Title: The longterm impact of post-cholecystectomy major bile duct injury on liver stiffness.
Version: 5 Date: 23 Sep 2024
Reviewer:  Keita Shimata
Reviewer's report:
The authors conducted a prospective cohort study on the impact of post-cholecystectomy major
BDI on liver stiffness and asserted that uncomplicated BDI repair did not result in liver fibrosis
and that the coexistence of hepatic artery injury was a risk factor for liver fibrosis. A strength
of this study is that the BDI cases were evaluated for liver fibrosis after more than 6 months.
Although this study is of interest, several concerns need to be addressed. Please find below
specific comments.
Abstract:
1. Please add the study period and the number of participants in the control group. (Line 33)
2. It says, "Liver fibrosis was assessed using the METAVIR scoring system," but since no
liver biopsy was performed, please state more accurately, "Replace the Fibroscan value with
METAVIR." (Line 36-37)
3. Although it is stated that "Fibrosis assessment revealed comparable distribution between the
study and control groups," there was a significant difference in the F3/4 ratio between the two
groups, and the content of the statement is different from the results. Please express it more
accurately. (Line 42-44)
4. There was no statistically significant difference in biliary jejunostomy stricture, so it should
not be stated that there was an association with fibrosis. (Line 45)
5. The conclusion statement is inconsistent with the research results. Please state it accurately.
(See the review comments for the conclusion.)
Methods:
1. When evaluating liver fibrosis, a 6-month period seems insufficient to assess long-term
progression. If you have a reason for six months or more, please provide it.
2. In this study, one patient with cirrhosis was excluded. Has it been confirmed that the other 19
patients and the control group did not have liver disease that could cause fibrosis? (Line 86)
3. Please provide details on how the control group was selected. Was it a group of post-
cholesteatoma patients who did not have bile duct injury? (Line 87)
4. Please specify when the blood test was performed. (Line 105)
Result:
1. Because Fib-4 analysis is a predictive formula, results should be reported numerically, and a
cut-off value for determining advanced fibrosis should be provided. (Line 140-141)
2. In cases where fibrosis had progressed after re-anastomosis of the HJ, did the anastomotic
stricture improve? How long did the stricture last? Please write this down if possible, as it is
related to fibrosis. (Line 149-152)
3. Does "artery injury" mean a blockage of blood flow? Please provide a detailed description
of the artery injury. (Line 151)
4. In Table 1, if a liver biopsy was not performed, using the METAVIR system seems incorrect.
It would be better to list the liver stiffness measurement value as a range and the score equivalent
to the METAVIR system.
5. The explanation in the text about the univariate analysis in Table 2 is insufficient. Please
include the results of the analysis in the text. (Line 152)
6. In Table 2, “absent of hepatic artery injury,” “absent anastomotic stricture,” “absent of
cholangitis,” and “non diabetic,” and “BMI below 25” are unnecessary.
7. Were there any differences between the results of Fib-4 analysis and Fibroscan? This paper
mainly focuses on the fibrosis evaluation, so this should be stated.
Discussion:
1. The advantages of Fibroscan have been described. Please also describe its limitations. (Line
192-192)
2. This study only evaluated fibrosis, so the statement "This indicates that a successful repair
without risk factors can lead to near-complete recovery" is an overstatement. Please rewrite it
into an appropriate expression. (Line224-225)
3. Do “patients at higher risk” mean those with hepatic artery injury and those with bile duct
stenosis? It would be easier to understand if you specified that. (Line 226)
4. The author says that closed monitoring is necessary, but what kind of intervention do you
envision with early detection? If hepatic artery injury or bile duct stenosis is the cause of the
progression of fibrosis, I think therapeutic intervention for those factors would precede the
progression of fibrosis. (Line 226)
5. There is no description of limitations. I think there are limitations to this study, such as the
small number of participants, the lack of liver biopsy results, and whether the subject group is
eligible as a control. Please describe them.
Conclusion:
1. Since there is a statistical difference between the F3/4 fibrosis rates in the BDI and control
groups, it is incorrect to say that the two groups are equivalent. Please express it accurately based
on the results of this study.
Title: The longterm impact of post-cholecystectomy major bile duct injury on liver stiffness.
Version: 5 Date: 23 Sep 2024
Reviewer:  Keita Shimata
Reviewer's report:
The authors conducted a prospective cohort study on the impact of post-cholecystectomy major
BDI on liver stiffness and asserted that uncomplicated BDI repair did not result in liver fibrosis
and that the coexistence of hepatic artery injury was a risk factor for liver fibrosis. A strength
of this study is that the BDI cases were evaluated for liver fibrosis after more than 6 months.
Although this study is of interest, several concerns need to be addressed. Please find below
specific comments.
Abstract:
1. Please add the study period and the number of participants in the control group. (Line 33)
2. It says, "Liver fibrosis was assessed using the METAVIR scoring system," but since no
liver biopsy was performed, please state more accurately, "Replace the Fibroscan value with
METAVIR." (Line 36-37)
3. Although it is stated that "Fibrosis assessment revealed comparable distribution between the
study and control groups," there was a significant difference in the F3/4 ratio between the two
groups, and the content of the statement is different from the results. Please express it more
accurately. (Line 42-44)
4. There was no statistically significant difference in biliary jejunostomy stricture, so it should
not be stated that there was an association with fibrosis. (Line 45)
5. The conclusion statement is inconsistent with the research results. Please state it accurately.
(See the review comments for the conclusion.)
