mild; grade 2, moderate; grade 3, severe). Why did you combine moderate and severe together in the same severity grade?
5. The discussion section didn’t discuss the current results of the published studies evaluating nonspecific ST-T segment changes in NAFLD. Please have a look at the currently published studies evaluating this association and discuss how your results are similar/different. Below are some studies evaluating this association.
• Study 1 (2006):
(https://www.tandfonline.com/doi/full/10.1080/00365520500319591?scroll=top&needAccess=true)
• Study 2 (2014):
(https://www.liebertpub.com/doi/10.1089/dia.2013.0165)
• Systematic review (2019):
(https://www.jgld.ro/jgld/index.php/jgld/article/view/344/168)
6. How would you explain that patients with mild hepatic steatosis have an increased incidence of nonspecific ST-T segment changes compared to patients with moderate/severe steatosis? You can discuss this in the discussion section.
7. The word “Notably” in the second line of the discussion section should have the letter n in lowercase.
8. Use of the abbreviation “NAFLD” isn’t consistent throughout the manuscript. Some sentences have the abbreviation while others have the full word mentioned (nonalcoholic fatty liver disease). Please mention the full word with the abbreviation on the first appearance in the manuscript and then use the abbreviation only.
- Limitations:
1. Diagnosing NAFLD using abdominal ultrasonography might underestimate the prevalence of NAFLD.
2. The retrospective cross-sectional study design doesn’t allow the demonstration of causality between NAFLD and nonspecific ST-T segment changes in NAFLD.
3. Residual confounders were not excluded due to the measurement errors of these variables.
- Strengths:
1. Well-structured and well written manuscript with clear and professional English language.
2. Professional and well conducted tables and figures.
3. Limited literature published on this topic (2 cross-sectional studies and 1 systematic review published on PubMed) making it of significant clinical importance due to the associated cardiovascular risk.
4. Good methodological quality evaluated using STROBE quality assessment tool for cross-sectional studies.
5. Large sample size.
- Summary:
I believe that this is a well conducted cross-sectional study that could be considered for publication after performing the above-mentioned modifications that will improve the quality of the manuscript.
The article is well written in professional English.
There are only few parts I would modify:
- I would replace the word ‘coincidentally’ in line 50 with a more straightforward word;
- I would change the word “obese” in line 141 with “heavier” (or similar), seen that the average BMI was way inferior to 30;
- In lines 149 and 152 the phrase “the proportion of NST changes” could be misleading; I would change it with “the proportion of patients with NST changes”;
- I would integrate the phrase in line 139-140 as it follows: “a higher prevalence presented in middle-aged and older individuals (third and fourth quartile of age)”. I think it gives a better link to your study’s population.
I think that the introduction needs more details. I personally would add some more background information about NAFLD in lines 49-50 (see Targher G et al. NEJM, 2010).
The structure is conform to PeerJ standards.
Figures are relevant and of high quality.
In Table 2, line 4 I would change the word “unadjustment” with “unadjusted”
Raw data are supplied and are satisfactory.
This is an original primary research. There is no such a research in literature yet. On Medline we can find correlations between NAFDL and QTc prolongation, PR prolongation, presence of AF, ventricular arrhythmias, RBBB, but none with non specific ST-T segment changes.
This is the reason why I think the research fills an identified knowledge gap
The investigation is rigorous. I think there may have been a mistake about the numbers of the participants included in the final analysis (32922 as shown in the fig. 1 vs 32864 as described in line 91?). The raw data show 32922 participants.
Methods are described in detail.
I do appreciate that researchers encourage further studies on the subject
All the data are provided and look statistically sound
Speculation should be identified as such: in line 180 I would change the verb “indicate” with the verb “suggested”, only to underline once more that correlation is not causation
Conclusions are well stated
I think the article is well written and it is an original research.
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