Title: The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic
abnormalities in Brazilian patients with chronic hepatitis C
Version: 1 Date: 04 Dec 2020
Reviewer's report:
The study reports the association of two common steatogenic variants in the genes PNPLA3
and TM6SF2 with liver disease in 365 Brazilian patients with HCV, and 134 controls. Liver
disease was evaluated by histology. The main finding was that neither variant was associated
with increased steatosis or fibrosis in the cohort.
Comments
1. Please state in the abstract that steatosis and fibrosis were evaluated by histology.
2. It would be interesting to see associations for a combined risk score (PNPLA3 + TM6SF2).
3. How many had missing covariates? It seems from Table 1 that the dataset was almost
complete, with only a few missing information on some of the covaraites. Please add a statement
to this effect (ie. what was the max % of missing values for any covariate?) in the Methods
section.
4. the number of significant digits in numbers is excessive, throughout the manuscript (both
in the text and tables). Ie. percentages could be rounded to 1 digit after the period (instead of
30.49%, just use 30.5%), 'TM6SF2 and PNPLA3 heterozygosity were 0.1977 and 0.5608' should
be 0.20 and 0.56. P-values could be reported with 3 significant digits after the period. Ie. 0.044
instead of 0.0443. ORs should be with 2 digits after the period: '1.95, 95% CI 1.01-3.79' instead
of '1.9531 .953, 95% CI 1.009-3.788'.
5. The moderate sample size (and consequently low power) should be mentioned as a limitation.
6. The nucleotide position for the TM6SF2 variant is c.499C>T and not c.449 as stated
throughout. Please correct.
Minor
1. page 4 line 19: 'The wild allele (C allele)' , better: 'the common C allele'
2. Page 4, line 21: delete 'the' in front of TM6SF2.
3. page 13, line 13: 'PNPLA3 gene was not in Hardy-Weinberg equilibrium, what precludes firm
conclusions'. 'what' should be 'which'.
Title: The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic
abnormalities in Brazilian patients with chronic hepatitis C
Version: 1 Date: 04 Dec 2020
Reviewer's report:
The study reports the association of two common steatogenic variants in the genes PNPLA3
and TM6SF2 with liver disease in 365 Brazilian patients with HCV, and 134 controls. Liver
disease was evaluated by histology. The main finding was that neither variant was associated
with increased steatosis or fibrosis in the cohort.
Comments
1. Please state in the abstract that steatosis and fibrosis were evaluated by histology.
2. It would be interesting to see associations for a combined risk score (PNPLA3 + TM6SF2).
3. How many had missing covariates? It seems from Table 1 that the dataset was almost
complete, with only a few missing information on some of the covaraites. Please add a statement
to this effect (ie. what was the max % of missing values for any covariate?) in the Methods
section.
4. the number of significant digits in numbers is excessive, throughout the manuscript (both
in the text and tables). Ie. percentages could be rounded to 1 digit after the period (instead of
30.49%, just use 30.5%), 'TM6SF2 and PNPLA3 heterozygosity were 0.1977 and 0.5608' should
be 0.20 and 0.56. P-values could be reported with 3 significant digits after the period. Ie. 0.044
instead of 0.0443. ORs should be with 2 digits after the period: '1.95, 95% CI 1.01-3.79' instead
of '1.9531 .953, 95% CI 1.009-3.788'.
5. The moderate sample size (and consequently low power) should be mentioned as a limitation.
6. The nucleotide position for the TM6SF2 variant is c.499C>T and not c.449 as stated
throughout. Please correct.
Minor
1. page 4 line 19: 'The wild allele (C allele)' , better: 'the common C allele'
2. Page 4, line 21: delete 'the' in front of TM6SF2.
3. page 13, line 13: 'PNPLA3 gene was not in Hardy-Weinberg equilibrium, what precludes firm
conclusions'. 'what' should be 'which'.
Please review this paper.
user
Title: The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic
abnormalities in Brazilian patients with chronic hepatitis C
Version: 1 Date: 04 Dec 2020
Reviewer's report:
The study reports the association of two common steatogenic variants in the genes PNPLA3
and TM6SF2 with liver disease in 365 Brazilian patients with HCV, and 134 controls. Liver
disease was evaluated by histology. The main finding was that neither variant was associated
with increased steatosis or fibrosis in the cohort.
Comments
1. Please state in the abstract that steatosis and fibrosis were evaluated by histology.
2. It would be interesting to see associations for a combined risk score (PNPLA3 + TM6SF2).
3. How many had missing covariates? It seems from Table 1 that the dataset was almost
complete, with only a few missing information on some of the covaraites. Please add a statement
to this effect (ie. what was the max % of missing values for any covariate?) in the Methods
section.
4. the number of significant digits in numbers is excessive, throughout the manuscript (both
in the text and tables). Ie. percentages could be rounded to 1 digit after the period (instead of
30.49%, just use 30.5%), 'TM6SF2 and PNPLA3 heterozygosity were 0.1977 and 0.5608' should
be 0.20 and 0.56. P-values could be reported with 3 significant digits after the period. Ie. 0.044
instead of 0.0443. ORs should be with 2 digits after the period: '1.95, 95% CI 1.01-3.79' instead
of '1.9531 .953, 95% CI 1.009-3.788'.
5. The moderate sample size (and consequently low power) should be mentioned as a limitation.
6. The nucleotide position for the TM6SF2 variant is c.499C>T and not c.449 as stated
throughout. Please correct.
Minor
1. page 4 line 19: 'The wild allele (C allele)' , better: 'the common C allele'
2. Page 4, line 21: delete 'the' in front of TM6SF2.
3. page 13, line 13: 'PNPLA3 gene was not in Hardy-Weinberg equilibrium, what precludes firm
conclusions'. 'what' should be 'which'.
assistant