Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature

Round 1

Reviewer 1 Report

The authors give an update of HILI, including herbal dietary supplements (HDS). The literature search is extensive and covers all relevant databases. The description of cases and articles is to-the-point. HILI biomarkers and herbal hepatoprotective agents are briefly discussed. Relevant scoring systems are mentioned and used. Possible treatment of HILI is discussed. Obviously, there is a lack of randomised trials, and even a lack of large cohorts. The difficulties in delineating pathophysiology are mentioned. The manuscript is clearly written.

Author Response

Thank you very much for taking the time to review our manuscript.  We appreciate your kind comments and we hope this review will provide readers with detailed as well as relevant information to further their knowledge base and clinical practice. We have edited our draft to improve grammar and sentence structure as well as reviewed our references. Thank you again for your time. 

Reviewer 2 Report

In this review, Patel-Rodrigues and colleagues analyze recent literature in relation to liver damage induced by the use of herbs, mainly taken as dietary supplements. The authors point out that the diagnosis of HILI (herbal induced liver injury) is challenging and difficult to diagnose, especially in the absence of specific analyzes and requiring a careful analysis of the symptoms presented by patients and excluding other possible causes of liver damage.

They continue describing the current laws and regulations related to herbal supplements highlighting the lack of regulation related to (most of) these products as well as the guidelines on the diagnosis and the management of HILI globally.

One of the important points is the fact that culture and tradition have a huge impact from this point of view, finally describing a series of herbs normally taken and (possibly) associated with liver damage.

The paper is well structured and written, and provides a lot of information as well as several points for reflection regarding this topic.

It would be interesting if a further division were made between the herbs taken regularly with the diet, and therefore practically daily, from those taken as needed (on demand) for the treatment of some symptoms experienced by patients at the time of taking them, further stressing how culture and the rediscovery/diffusion of ancient treatment methods have a fundamental role in the onset of new cases of HILI, in addition to the presence of contaminants in the herbs used or their poor conservation and/or processing described by the authors.

Is there any evidence linking a different sensitivity to the various herbs indicated among populations with different eating habits? And in this case, is there evidence or hypotheses related to these differences? such as different microbiota, greater/lesser tolerance to herbs given by greater/lesser exposure to these herbs?

Minor typo present, e.g. pag 1 line 39: “that” following “2019” or pag 3 line “liver injury are caused my multi-extract” should be “by multi-extract”. I suggest further checking for these typo, however the article is well written.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Title: Herbal and Dietary Supplement Induced Liver Injury: A Review of the Recent Literature

This review article highlights the misuse of many herbal and dietary supplements and associated liver injury, as well as the new promising therapeutic herbal medicine for liver disease. The author has described the various herbal ingredients responsible for liver disease, the mode of action, and their current regulations on usage. The review is a good fit for the scientific community to understand herbal misuse and herbal-induced liver injury and formulate new herbal medication. There are a few minor comments that need to be addressed are following.

1. A few parts of the manuscript require minor editing.

2. All the botanical names of the mentioned herbs should be in italics.

3. Section 8 needs to be rewritten.

4. the author is expected to reduce the word count in the overall manuscript and condense the conclusion into a single paragraph.

A few parts of the manuscript require minor editing.

Author Response

Please see the attachment.

Author Response File: Author Response.docx