Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 18 Nov 2023
Reviewer's report:
My comments to the authors:
A. General Comments:
1. The article would have been more clinically helpful, if it had been planned to give information
on the outcome of the AFP-negative HCC patients (ANHC) at a pretreatment stage, i.e., after
the initial evaluation establishing the diagnosis of ANHC, including a liver biopsy, and before
starting any treatment. Treatment may vary in time and place and it is not a stable factor. The
posttreatment prediction of survival of ANHC patients may provide some useful information
but, to my opinion, is practically of less clinical importance.
2. English language use is excellent, but some typing errors in the text must be corrected.
B. Major Comments:
1. (Page 1, Line 46): The relative weight and the level of significance of each one of the
prognostic factors must appear in the section of Results in the Abstract.
2. (Page 4, Line 81): Authors should explain:
i. Whether the “tumor size” was the maximum diameter (in cm) or the area (in cm2) of the largest
or the summation area of all tumors.
ii. In the case of multiple small foci their effect on survival may not be the same as that of a
single large tumor of the same area.
iii. Patients with coexisting portal vein invasion were included in the tested groups?  Portal vein
invasion is a factor strongly affecting patient survival.
iv. Was the etiology of the underlying liver disease taken into account as a factor of survival?
3. (Page 4, Line 86): Was the etiology of the underlying liver disease taken into account as a
factor of survival?
4. (Page 6, Line 133): The hazard ratios and the p-values of the significant factors must appear
at this point and not only in Table 2.
5. (Page 6, Line 153): TNM is a pathological/clinical diagnosis. However, it is not fair to
compare prognosis provided by TNM to that by the present nomogram model, since the later
includes also therapeutic interventions able to modify OS/CSS. The authors must accept this
comment and modify or eliminate this section and the associated Figures.
6. (Page 9, Line 398): Figures 2 and 3 must appear in the Supplementary Section of this article.
7.
C. Minor Comment:
1. (Page 2, Line 60): “<20ng/mL”. Please make corrections and elsewhere in the text.
2. (Page 7, Line 196): “…have AFP values at the normal range…”
3. (Page 9, Line 225): …stage Ia (?).
4. (Page 14, Line 436): Authors should mention in a footnote that the numbers outside and in
parentheses correspond to the number of patients (n) and the percentage of the respective group
(%).
5. (Page 20, Table 2): Please clarify what a p-value equaling zero (0) stands for. Zero should
be replaced by the real p-value.
6. (Page 20, Table 2): Caucasian ethnicity is missing. Please clarify.
7. (Page 20, Table 2): Please explain all abbreviations in a footnote.
Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 18 Nov 2023
Reviewer's report:
My comments to the authors:
A. General Comments:
1. The article would have been more clinically helpful, if it had been planned to give information
on the outcome of the AFP-negative HCC patients (ANHC) at a pretreatment stage, i.e., after
the initial evaluation establishing the diagnosis of ANHC, including a liver biopsy, and before
starting any treatment. Treatment may vary in time and place and it is not a stable factor. The
posttreatment prediction of survival of ANHC patients may provide some useful information
but, to my opinion, is practically of less clinical importance.
2. English language use is excellent, but some typing errors in the text must be corrected.
B. Major Comments:
1. (Page 1, Line 46): The relative weight and the level of significance of each one of the
prognostic factors must appear in the section of Results in the Abstract.
2. (Page 4, Line 81): Authors should explain:
i. Whether the “tumor size” was the maximum diameter (in cm) or the area (in cm2) of the largest
or the summation area of all tumors.
ii. In the case of multiple small foci their effect on survival may not be the same as that of a
single large tumor of the same area.
iii. Patients with coexisting portal vein invasion were included in the tested groups?  Portal vein
invasion is a factor strongly affecting patient survival.
iv. Was the etiology of the underlying liver disease taken into account as a factor of survival?
