Title: Pan-Immune-Inflammation Value and Mortality in The US Adult MASLD: A Nonlinear
NHANES Analysis
Version: 0 Date: 10 May 2025
Reviewer's report:
Zhou et al report an observational association between mortality and an inflammation indicator
in people with metabolic liver stress. The general topic is interesting and relevant since the
vicious synergy of metabolic dysfunction, liver disease and inflammation underlies the risk of
common adverse clinical outcomes. The manuscript is written clearly, the results are presented
well and the authors used standard methodology in the field. The NHANES is a well known
dataset with sufficient size for these types of epidemiological studies.
I am somewhat conflicted about the novelty of this study. The inflammation indicator they used
has been introduced recently, but so have many other various formulas related to inflammation
and fibrosis. However, based on these types of isolated analyses, it is difficult to judge what
additional benefit over existing diagnostics or phenotypic assessment can be gained from e.g.
pan-inflammation value. It would be more useful to benchmark each new formula against
existing biomarkers and then determine if they provide additional value. To make this study
more informative, I would recommend adding a benchmarking section where the PIV is judged
(fairly) against direct measures such as CRP and formulas such as other immune cell ratios etc
etc. Importantly, by keeping the dataset and statistical methods exactly the same, the reader
would get an accurate understanding of the strengths and weaknesses of the PIV.
Minor comment: please tidy up the supplement tables as the high decimal precision of the
numbers make them hard to read.
Title: Pan-Immune-Inflammation Value and Mortality in The US Adult MASLD: A Nonlinear
NHANES Analysis
Version: 0 Date: 10 May 2025
Reviewer's report:
Zhou et al report an observational association between mortality and an inflammation indicator
in people with metabolic liver stress. The general topic is interesting and relevant since the
vicious synergy of metabolic dysfunction, liver disease and inflammation underlies the risk of
common adverse clinical outcomes. The manuscript is written clearly, the results are presented
well and the authors used standard methodology in the field. The NHANES is a well known
dataset with sufficient size for these types of epidemiological studies.
I am somewhat conflicted about the novelty of this study. The inflammation indicator they used
has been introduced recently, but so have many other various formulas related to inflammation
and fibrosis. However, based on these types of isolated analyses, it is difficult to judge what
additional benefit over existing diagnostics or phenotypic assessment can be gained from e.g.
pan-inflammation value. It would be more useful to benchmark each new formula against
existing biomarkers and then determine if they provide additional value. To make this study
more informative, I would recommend adding a benchmarking section where the PIV is judged
(fairly) against direct measures such as CRP and formulas such as other immune cell ratios etc
etc. Importantly, by keeping the dataset and statistical methods exactly the same, the reader
would get an accurate understanding of the strengths and weaknesses of the PIV.
Minor comment: please tidy up the supplement tables as the high decimal precision of the
numbers make them hard to read.
Please review this paper.
user
Title: Pan-Immune-Inflammation Value and Mortality in The US Adult MASLD: A Nonlinear
NHANES Analysis
Version: 0 Date: 10 May 2025
Reviewer's report:
Zhou et al report an observational association between mortality and an inflammation indicator
in people with metabolic liver stress. The general topic is interesting and relevant since the
vicious synergy of metabolic dysfunction, liver disease and inflammation underlies the risk of
common adverse clinical outcomes. The manuscript is written clearly, the results are presented
well and the authors used standard methodology in the field. The NHANES is a well known
dataset with sufficient size for these types of epidemiological studies.
I am somewhat conflicted about the novelty of this study. The inflammation indicator they used
has been introduced recently, but so have many other various formulas related to inflammation
and fibrosis. However, based on these types of isolated analyses, it is difficult to judge what
additional benefit over existing diagnostics or phenotypic assessment can be gained from e.g.
pan-inflammation value. It would be more useful to benchmark each new formula against
existing biomarkers and then determine if they provide additional value. To make this study
more informative, I would recommend adding a benchmarking section where the PIV is judged
(fairly) against direct measures such as CRP and formulas such as other immune cell ratios etc
etc. Importantly, by keeping the dataset and statistical methods exactly the same, the reader
would get an accurate understanding of the strengths and weaknesses of the PIV.
Minor comment: please tidy up the supplement tables as the high decimal precision of the
numbers make them hard to read.
assistant