Review for 10.1186/s12876-022-02121-3 (2022)

Reviewer’s report
Title: 
Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal
cell carcinoma patients: Two case reports assessed for causality using the
updated RUCAM and review of the literature
Version: 
1 
Date: 
05 Oct 2021
Reviewer: 
Rolf Teschke
Reviewer's report:
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Please overwrThis is an attempt to present two potentially interesting DILI cases.
However, there is a methodology problem of correct causality assessment that
invalidates current conclusions. Thus, important improvement is essential.
Major points:
1. DILI cases were not correctly assessed for causality using the updated
RUCAM published in 2016. So please do that and incorporate details in the text.
Clarify this issue in the abstract, and under methods, results, and discussion.
Case 1, discuss hypoxic hepatopathy due to low Hb. Second patients can well be
assessed by RUCAM, consider also Amoxy-Clav, use and provide for each drug
an individual RUCAM scale.
2. Please make your title more specific and stimulating for the readers. Expand
"two case reports" to: two cases reports assessed for causality using the updated
RUCAM. Also, replace hepatotoxicity by: liver injury, here and elsewhere in the
text.
3. Condense the discussion section by at least 80%, as much is repetitive. Focus
on main issues, CYP discussion is much too long, also speculative if based in
experimental studies. Add discussion on causality assessment using RUCAM,
preferentially its updated version. Delete sentences on Naranjo. 
Minor points:
1. Add country on title page after Olomouc. 
2. L39, Herein we report: correct induces to: induced.
3. L31, signatures associated … correct Roussel-Uclaf to: Roussel Uclaf.
4. L 9, intensive care… what does that mean: CMV..?
5. L 36 and elsewhere in the text. Hepatotoxicity is a feared….replace side by
adverse.
6. L3 may be useful.. What is that: (30)NAC? At other places, move references
at the end of the sentence, do not keep them outside.
7. Twice background?
8. Introduction needs condensation by at least half. Highly repetitive with other
areas of the text.
9. Background L27, inhibitorsused, what do you mean? Same line, (RCC).
Hepatotoxicity, please correct empty space. Typos are signs that author and co-
authors did not carefully edit the paper, case data as presented are hopefully of
better quality.
10. Hepatic abnormalities, what do you mean? laboratory?
11. Second background, whenever you describe case details, please add whether
such cases were evaluated by RUCAM, otherwise you better delete.
12. Case 1, male, female, or diverse??? OD, expand. Was HEV excluded? Peptic
ulcers, where? Helicobacter pylori?? 
13. Heading of case 2? Gender? DILI by Amox-Clav???
14. Avoid para with a single sentence.
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