3. (Page 4, Line 86): Was the etiology of the underlying liver disease taken into account as a
factor of survival?
4. (Page 6, Line 133): The hazard ratios and the p-values of the significant factors must appear
at this point and not only in Table 2.
5. (Page 6, Line 153): TNM is a pathological/clinical diagnosis. However, it is not fair to
compare prognosis provided by TNM to that by the present nomogram model, since the later
includes also therapeutic interventions able to modify OS/CSS. The authors must accept this
comment and modify or eliminate this section and the associated Figures.
6. (Page 9, Line 398): Figures 2 and 3 must appear in the Supplementary Section of this article.
7.
C. Minor Comment:
1. (Page 2, Line 60): “<20ng/mL”. Please make corrections and elsewhere in the text.
2. (Page 7, Line 196): “…have AFP values at the normal range…”
3. (Page 9, Line 225): …stage Ia (?).
4. (Page 14, Line 436): Authors should mention in a footnote that the numbers outside and in
parentheses correspond to the number of patients (n) and the percentage of the respective group
(%).
5. (Page 20, Table 2): Please clarify what a p-value equaling zero (0) stands for. Zero should
be replaced by the real p-value.
6. (Page 20, Table 2): Caucasian ethnicity is missing. Please clarify.
7. (Page 20, Table 2): Please explain all abbreviations in a footnote.
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: 18 Nov 2023
Reviewer's report:
My comments to the authors:
A. General Comments:
1. The article would have been more clinically helpful, if it had been planned to give information
on the outcome of the AFP-negative HCC patients (ANHC) at a pretreatment stage, i.e., after
the initial evaluation establishing the diagnosis of ANHC, including a liver biopsy, and before
starting any treatment. Treatment may vary in time and place and it is not a stable factor. The
posttreatment prediction of survival of ANHC patients may provide some useful information
but, to my opinion, is practically of less clinical importance.
2. English language use is excellent, but some typing errors in the text must be corrected.
B. Major Comments:
1. (Page 1, Line 46): The relative weight and the level of significance of each one of the
prognostic factors must appear in the section of Results in the Abstract.
2. (Page 4, Line 81): Authors should explain:
i. Whether the “tumor size” was the maximum diameter (in cm) or the area (in cm2) of the largest
or the summation area of all tumors.
ii. In the case of multiple small foci their effect on survival may not be the same as that of a
single large tumor of the same area.
iii. Patients with coexisting portal vein invasion were included in the tested groups?  Portal vein
invasion is a factor strongly affecting patient survival.
iv. Was the etiology of the underlying liver disease taken into account as a factor of survival?
3. (Page 4, Line 86): Was the etiology of the underlying liver disease taken into account as a
factor of survival?
4. (Page 6, Line 133): The hazard ratios and the p-values of the significant factors must appear
at this point and not only in Table 2.
5. (Page 6, Line 153): TNM is a pathological/clinical diagnosis. However, it is not fair to
compare prognosis provided by TNM to that by the present nomogram model, since the later
includes also therapeutic interventions able to modify OS/CSS. The authors must accept this
comment and modify or eliminate this section and the associated Figures.
6. (Page 9, Line 398): Figures 2 and 3 must appear in the Supplementary Section of this article.
7.
C. Minor Comment:
1. (Page 2, Line 60): “<20ng/mL”. Please make corrections and elsewhere in the text.
2. (Page 7, Line 196): “…have AFP values at the normal range…”
3. (Page 9, Line 225): …stage Ia (?).
4. (Page 14, Line 436): Authors should mention in a footnote that the numbers outside and in
parentheses correspond to the number of patients (n) and the percentage of the respective group
(%).
5. (Page 20, Table 2): Please clarify what a p-value equaling zero (0) stands for. Zero should
be replaced by the real p-value.
6. (Page 20, Table 2): Caucasian ethnicity is missing. Please clarify.
7. (Page 20, Table 2): Please explain all abbreviations in a footnote.
assistant