Title: Correlation and Consistency Analysis between Various Indirect Portal Pressure Gradients
and Actual Portal Pressure Gradient
Version: 2 Date: 21 Jan 2025
Reviewer's report:
The manuscript reports data from a retrospective study comparing two different ways of
measuring the hepatic venous pressure gradient (HVPG): the first, the traditional one, by using
the free hepatic venous pressure (FHVP) as the outflow pressure (F-HVPG in the manuscript)
and the second by using the inferior vena cava pressure (IVCP) as the outflow pressure (I-
HVPG in the manuscript). Both HVPG were compared with the real portal pressure gradient
(PPG), the gold-standard to predict the clinical outcome of patients suffering from portal
hypertension, which was obtained during TIPS allocation. Authors found that the I-HVPG was
more representative of the PPG than the F-HVPG particularly for those patients with a difference
between the FHVP and IVCP>2mmHg (n=18 out of 112).
Several important criticisms may be raised against the manuscript and make the reproducibility
of the results not acceptable for such an important methodological aim and the final clinical
message. Authors can find a detailed report below.
MAJOR POINTS:
1. Patients with cholestatic liver disease should be excluded from the analysis. This should be
clearly stated in the methodology. Unfortunately, table 1 and what is declared in the discussion
apparently are not coherent. Indeed, in the discussion Authors wrote that 14.7% of etiologies of
the liver disease were not specified. This could influence the risk of having included patients
with cholestatic liver disease who, by definition, have a HVPG with does not correspond to the
PPG due to the pre-sinusoidal component not detected by the wedged hepatic venous pressure.
Along this line, recently it has been postulated a pre-sinusoidal component of portal pressure
associated with MASLD. Patients with this etiology on top of those declared in the manuscript,
should be identified and a sensitivity analysis by considering this confounding factor should be
added.
2. Paying attention to figure 2b, 4, 4b, it seems that some patients had HVPG and/or PPG
below 10 mmHg. This is something unexpected considering that all the patients were candidates
to TIPS for bleeding or ascites. This makes the reliability of the measurements technically
questionable.
3. As above, figure 2a shows that IVPC is higher than FHVP, which is not physiological. This,
again, makes the reliability of the measurements technically questionable. I understand that
retrospectively this cannot be adequately verified, but Authors can understand that this is a great
limitation for the study.
4. Was the IVCP used to calculate the I-HVPG the same used to calculate the PPG? Please, give
additional data on that.
5. Around 80% of the patients received TIPS for bleeding. Were all the measurements taken
while patients were under vasoactive drugs (e.g. terlipressin, somatostatin, octreotide) which
can influence the pressures? If so, this should be specified in the methodology.
6. Authors state in the discussion that IVCP is not influenced by the position of the catheter
used for the measurement. This is misleading since the level of measurement can gives different
results particularly in patients with cirrhosis who can have caudate liver lobe hypertrophy as
consequence of the advanced chronic liver disease.
7. Were authors able to revise the image retrospectively and specifying at which level of the
inferior cava vein the pressure was taken? In agreement with the comment above, this can
sensibly influence any hemodynamic measurement and should be specified.
MINOR POINTS
1. F-HVPG and I-HVPG should be in the abbreviation list
2. Authors could write cirrhosis instead of liver cirrhosis. There’s no other cirrhosis than that
of the liver
3. Authors should clearly state in the methodology section that the PPG is taken as reference
standard in tehir study to appreciate the reliability of the I-HVPG and F-HVPG
4. I suggest tagging group A and group B in the tables with their meaning, FHVP-
IVCP>2mmHg, FHVP-IVCP<=2mmHg, respectively.
5. The use of AUC to calculate the accuracy of I-HVPG and F-HVPG on measuring cut-offs
of PPG>16 mmHg and 20mmHg should be detailed in the methodology of the analysis. More,
in the result section, it should be detailed that the reference standard was the PPG for any cut-
off. In that section I also invite Authors to check before the level of agreement (Cohen's kappa
coefficient) between I-HVPG and F-HVPG for any cut-off.
6. It should be pointed out that the paper by Silva-junior challenged the I-HVPG against the
clinical end-point more than the PPG. Bya clinical point of view this is more important than the
simple agreement between PPG and I-HVPG and should be adequately discussed.
