Review for 10.1186/s12876-022-02406-7 (2022)

Reviewer’s report
Title: 
The impact of serum thyroid-stimulation hormone levels on the outcome
of hepatitis B virus related acute-on-chronic liver failure: an observational study
Version: 
3 
Date: 
27 Feb 2022
Reviewer's report:
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This manuscript is an exciting study as it documents the critical role of the liver
in the metabolism of thyroid hormones. The objective of this large cohort study
was to determine the predictive value of serum TSH levels among patients with
HBV-related ACLF. However, the target population used only a single cohort
among patients with ACLF. There were no comparisons with a healthy cohort
nor a cohort with ACLF with normal TSH. 
There are additional concerns that cast doubts on the conclusion... Firstly the
authors did not have a healthy control nor those with compensated cirrhosis. It
was a single observation among cirrhotic patients. Secondly, 
the authors used a
single-point determinant of TSH. It was not correlated on the average level or
whether the TSH levels fluctuated with HE improvement or decreasing Ascites. 
Furthermore, there were studies correlating only low levels of FT3 but normal
FT4. Will this observation affect the conclusion? Thirdly, the arbitrary definition
of classification of subgroups based on the level was not explained. How did the
authors develop the tiered level of mild, moderate, and severe elevation of TSH.?
This was not defined in the methodology. 
Regarding TABLE 1: Demographics show differences in p-value, meaning
Baseline characteristics are not comparable. Moreover, the patients in Group III
had more treatment than those in Group I and II. Knowing this affects the risk of
decompensation, will it also affect the conclusion. 
Lastly, being a 
retrospective study and therefore cannot be used for predictive
assessment of risk factors, this study is the level of 
TSH. The retrospective
cohort tests a potential hypothesis regarding suspected risk factors concerning an
outcome. However, a hasty conclusion is to isolate only one element, TSH,
without correlating the other factors like age, level of CPC, and MELD as
covariates. More evidence should be drawn, and confounders should also be
listed in the findings. 
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes