Title: Effect of Factor VIII and FVIII/PC Ratio on Portal Vein Thrombosis in Liver Cirrhosis:
A Systematic Review and Meta#analysis
Version: 4 Date: 06 Aug 2024
Reviewer's report:
The manuscript  “Effect of factor VIII and FVIII/PC ratio on portal vein thrombosis in liver
cirrhosis: a systematic review and meta-analysis” reports the results of a systematic review
including  10 original studies that aim to elucidate the role of FVIII and FVIII/PC on the capacity
to predict portal vein thrombosis development.
The authors state that their result show that although FVIII alone does not correlate with the
presence of portal vein thrombosis the ratio FVIII/PC does show a potential to predict portal
vein thrombosis development.
However, there is a major concern in the methodology used. THe analysis performed evaluates
the difference in FVIII and FVIII/PC ratio levels between patients with and without PVT, but
importantly this does not necessarily imply causality. It is not clear if all the studies included
measured these coagulation factors at the same time (at the moment of PVT occurrence or much
earlier at the beggining of the disease? This is highly relevant to be able to conclude that FVIII/
PC ratio predicts PVT developent.
ALso, it would be very interesting if the authors could analyze if, as suggested by many of the
studies included in the metanalysis, FVIII and FVIII/PC ratio do not  correlate with the risk of
thrombosis but with the risk of hepatic decompensation or death. Indeed, this would be a very
important conclusion of the metanalysis.
Title: Effect of Factor VIII and FVIII/PC Ratio on Portal Vein Thrombosis in Liver Cirrhosis:
A Systematic Review and Meta#analysis
Version: 4 Date: 06 Aug 2024
Reviewer's report:
The manuscript  “Effect of factor VIII and FVIII/PC ratio on portal vein thrombosis in liver
cirrhosis: a systematic review and meta-analysis” reports the results of a systematic review
including  10 original studies that aim to elucidate the role of FVIII and FVIII/PC on the capacity
to predict portal vein thrombosis development.
The authors state that their result show that although FVIII alone does not correlate with the
presence of portal vein thrombosis the ratio FVIII/PC does show a potential to predict portal
vein thrombosis development.
However, there is a major concern in the methodology used. THe analysis performed evaluates
the difference in FVIII and FVIII/PC ratio levels between patients with and without PVT, but
importantly this does not necessarily imply causality. It is not clear if all the studies included
measured these coagulation factors at the same time (at the moment of PVT occurrence or much
earlier at the beggining of the disease? This is highly relevant to be able to conclude that FVIII/
PC ratio predicts PVT developent.
ALso, it would be very interesting if the authors could analyze if, as suggested by many of the
studies included in the metanalysis, FVIII and FVIII/PC ratio do not  correlate with the risk of
thrombosis but with the risk of hepatic decompensation or death. Indeed, this would be a very
important conclusion of the metanalysis.
Please review this paper.
user
Title: Effect of Factor VIII and FVIII/PC Ratio on Portal Vein Thrombosis in Liver Cirrhosis:
A Systematic Review and Meta#analysis
Version: 4 Date: 06 Aug 2024
Reviewer's report:
The manuscript  “Effect of factor VIII and FVIII/PC ratio on portal vein thrombosis in liver
cirrhosis: a systematic review and meta-analysis” reports the results of a systematic review
including  10 original studies that aim to elucidate the role of FVIII and FVIII/PC on the capacity
to predict portal vein thrombosis development.
The authors state that their result show that although FVIII alone does not correlate with the
presence of portal vein thrombosis the ratio FVIII/PC does show a potential to predict portal
vein thrombosis development.
However, there is a major concern in the methodology used. THe analysis performed evaluates
the difference in FVIII and FVIII/PC ratio levels between patients with and without PVT, but
importantly this does not necessarily imply causality. It is not clear if all the studies included
measured these coagulation factors at the same time (at the moment of PVT occurrence or much
earlier at the beggining of the disease? This is highly relevant to be able to conclude that FVIII/
PC ratio predicts PVT developent.
ALso, it would be very interesting if the authors could analyze if, as suggested by many of the
studies included in the metanalysis, FVIII and FVIII/PC ratio do not  correlate with the risk of
thrombosis but with the risk of hepatic decompensation or death. Indeed, this would be a very
important conclusion of the metanalysis.
assistant