Title: PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese
patients with histopathologically-confirmed NAFLD
Version: 1 Date: 09 Oct 2021
Reviewer's report:
This is a retrospective analysis of risk factors for CVD, malignancy and liver-related events
in histo-pathologically confirmed NAFLD patients. The results showed that FIB4-index # 2.67
was a risk factor for the occurrence of each event.
(Major comments)
It is very interesting that the PNPLA3 CC type has a higher risk of cardiovascular events.
It would be great if you could tell us if there is a tendency for patients with PNPLA3 CC type
to have more complications related to CVD risk, for example DM or dyslipidemia. In the past,
it has been reported that fasting glucose and TG levels are higher in PNPLA3 CC patients[1].
It is necessary to adjust for these values in the analysis.
[1] Hotta K, Sekine A: Association of the rs738409 polymorphism in PNPLA3 with liver damage
and the development of nonalcoholic fatty liver disease. BMC Med Genet 2010, 11:172.
This study is a single-center analysis. I would be grateful if you could reanalyze the results in
a multi-center validation.
Is this a retrospective study of all patients, or only of those with adequate follow-up, as described
in the "Follow-up" section? Either way, as it is a retrospective study, it has one bias that needs
to be mentioned in the limitations.
Why did you not evaluate the association between histopathology, such as fibrosis, and the
event?
It would be better to state whether or not NAFLD has been diagnosed by an independent central
histological review.
The total number of histopathological findings in Table 1 is different from the total number in
Table 2, which should be reviewed.
(Minor comments)
Fib-4 index is not official; FIB-4 is the correct notation.
Does "stage" in Table 1 refer to the fibrosis stage? It needs to be corrected.
I think "diagnoss" in Page 10, Line 169 is a mistake, so please correct it.
Title: PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese
patients with histopathologically-confirmed NAFLD
Version: 1 Date: 09 Oct 2021
Reviewer's report:
This is a retrospective analysis of risk factors for CVD, malignancy and liver-related events
in histo-pathologically confirmed NAFLD patients. The results showed that FIB4-index # 2.67
was a risk factor for the occurrence of each event.
(Major comments)
It is very interesting that the PNPLA3 CC type has a higher risk of cardiovascular events.
It would be great if you could tell us if there is a tendency for patients with PNPLA3 CC type
to have more complications related to CVD risk, for example DM or dyslipidemia. In the past,
it has been reported that fasting glucose and TG levels are higher in PNPLA3 CC patients[1].
It is necessary to adjust for these values in the analysis.
[1] Hotta K, Sekine A: Association of the rs738409 polymorphism in PNPLA3 with liver damage
and the development of nonalcoholic fatty liver disease. BMC Med Genet 2010, 11:172.
This study is a single-center analysis. I would be grateful if you could reanalyze the results in
a multi-center validation.
Is this a retrospective study of all patients, or only of those with adequate follow-up, as described
in the "Follow-up" section? Either way, as it is a retrospective study, it has one bias that needs
to be mentioned in the limitations.
Why did you not evaluate the association between histopathology, such as fibrosis, and the
event?
It would be better to state whether or not NAFLD has been diagnosed by an independent central
histological review.
The total number of histopathological findings in Table 1 is different from the total number in
Table 2, which should be reviewed.
(Minor comments)
Fib-4 index is not official; FIB-4 is the correct notation.
Does "stage" in Table 1 refer to the fibrosis stage? It needs to be corrected.
I think "diagnoss" in Page 10, Line 169 is a mistake, so please correct it.
Please review this paper.
user
Title: PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese
patients with histopathologically-confirmed NAFLD
Version: 1 Date: 09 Oct 2021
Reviewer's report:
This is a retrospective analysis of risk factors for CVD, malignancy and liver-related events
in histo-pathologically confirmed NAFLD patients. The results showed that FIB4-index # 2.67
was a risk factor for the occurrence of each event.
(Major comments)
It is very interesting that the PNPLA3 CC type has a higher risk of cardiovascular events.
It would be great if you could tell us if there is a tendency for patients with PNPLA3 CC type
to have more complications related to CVD risk, for example DM or dyslipidemia. In the past,
it has been reported that fasting glucose and TG levels are higher in PNPLA3 CC patients[1].
It is necessary to adjust for these values in the analysis.
[1] Hotta K, Sekine A: Association of the rs738409 polymorphism in PNPLA3 with liver damage
and the development of nonalcoholic fatty liver disease. BMC Med Genet 2010, 11:172.
This study is a single-center analysis. I would be grateful if you could reanalyze the results in
a multi-center validation.
Is this a retrospective study of all patients, or only of those with adequate follow-up, as described
in the "Follow-up" section? Either way, as it is a retrospective study, it has one bias that needs
to be mentioned in the limitations.
Why did you not evaluate the association between histopathology, such as fibrosis, and the
event?
It would be better to state whether or not NAFLD has been diagnosed by an independent central
histological review.
The total number of histopathological findings in Table 1 is different from the total number in
Table 2, which should be reviewed.
(Minor comments)
Fib-4 index is not official; FIB-4 is the correct notation.
Does "stage" in Table 1 refer to the fibrosis stage? It needs to be corrected.
I think "diagnoss" in Page 10, Line 169 is a mistake, so please correct it.
assistant