Evaluation of Disease Activity in Inflammatory Bowel Disease: Diagnostic Tools in the Assessment of Histological Healing
, Otilia Gavrilescu 1,2, Mihaela Dranga 1,2,*, Iolanda Valentina Popa 2, Ioana-Ruxandra Mihai 3, Vasile-Claudiu Mihai 4, Gabriela Stefanescu 1,2, Vasile Liviu Drug 1,2, Cristina Cijevschi Prelipcean 1, Radu-Alexandru Vulpoi 2, Oana-Bogdana Barboi 1,2, Irina Ciortescu 1,2 and Catalina Mihai 1,2Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsGENERAL COMMENTS
Although the manuscript is generally well written, the article should be revised by a native English speaker.
Some paragraphs are too long (almost one page); please consider dividing them.
TITLE
OK.
ABSTRACT
Please do not abbreviate ulcerative colitis and Crohn’s disease in the abstract.
2. Histological healing - current concept and clinical relevance
Please correct/review the expression “of modern gastroenterology” (is crossed out).
3.2. Cross-sectional imaging techniques scoring systems
The information included in this section is out of the scope of the present review; please consider deleting completely this section or at least reducing it at the minimum.
4.2 Novel biomarkers predicting histological healing
This section should be more focused on histological healing, so please delete those aspects not directly related to this topic.
A section is missing in which the real applicability, in clinical practice, of the strategy of seeking histological healing is critically discussed. It is clear that IBD patients with persistent inflammation are at significantly increased risk for developing more frequent relapses; and it seems also clear that histological remission is associated with better clinical outcomes in IBD. However, it is not so clear what to do when, despite having achieved endoscopic healing, histological healing has not been achieved. Perhaps in cases treated with 5-ASA it is easy to make the decision, for example, to increase the dose, but the decision is not so clear when the patient is already receiving immunosuppressive treatment (should we escalate to biological treatment?) or when the patient is already receiving biological treatment (should we dose-intensify the treatment?). These clinical/practical aspects should be discussed.
REFERENCES
OK.
TABLES
OK.
FIGURES
OK.
Comments on the Quality of English LanguageAlthough the manuscript is generally well written, the article should be revised by a native English speaker.
Author Response
We would like to thank the Reviewer for all the positive remarks regarding our work. We are delighted to hear that the Reviewer observed the quality of the manuscript and the in-depth analysis of the subject.
We assure the EIC that we have read every suggestion from this decision letter carefully and tried our best to improve the quality of the document accordingly.
Manuscript problems are listed followed:
Q1. Although the manuscript is generally well written, the article should be revised by a native English speaker.
Answer 1.
Thank you for this suggestion.
We performed a manuscript check with the help of an English native speaker.
Q2. Some paragraphs are too long (almost one page); please consider dividing them.
Answer 2.
Thank you. The revisions are done accordingly.
Q3. Please do not abbreviate ulcerative colitis and Crohn’s disease in the abstract.
Answer 3.
Great point.
We removed the abbreviations, according to the Reviewer’s suggestion.
Q4.
- Histological healing - current concept and clinical relevance
Please correct/review the expression “of modern gastroenterology” (is crossed out).
Answer 4.
Thank you for pointing this out.
We have done the correction, as suggested.
Q5.
3.2. Cross-sectional imaging techniques scoring systems
The information included in this section is out of the scope of the present review; please consider deleting completely this section or at least reducing it at the minimum.
Answer 5.
Thank you for a very good point.
We removed the section entirely.
Q6.
4.2 Novel biomarkers predicting histological healing
This section should be more focused on histological healing, so please delete those aspects not directly related to this topic.
Answer 6.
Thank you for another good observation.
We consequently removed the information not directly related to the topic of the section.