Title: Correlation and Consistency Analysis between Various Indirect Portal Pressure Gradients
and Actual Portal Pressure Gradient
Version: 2 Date: 21 Jan 2025
Reviewer's report:
The manuscript reports data from a retrospective study comparing two different ways of
measuring the hepatic venous pressure gradient (HVPG): the first, the traditional one, by using
the free hepatic venous pressure (FHVP) as the outflow pressure (F-HVPG in the manuscript)
and the second by using the inferior vena cava pressure (IVCP) as the outflow pressure (I-
HVPG in the manuscript). Both HVPG were compared with the real portal pressure gradient
(PPG), the gold-standard to predict the clinical outcome of patients suffering from portal
hypertension, which was obtained during TIPS allocation. Authors found that the I-HVPG was
more representative of the PPG than the F-HVPG particularly for those patients with a difference
between the FHVP and IVCP>2mmHg (n=18 out of 112).
Several important criticisms may be raised against the manuscript and make the reproducibility
of the results not acceptable for such an important methodological aim and the final clinical
message. Authors can find a detailed report below.
MAJOR POINTS:
1. Patients with cholestatic liver disease should be excluded from the analysis. This should be
clearly stated in the methodology. Unfortunately, table 1 and what is declared in the discussion
apparently are not coherent. Indeed, in the discussion Authors wrote that 14.7% of etiologies of
the liver disease were not specified. This could influence the risk of having included patients
with cholestatic liver disease who, by definition, have a HVPG with does not correspond to the
PPG due to the pre-sinusoidal component not detected by the wedged hepatic venous pressure.
Along this line, recently it has been postulated a pre-sinusoidal component of portal pressure
associated with MASLD. Patients with this etiology on top of those declared in the manuscript,
should be identified and a sensitivity analysis by considering this confounding factor should be
added.
2. Paying attention to figure 2b, 4, 4b, it seems that some patients had HVPG and/or PPG
below 10 mmHg. This is something unexpected considering that all the patients were candidates
to TIPS for bleeding or ascites. This makes the reliability of the measurements technically
questionable.
3. As above, figure 2a shows that IVPC is higher than FHVP, which is not physiological. This,
again, makes the reliability of the measurements technically questionable. I understand that
retrospectively this cannot be adequately verified, but Authors can understand that this is a great
limitation for the study.
4. Was the IVCP used to calculate the I-HVPG the same used to calculate the PPG? Please, give
additional data on that.
5. Around 80% of the patients received TIPS for bleeding. Were all the measurements taken
while patients were under vasoactive drugs (e.g. terlipressin, somatostatin, octreotide) which
can influence the pressures? If so, this should be specified in the methodology.
6. Authors state in the discussion that IVCP is not influenced by the position of the catheter
used for the measurement. This is misleading since the level of measurement can gives different
results particularly in patients with cirrhosis who can have caudate liver lobe hypertrophy as
consequence of the advanced chronic liver disease.
7. Were authors able to revise the image retrospectively and specifying at which level of the
inferior cava vein the pressure was taken? In agreement with the comment above, this can
sensibly influence any hemodynamic measurement and should be specified.
MINOR POINTS
1. F-HVPG and I-HVPG should be in the abbreviation list
2. Authors could write cirrhosis instead of liver cirrhosis. There’s no other cirrhosis than that
of the liver
3. Authors should clearly state in the methodology section that the PPG is taken as reference
standard in tehir study to appreciate the reliability of the I-HVPG and F-HVPG
4. I suggest tagging group A and group B in the tables with their meaning, FHVP-
IVCP>2mmHg, FHVP-IVCP<=2mmHg, respectively.
5. The use of AUC to calculate the accuracy of I-HVPG and F-HVPG on measuring cut-offs
of PPG>16 mmHg and 20mmHg should be detailed in the methodology of the analysis. More,
in the result section, it should be detailed that the reference standard was the PPG for any cut-
off. In that section I also invite Authors to check before the level of agreement (Cohen's kappa
coefficient) between I-HVPG and F-HVPG for any cut-off.
6. It should be pointed out that the paper by Silva-junior challenged the I-HVPG against the
clinical end-point more than the PPG. Bya clinical point of view this is more important than the
simple agreement between PPG and I-HVPG and should be adequately discussed.
