Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 16 Feb 2025
Reviewer:  Martin Janicko
Reviewer's report:
Comments to the authors:
Abstract – Please state explicitly the objective of the current manuscript – e.g. development and
validation of an improved prognostic index to assess the survival.
Shorten the background section of the abstract.
Methods – explicitly state the type of research e.g. observational retrospective longitudinal
study. Write the method of patient recruitment – e.g. consecutive patients from clinical care
database.
State the length of followup and the proportion of patients reaching primary outcome (death).
Results in the abstract should also include model fit of the overall predictive model and the ORs
of major predictors.
Conclusion – please state that no validation was carried out.
Manuscript describes a retrospective longitudinal study that aimed to develop a predictive score
for survival of PBC patients that includes nutrition status as a major predictor. The idea is
important, but the study carries all the biases of retrospective study including selection bias amd
missing data bias.
The language is sometimes difficult to understand. (e.g. A progressive disorder in the processes
of bile secretion and enterohepatic bile salt circulation in patients with PBC in its early stages
leads to an insufficient release of bile acids into the bowel and their entry into the systemic
circulation)
Introduction is adequate.
Methods section is adequate, the study is reproducible with stated methods.
Results
There is no information on the length of follow-up and  the proportion of patients who died
except Kaplan – Meyer curves. There is no number at risk for KAplan Mayer.
Therefore the risk of data ovefitting cannot be assessed (max 1 predictor per 10 outcomes). Also
multiple models are constructed for single outcome, no adjustment for multiple comparisons
has been made.
Selection of covariates is limited by the retrospective nature of the study, but one major
missing covariate introduces significant bias – baseline fibrosis. Authors should include VCTE
preferably, or at least FIB-4 score as a covariate in the models.
Another major covariate that is missing and basically invalidates the conclusion is the response
to treatment. Although authors state that all patients were on UDCA treatment, the rate of
response to UDCA is only about 60% and non-responders have significantly worse prognosis,
as well as nutritional status.
Comparisons with other prognostic scores are missing (GLOBE, UK-PBC).
Biggest problem is that the study is missing validation cohort.
Discussion
Authors reiterate the results of the study, but the comparisons with other published data is
missing. E.g. authors state “Malnutrition was prevalent in PBC patients with rates ranging from
38% to 51% according to four different nutritional assessment tools in our study.“, but do not
compare this to other available data.
Such context is missing for other results as well.
Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 16 Feb 2025
Reviewer:  Martin Janicko
Reviewer's report:
Comments to the authors:
Abstract – Please state explicitly the objective of the current manuscript – e.g. development and
validation of an improved prognostic index to assess the survival.
Shorten the background section of the abstract.
Methods – explicitly state the type of research e.g. observational retrospective longitudinal
study. Write the method of patient recruitment – e.g. consecutive patients from clinical care
database.
State the length of followup and the proportion of patients reaching primary outcome (death).
Results in the abstract should also include model fit of the overall predictive model and the ORs
of major predictors.
Conclusion – please state that no validation was carried out.
Manuscript describes a retrospective longitudinal study that aimed to develop a predictive score
for survival of PBC patients that includes nutrition status as a major predictor. The idea is
important, but the study carries all the biases of retrospective study including selection bias amd
missing data bias.
The language is sometimes difficult to understand. (e.g. A progressive disorder in the processes
of bile secretion and enterohepatic bile salt circulation in patients with PBC in its early stages
leads to an insufficient release of bile acids into the bowel and their entry into the systemic
circulation)
Introduction is adequate.
Methods section is adequate, the study is reproducible with stated methods.
Results
There is no information on the length of follow-up and  the proportion of patients who died
except Kaplan – Meyer curves. There is no number at risk for KAplan Mayer.
Therefore the risk of data ovefitting cannot be assessed (max 1 predictor per 10 outcomes). Also
multiple models are constructed for single outcome, no adjustment for multiple comparisons
has been made.
Selection of covariates is limited by the retrospective nature of the study, but one major
missing covariate introduces significant bias – baseline fibrosis. Authors should include VCTE
preferably, or at least FIB-4 score as a covariate in the models.
Another major covariate that is missing and basically invalidates the conclusion is the response
to treatment. Although authors state that all patients were on UDCA treatment, the rate of
response to UDCA is only about 60% and non-responders have significantly worse prognosis,
as well as nutritional status.
Comparisons with other prognostic scores are missing (GLOBE, UK-PBC).
Biggest problem is that the study is missing validation cohort.
Discussion
Authors reiterate the results of the study, but the comparisons with other published data is
missing. E.g. authors state “Malnutrition was prevalent in PBC patients with rates ranging from
38% to 51% according to four different nutritional assessment tools in our study.“, but do not
compare this to other available data.
Such context is missing for other results as well.
Please review this paper.
user
Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 16 Feb 2025
Reviewer:  Martin Janicko
Reviewer's report:
Comments to the authors:
Abstract – Please state explicitly the objective of the current manuscript – e.g. development and
validation of an improved prognostic index to assess the survival.
Shorten the background section of the abstract.
Methods – explicitly state the type of research e.g. observational retrospective longitudinal
study. Write the method of patient recruitment – e.g. consecutive patients from clinical care
database.
State the length of followup and the proportion of patients reaching primary outcome (death).
Results in the abstract should also include model fit of the overall predictive model and the ORs
of major predictors.
Conclusion – please state that no validation was carried out.
Manuscript describes a retrospective longitudinal study that aimed to develop a predictive score
for survival of PBC patients that includes nutrition status as a major predictor. The idea is
important, but the study carries all the biases of retrospective study including selection bias amd
missing data bias.
The language is sometimes difficult to understand. (e.g. A progressive disorder in the processes
of bile secretion and enterohepatic bile salt circulation in patients with PBC in its early stages
leads to an insufficient release of bile acids into the bowel and their entry into the systemic
circulation)
Introduction is adequate.
Methods section is adequate, the study is reproducible with stated methods.
Results
There is no information on the length of follow-up and  the proportion of patients who died
except Kaplan – Meyer curves. There is no number at risk for KAplan Mayer.
Therefore the risk of data ovefitting cannot be assessed (max 1 predictor per 10 outcomes). Also
multiple models are constructed for single outcome, no adjustment for multiple comparisons
has been made.
Selection of covariates is limited by the retrospective nature of the study, but one major
missing covariate introduces significant bias – baseline fibrosis. Authors should include VCTE
preferably, or at least FIB-4 score as a covariate in the models.
Another major covariate that is missing and basically invalidates the conclusion is the response
to treatment. Although authors state that all patients were on UDCA treatment, the rate of
response to UDCA is only about 60% and non-responders have significantly worse prognosis,
as well as nutritional status.
Comparisons with other prognostic scores are missing (GLOBE, UK-PBC).
Biggest problem is that the study is missing validation cohort.
Discussion
Authors reiterate the results of the study, but the comparisons with other published data is
missing. E.g. authors state “Malnutrition was prevalent in PBC patients with rates ranging from
38% to 51% according to four different nutritional assessment tools in our study.“, but do not
compare this to other available data.
Such context is missing for other results as well.
assistant