Q7. A section is missing in which the real applicability, in clinical practice, of the strategy of seeking histological healing is critically discussed. It is clear that IBD patients with persistent inflammation are at significantly increased risk for developing more frequent relapses; and it seems also clear that histological remission is associated with better clinical outcomes in IBD. However, it is not so clear what to do when, despite having achieved endoscopic healing, histological healing has not been achieved. Perhaps in cases treated with 5-ASA it is easy to make the decision, for example, to increase the dose, but the decision is not so clear when the patient is already receiving immunosuppressive treatment (should we escalate to biological treatment?) or when the patient is already receiving biological treatment (should we dose-intensify the treatment?). These clinical/practical aspects should be discussed.
Answer 7.
Thank you for this observation.
Current guidelines do not yet consider histologic healing as a therapeutic target, as more evidence-based studies are needed. Therefore, there are currently no international guidelines in force to assist GI physicians with the specific therapeutic changes imposed by the current state of the histological disease activity.
We added a short discussion on this matter in the manuscript (Section 2), as the Reviewer suggested:
“Current drugs and their effect on intestinal inflammation struggle to achieve even endoscopic mucosal healing, which is an earlier target and usually easier to achieve than histological healing. As mentioned above, because patients with histologic persistent inflammation have a higher risk of relapse, the physician might consider optimizing any current medical therapy they are taking. For example, if a patient is taking 5-ASA agents at a low or maintenance dose but has ongoing histologic inflammation, the physician may increase that dose to try to achieve histologic healing [12]. The potency of inducing histologic remission appears to be different depending on the drug, thus, we need more evidence to demonstrate that the resolution of microscopic inflammation as a means of modifying therapy or increasing dose is indeed a superior goal [12]. Therefore, if histologic healing is taken as a treatment target, further data are needed to support and extend these findings. Current guidelines do not yet consider histologic healing as a therapeutic target, as more evidence-based studies are needed. Therefore, there are currently no international guidelines in force to assist GI physicians on the specific therapeutic changes imposed by the current state of the histological disease activity.”
Reviewer 2 Report
Comments and Suggestions for AuthorsReview article “Evaluation of disease activity in inflammatory bowel disease: diagnostic tools in the assessment of histological healing (HH)” is a well written and interesting manuscript, which systematically summarized current concept and clinical relevance of histological healing.
It adopted many important indices in ulcerative colitis as; Riley index, Geboes score, NQHA (normal or quiescent histological activity, CHA (chronic histological activity), AHA (acute histological activity), NHI (Nancy Histopathological Index), Robarts histopathological index (RHI), IBD-DCA (Inflammatory Bowel Disease-Distribution, Chronicity, Activity) score, and Harpaz score.
In histological scoring systems in Crohn’s disease, GHAS (Global Histology Activity Score) is described. And in histological scoring systems in ulcerative colitis and Crohn’s disease, IBD-DCA (Inflammatory Bowel Disease Distribution, Chronicity, Activity) score is described.
In section of cross-sectional imaging techniques scoring systems, ultrasonography, computed tomography enterography (CTE) and magnetic resonance imaging enterography (MRE) in which Magnetic Resonance Index of Activity [MaRIA] is described.
In new endoscopic tools section, confocal laser endomicroscopy (CLE), endocytoscopy (ECS), virtual electronic chromoendoscopy (VCE) and Paddington International Virtual Chromoendoscopy Score (PICaSSO) is discussed.
In surrogate markers for histological healing section, fecal immunochemical test (FIT), fecal calprotectin (FC), FC and lactoferrin (FL), Leucine-rich alpha-2 glycoprotein (LRG), Cytokine Oncostatin M (OSM), MicroRNAs (miRNAs), a combined decrease in IL-6 and IL-8 and the monitor test, also known as the mucosal healing index, including 13 serum proteins is described.
Lastly concept of “disease clearance” which was recently proposed by Danese is described.
And conclusion stated that HH is increasingly being considered an important new goal, and consequently, further histological evaluation in IBD needs to validate the role of histopathology in clinical trials and practice, mainly for patients in clinical and endoscopically apparent remission.
Author Response
We would like to thank the Reviewer for all the positive remarks regarding our work. We are delighted to hear that the Reviewer observed the quality of the manuscript and the in-depth analysis of the subject.
