Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 03 Dec 2023
Reviewer's report:
The authors addressed a very interesting topic in the field of hepatology: how to optimize the
management of patients with HCC particularly patients with HCC and normal values of AFP.
The authors studied the role of a  new tool for the prediction of survival.
Minor revision:
1) change the introduction sentence according to the data reported by AASLD guidelines: HCC
is now the third cause of cancer-related mortality please see : https://www.aasld.org/practice-
guidelines/management-hepatocellular-carcinoma
2) line 67-69  introduction section: this sentence contains a statistical consideration. I suggest
to remove it from introduction
3) line 128-129 ("The mortality rate within one year in the total cohort was 26.2%") this sentence
is a repetition of the sentence reported in lines  127-128
4) in method section clarify the classification used for the grading of HCC: WHO grading
system? Edmondson-Steiner grading system?
Maior
1) it is not clear how the authors managed the variable "radiation".
It is not reported in the manuscript if the authors refer to external radiation or SIRT.
Current guidelines do not recommend external radiation because the real efficacy is under
investigation whereas selective internal radiation therapy (SIRT) is generally used in patients
with HCC.
Probably the authors refer to SIRT (this should be clarified in the method section)
SIRT is generally used in patients with large lesions or in case of vascular invasion who have
per se a low survival rate irrespective of treatment use.
Patients with HCC who underwent SIRT have generally a survival which is lower than 3 years
irrespective of using this treatment.
The use of radiation (SIRT?) associates with clinical elements (e.g. large size, portal vein
thrombosis) which are  generally associated with high mortality.
Therefore the use of radiation per se should not to be considered a factor which improve the
mortality.
This consideration suggest that, irrespective of statistical significance, the clinical  or  reasoned
significance should be addressed.
I suggest the authors to re-evaluate the use of radiation in the nomogram.
2) Portal vein thrombosis is not included in the statistical analysis (not reported in baseline
characteristics and not included in Univariate and Multivariate Analysis).
the presence of portal vein thrombosis (neoplastic thrombosis) is an important factor which may
impact on the survival of patients with HCC.
The authors included in their analysis the marital status but not the portal vein thrombosis which
is more  important. I suggest to add these data in the analysis
3) Did the authors explored the role of hyperbilirubinemia and/or hypoalbuminemia and/or the
number of previous episodes of decompensations? the presence of alteration of kidney function?
Probably they are useful for the creation of a useful nomogram. As an alternative CHILD and
MELD may be used
Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 03 Dec 2023
Reviewer's report:
The authors addressed a very interesting topic in the field of hepatology: how to optimize the
management of patients with HCC particularly patients with HCC and normal values of AFP.
The authors studied the role of a  new tool for the prediction of survival.
Minor revision:
1) change the introduction sentence according to the data reported by AASLD guidelines: HCC
is now the third cause of cancer-related mortality please see : https://www.aasld.org/practice-
guidelines/management-hepatocellular-carcinoma
2) line 67-69  introduction section: this sentence contains a statistical consideration. I suggest
to remove it from introduction
3) line 128-129 ("The mortality rate within one year in the total cohort was 26.2%") this sentence
is a repetition of the sentence reported in lines  127-128
4) in method section clarify the classification used for the grading of HCC: WHO grading
system? Edmondson-Steiner grading system?
Maior
1) it is not clear how the authors managed the variable "radiation".
It is not reported in the manuscript if the authors refer to external radiation or SIRT.
Current guidelines do not recommend external radiation because the real efficacy is under
investigation whereas selective internal radiation therapy (SIRT) is generally used in patients
with HCC.
Probably the authors refer to SIRT (this should be clarified in the method section)
SIRT is generally used in patients with large lesions or in case of vascular invasion who have
per se a low survival rate irrespective of treatment use.
Patients with HCC who underwent SIRT have generally a survival which is lower than 3 years
irrespective of using this treatment.
The use of radiation (SIRT?) associates with clinical elements (e.g. large size, portal vein
thrombosis) which are  generally associated with high mortality.
Therefore the use of radiation per se should not to be considered a factor which improve the
mortality.
This consideration suggest that, irrespective of statistical significance, the clinical  or  reasoned
significance should be addressed.
I suggest the authors to re-evaluate the use of radiation in the nomogram.
2) Portal vein thrombosis is not included in the statistical analysis (not reported in baseline
characteristics and not included in Univariate and Multivariate Analysis).
the presence of portal vein thrombosis (neoplastic thrombosis) is an important factor which may
impact on the survival of patients with HCC.
The authors included in their analysis the marital status but not the portal vein thrombosis which
is more  important. I suggest to add these data in the analysis
3) Did the authors explored the role of hyperbilirubinemia and/or hypoalbuminemia and/or the
number of previous episodes of decompensations? the presence of alteration of kidney function?
Probably they are useful for the creation of a useful nomogram. As an alternative CHILD and
MELD may be used
Please review this paper.
user
Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 03 Dec 2023
Reviewer's report:
The authors addressed a very interesting topic in the field of hepatology: how to optimize the
management of patients with HCC particularly patients with HCC and normal values of AFP.
The authors studied the role of a  new tool for the prediction of survival.
Minor revision:
1) change the introduction sentence according to the data reported by AASLD guidelines: HCC
is now the third cause of cancer-related mortality please see : https://www.aasld.org/practice-
guidelines/management-hepatocellular-carcinoma
2) line 67-69  introduction section: this sentence contains a statistical consideration. I suggest
to remove it from introduction
3) line 128-129 ("The mortality rate within one year in the total cohort was 26.2%") this sentence
is a repetition of the sentence reported in lines  127-128
4) in method section clarify the classification used for the grading of HCC: WHO grading
system? Edmondson-Steiner grading system?
Maior
1) it is not clear how the authors managed the variable "radiation".
It is not reported in the manuscript if the authors refer to external radiation or SIRT.
Current guidelines do not recommend external radiation because the real efficacy is under
investigation whereas selective internal radiation therapy (SIRT) is generally used in patients
with HCC.
Probably the authors refer to SIRT (this should be clarified in the method section)
SIRT is generally used in patients with large lesions or in case of vascular invasion who have
per se a low survival rate irrespective of treatment use.
Patients with HCC who underwent SIRT have generally a survival which is lower than 3 years
irrespective of using this treatment.
The use of radiation (SIRT?) associates with clinical elements (e.g. large size, portal vein
thrombosis) which are  generally associated with high mortality.
Therefore the use of radiation per se should not to be considered a factor which improve the
mortality.
This consideration suggest that, irrespective of statistical significance, the clinical  or  reasoned
significance should be addressed.
I suggest the authors to re-evaluate the use of radiation in the nomogram.
2) Portal vein thrombosis is not included in the statistical analysis (not reported in baseline
characteristics and not included in Univariate and Multivariate Analysis).
the presence of portal vein thrombosis (neoplastic thrombosis) is an important factor which may
impact on the survival of patients with HCC.
The authors included in their analysis the marital status but not the portal vein thrombosis which
is more  important. I suggest to add these data in the analysis
3) Did the authors explored the role of hyperbilirubinemia and/or hypoalbuminemia and/or the
number of previous episodes of decompensations? the presence of alteration of kidney function?
Probably they are useful for the creation of a useful nomogram. As an alternative CHILD and
MELD may be used
assistant