Please review this paper.
user
Title: Correlation and Consistency Analysis between Various Indirect Portal Pressure Gradients
and Actual Portal Pressure Gradient
Version: 2 Date: 21 Jan 2025
Reviewer's report:
The manuscript reports data from a retrospective study comparing two different ways of
measuring the hepatic venous pressure gradient (HVPG): the first, the traditional one, by using
the free hepatic venous pressure (FHVP) as the outflow pressure (F-HVPG in the manuscript)
and the second by using the inferior vena cava pressure (IVCP) as the outflow pressure (I-
HVPG in the manuscript). Both HVPG were compared with the real portal pressure gradient
(PPG), the gold-standard to predict the clinical outcome of patients suffering from portal
hypertension, which was obtained during TIPS allocation. Authors found that the I-HVPG was
more representative of the PPG than the F-HVPG particularly for those patients with a difference
between the FHVP and IVCP>2mmHg (n=18 out of 112).
Several important criticisms may be raised against the manuscript and make the reproducibility
of the results not acceptable for such an important methodological aim and the final clinical
message. Authors can find a detailed report below.
MAJOR POINTS:
1. Patients with cholestatic liver disease should be excluded from the analysis. This should be
clearly stated in the methodology. Unfortunately, table 1 and what is declared in the discussion
apparently are not coherent. Indeed, in the discussion Authors wrote that 14.7% of etiologies of
the liver disease were not specified. This could influence the risk of having included patients
with cholestatic liver disease who, by definition, have a HVPG with does not correspond to the
PPG due to the pre-sinusoidal component not detected by the wedged hepatic venous pressure.
Along this line, recently it has been postulated a pre-sinusoidal component of portal pressure
associated with MASLD. Patients with this etiology on top of those declared in the manuscript,
should be identified and a sensitivity analysis by considering this confounding factor should be
added.
2. Paying attention to figure 2b, 4, 4b, it seems that some patients had HVPG and/or PPG
below 10 mmHg. This is something unexpected considering that all the patients were candidates
to TIPS for bleeding or ascites. This makes the reliability of the measurements technically
questionable.
3. As above, figure 2a shows that IVPC is higher than FHVP, which is not physiological. This,
again, makes the reliability of the measurements technically questionable. I understand that
retrospectively this cannot be adequately verified, but Authors can understand that this is a great
limitation for the study.
4. Was the IVCP used to calculate the I-HVPG the same used to calculate the PPG? Please, give
additional data on that.
5. Around 80% of the patients received TIPS for bleeding. Were all the measurements taken
while patients were under vasoactive drugs (e.g. terlipressin, somatostatin, octreotide) which
can influence the pressures? If so, this should be specified in the methodology.
6. Authors state in the discussion that IVCP is not influenced by the position of the catheter
used for the measurement. This is misleading since the level of measurement can gives different
results particularly in patients with cirrhosis who can have caudate liver lobe hypertrophy as
consequence of the advanced chronic liver disease.
7. Were authors able to revise the image retrospectively and specifying at which level of the
inferior cava vein the pressure was taken? In agreement with the comment above, this can
sensibly influence any hemodynamic measurement and should be specified.
MINOR POINTS
1. F-HVPG and I-HVPG should be in the abbreviation list
2. Authors could write cirrhosis instead of liver cirrhosis. There’s no other cirrhosis than that
of the liver
3. Authors should clearly state in the methodology section that the PPG is taken as reference
standard in tehir study to appreciate the reliability of the I-HVPG and F-HVPG
4. I suggest tagging group A and group B in the tables with their meaning, FHVP-
IVCP>2mmHg, FHVP-IVCP<=2mmHg, respectively.
5. The use of AUC to calculate the accuracy of I-HVPG and F-HVPG on measuring cut-offs
of PPG>16 mmHg and 20mmHg should be detailed in the methodology of the analysis. More,
in the result section, it should be detailed that the reference standard was the PPG for any cut-
off. In that section I also invite Authors to check before the level of agreement (Cohen's kappa
coefficient) between I-HVPG and F-HVPG for any cut-off.
6. It should be pointed out that the paper by Silva-junior challenged the I-HVPG against the
clinical end-point more than the PPG. Bya clinical point of view this is more important than the
simple agreement between PPG and I-HVPG and should be adequately discussed.
assistant