Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 16 Feb 2025
Reviewer's report:
Dear sir,  thank you for opportunity to review manuscript: Cholesterol-modified prognostic
nutritional index as an independent prognostic biomarker in primary biliary cholangitis patients.
The authors investigated the effect of nutritional indexes (nutritional status -CONUT, geriatric
nutritional risk index - GNRI, prognostic nutritional index  PNI, and cholesterol-modified
prognostic nutritional index - CPNI)  on the prognosis of patients with primary biliary cholangitis
(PBC).
Although the idea is interesting, the paper requires a major revision.
Abstract: It should be noted in the abstract that patients were treated with UDCA. The length
of follow-up of the patient cohort should also be stated and basic demographic data of patients
with PBC should be provided. A more detailed presentation of the results is needed.
Introduction: This part requires modification. It should be noted at the beginning of the chapter
that the incidence of PBC in advanced countries is stable, but the prevalence is increasing, which
is probably associated with better diagnosis of the disease in the early stages  (PMID: 34239845).
PBC diagnostic criteria must be written (ref. 2; PMID: 28427765). It should be added that a
small proportion of patients with PBC have an overlap with autoimmune hepatitis or primary
sclerosing cholangitis; these patients have a worse prognosis (PMID: 18067956).  Please add the
sentences: UDCA is the first choice of treatment for PBC. There are several prognostic scoring
systems that predict the prognosis of PBC patients treated with UDCA (PMID: 36593158), but
there have been no published data on the prognostic role of nutritional factors in predicting the
prognosis of PBC patients. Please remove sentences that are not correctly worded: insufficient
bile acids released into the duodenum contribute to the development of malabsorption, energy
malnutrition, and slow progressive weight loss.  Although the overall 5-year survival rate of
patients with PBC is 80–90%, but can differ significantly among individual.
Study design and data selection: Please add information if you included patients who received
second-line treatment for PBC (fibrates, obeticholic acid, etc.) . Figure 1. Please specify
numerically the causes of patient exclusion.
Definition of malnutrition: Scoring systems assessing malnutrition include albumin, cholesterol
and lymphocyte count. In cirrhosis, albumin and cholesterol are decreased (cholesterol levels,
on the other hand, may rise by progression of cholestasis), and probably lymphocyte counts as
well.  This is a significant limitation of the assessment of malnutrition in cirrhotics.
Results: Please add duration of follow-up of PBC patients.  Table 2.: please add the rows: number
and percentage of patients with liver cirrhosis at baseline examination; duration of the follow-
up, lymphocyte counts, response to UDCA (Toronto) and FIB4 (if available). Please divide PBC
patients into those with and without liver cirrhosis. Construct a separate table, with patients with
cirrhosis in the first column and patients without cirrhosis in the second column. The table should
have rows for: age, sex, duration of follow-up, BMI, overweight, underweight, malnutrition,
response to UDCA (Toronto), ALP, platelets, CONUT, GNRI, PNI, CPNI. Calculate statistical
significance for each parameter.  Table 3.: Please include FIB4 into multivariate analysis.
Discussion: The discussion requires editing and must be focused on the issue being studied. It
should be noted that the prevalence of malnutrition in PBC patients has not been adequately
studied. It probably occurs in advanced stages of the disease. Sentence: "Malnutrition was
prevalent in PBC patients with rates ranging from 38–51% according to four different nutritional
assessment tools in our study" isn´t correct, half of PBC patients do not have malnutrition.  Major
limitation of the study is fact, that albumin, cholesterol and lymphocyte count, that are included
in malnutrition scoring systems are decreased also in liver cirrhosis.
My final evaluation is major revision.