Title: Remnant cholesterol/high-density lipoprotein cholesterol ratio is a new powerful tool for
identifying non-alcoholic fatty liver disease
Version: 2 Date: 02 Jan 2022
Reviewer's report:
This is an interesting cross-sectional study on the role of remnant cholesterol/high-density
lipoprotein cholesterol ratio and NAFLD in a large serie of adult subjects screened for NAFLD
by abdominal ultrasound. The Authors conclude that (RC/ HDL-C) ratio may be a new powerful
tool for identifying non-alcoholic fatty liver disease.
However, patient’s selection (excluding those with impaired fasting glucose and/or diabetes and
those taking oral medications at baseline) may have ended to an atypical low/normal weight
NAFLD population. In fact, most NAFLD patients are overweight/obese, have diabetes and the
metabolic syndrome and therefore most of them are under polytherapy. In my opinion, these
selection bias can cause interpretation problems and indicate conclusions that are difficult to
extend to the large number of subjects with NAFLD. Therefore, it would be more correct from
a methodological point of view to consider the whole population of subjects with NAFLD and
to analyze diabetes and drug therapies as independent variables in multivariate analyses.
Besides, there are some issues that need to be addressed/clarified to ensure that the data fully
support the statements and conclusions made.
I suggest that the Authors give some comments on the following points:
1. In the summary and the text, change “may be an effective predictor of NAFLD risk” with
“may be associated to NAFLD”, since this is not a prospective study.
2. The Authors say (line 57) that “under fasting conditions, RC is cholesterol-containing very-
low-density lipoprotein, intermediate-density lipoprotein and chylomicron remnants”. This is
not correct. Under fasting condition, RLP-C is the cholesterol contained in very-low-density
lipoproteins, which originate in the liver, and in their relatively TG-depleted remnants (IDL),
while chylomicron remnants are present only in non-fasting condition.
3. In addition to the references reported in line 63, a further study demonstrated that NAFLD
was independently associated with higher circulating RLP-C, and that high RLP-C levels were
predictive of major cardiovascular and cerebrovascular events in patients with NAFLD (J. Clin.
Med. 2018, 7, 378; doi:10.3390/jcm7110378).
Title: Remnant cholesterol/high-density lipoprotein cholesterol ratio is a new powerful tool for
identifying non-alcoholic fatty liver disease
Version: 2 Date: 02 Jan 2022
Reviewer's report:
This is an interesting cross-sectional study on the role of remnant cholesterol/high-density
lipoprotein cholesterol ratio and NAFLD in a large serie of adult subjects screened for NAFLD
by abdominal ultrasound. The Authors conclude that (RC/ HDL-C) ratio may be a new powerful
tool for identifying non-alcoholic fatty liver disease.
However, patient’s selection (excluding those with impaired fasting glucose and/or diabetes and
those taking oral medications at baseline) may have ended to an atypical low/normal weight
NAFLD population. In fact, most NAFLD patients are overweight/obese, have diabetes and the
metabolic syndrome and therefore most of them are under polytherapy. In my opinion, these
selection bias can cause interpretation problems and indicate conclusions that are difficult to
extend to the large number of subjects with NAFLD. Therefore, it would be more correct from
a methodological point of view to consider the whole population of subjects with NAFLD and
to analyze diabetes and drug therapies as independent variables in multivariate analyses.
Besides, there are some issues that need to be addressed/clarified to ensure that the data fully
support the statements and conclusions made.
I suggest that the Authors give some comments on the following points:
1. In the summary and the text, change “may be an effective predictor of NAFLD risk” with
“may be associated to NAFLD”, since this is not a prospective study.
2. The Authors say (line 57) that “under fasting conditions, RC is cholesterol-containing very-
low-density lipoprotein, intermediate-density lipoprotein and chylomicron remnants”. This is
not correct. Under fasting condition, RLP-C is the cholesterol contained in very-low-density
lipoproteins, which originate in the liver, and in their relatively TG-depleted remnants (IDL),
while chylomicron remnants are present only in non-fasting condition.
3. In addition to the references reported in line 63, a further study demonstrated that NAFLD
was independently associated with higher circulating RLP-C, and that high RLP-C levels were
predictive of major cardiovascular and cerebrovascular events in patients with NAFLD (J. Clin.
Med. 2018, 7, 378; doi:10.3390/jcm7110378).
Please review this paper.
user
Title: Remnant cholesterol/high-density lipoprotein cholesterol ratio is a new powerful tool for
identifying non-alcoholic fatty liver disease
Version: 2 Date: 02 Jan 2022
Reviewer's report:
This is an interesting cross-sectional study on the role of remnant cholesterol/high-density
lipoprotein cholesterol ratio and NAFLD in a large serie of adult subjects screened for NAFLD
by abdominal ultrasound. The Authors conclude that (RC/ HDL-C) ratio may be a new powerful
tool for identifying non-alcoholic fatty liver disease.
However, patient’s selection (excluding those with impaired fasting glucose and/or diabetes and
those taking oral medications at baseline) may have ended to an atypical low/normal weight
NAFLD population. In fact, most NAFLD patients are overweight/obese, have diabetes and the
metabolic syndrome and therefore most of them are under polytherapy. In my opinion, these
selection bias can cause interpretation problems and indicate conclusions that are difficult to
extend to the large number of subjects with NAFLD. Therefore, it would be more correct from
a methodological point of view to consider the whole population of subjects with NAFLD and
to analyze diabetes and drug therapies as independent variables in multivariate analyses.
Besides, there are some issues that need to be addressed/clarified to ensure that the data fully
support the statements and conclusions made.
I suggest that the Authors give some comments on the following points:
1. In the summary and the text, change “may be an effective predictor of NAFLD risk” with
“may be associated to NAFLD”, since this is not a prospective study.
2. The Authors say (line 57) that “under fasting conditions, RC is cholesterol-containing very-
low-density lipoprotein, intermediate-density lipoprotein and chylomicron remnants”. This is
not correct. Under fasting condition, RLP-C is the cholesterol contained in very-low-density
lipoproteins, which originate in the liver, and in their relatively TG-depleted remnants (IDL),
while chylomicron remnants are present only in non-fasting condition.
3. In addition to the references reported in line 63, a further study demonstrated that NAFLD
was independently associated with higher circulating RLP-C, and that high RLP-C levels were
predictive of major cardiovascular and cerebrovascular events in patients with NAFLD (J. Clin.
Med. 2018, 7, 378; doi:10.3390/jcm7110378).
assistant