Methods:
1. When evaluating liver fibrosis, a 6-month period seems insufficient to assess long-term
progression. If you have a reason for six months or more, please provide it.
2. In this study, one patient with cirrhosis was excluded. Has it been confirmed that the other 19
patients and the control group did not have liver disease that could cause fibrosis? (Line 86)
3. Please provide details on how the control group was selected. Was it a group of post-
cholesteatoma patients who did not have bile duct injury? (Line 87)
4. Please specify when the blood test was performed. (Line 105)
Result:
1. Because Fib-4 analysis is a predictive formula, results should be reported numerically, and a
cut-off value for determining advanced fibrosis should be provided. (Line 140-141)
2. In cases where fibrosis had progressed after re-anastomosis of the HJ, did the anastomotic
stricture improve? How long did the stricture last? Please write this down if possible, as it is
related to fibrosis. (Line 149-152)
3. Does "artery injury" mean a blockage of blood flow? Please provide a detailed description
of the artery injury. (Line 151)
4. In Table 1, if a liver biopsy was not performed, using the METAVIR system seems incorrect.
It would be better to list the liver stiffness measurement value as a range and the score equivalent
to the METAVIR system.
5. The explanation in the text about the univariate analysis in Table 2 is insufficient. Please
include the results of the analysis in the text. (Line 152)
6. In Table 2, “absent of hepatic artery injury,” “absent anastomotic stricture,” “absent of
cholangitis,” and “non diabetic,” and “BMI below 25” are unnecessary.
7. Were there any differences between the results of Fib-4 analysis and Fibroscan? This paper
mainly focuses on the fibrosis evaluation, so this should be stated.
Discussion:
1. The advantages of Fibroscan have been described. Please also describe its limitations. (Line
192-192)
2. This study only evaluated fibrosis, so the statement "This indicates that a successful repair
without risk factors can lead to near-complete recovery" is an overstatement. Please rewrite it
into an appropriate expression. (Line224-225)
3. Do “patients at higher risk” mean those with hepatic artery injury and those with bile duct
stenosis? It would be easier to understand if you specified that. (Line 226)
4. The author says that closed monitoring is necessary, but what kind of intervention do you
envision with early detection? If hepatic artery injury or bile duct stenosis is the cause of the
progression of fibrosis, I think therapeutic intervention for those factors would precede the
progression of fibrosis. (Line 226)
5. There is no description of limitations. I think there are limitations to this study, such as the
small number of participants, the lack of liver biopsy results, and whether the subject group is
eligible as a control. Please describe them.
Conclusion:
1. Since there is a statistical difference between the F3/4 fibrosis rates in the BDI and control
groups, it is incorrect to say that the two groups are equivalent. Please express it accurately based
on the results of this study.
Please review this paper.
user
Title: The longterm impact of post-cholecystectomy major bile duct injury on liver stiffness.
Version: 5 Date: 23 Sep 2024
Reviewer:  Keita Shimata
Reviewer's report:
The authors conducted a prospective cohort study on the impact of post-cholecystectomy major
BDI on liver stiffness and asserted that uncomplicated BDI repair did not result in liver fibrosis
and that the coexistence of hepatic artery injury was a risk factor for liver fibrosis. A strength
of this study is that the BDI cases were evaluated for liver fibrosis after more than 6 months.
Although this study is of interest, several concerns need to be addressed. Please find below
specific comments.
Abstract:
1. Please add the study period and the number of participants in the control group. (Line 33)
2. It says, "Liver fibrosis was assessed using the METAVIR scoring system," but since no
liver biopsy was performed, please state more accurately, "Replace the Fibroscan value with
METAVIR." (Line 36-37)
3. Although it is stated that "Fibrosis assessment revealed comparable distribution between the
study and control groups," there was a significant difference in the F3/4 ratio between the two
groups, and the content of the statement is different from the results. Please express it more
accurately. (Line 42-44)
4. There was no statistically significant difference in biliary jejunostomy stricture, so it should
not be stated that there was an association with fibrosis. (Line 45)
5. The conclusion statement is inconsistent with the research results. Please state it accurately.
(See the review comments for the conclusion.)
Methods:
1. When evaluating liver fibrosis, a 6-month period seems insufficient to assess long-term
progression. If you have a reason for six months or more, please provide it.
2. In this study, one patient with cirrhosis was excluded. Has it been confirmed that the other 19
patients and the control group did not have liver disease that could cause fibrosis? (Line 86)
3. Please provide details on how the control group was selected. Was it a group of post-
cholesteatoma patients who did not have bile duct injury? (Line 87)
4. Please specify when the blood test was performed. (Line 105)
Result:
1. Because Fib-4 analysis is a predictive formula, results should be reported numerically, and a
cut-off value for determining advanced fibrosis should be provided. (Line 140-141)
2. In cases where fibrosis had progressed after re-anastomosis of the HJ, did the anastomotic
stricture improve? How long did the stricture last? Please write this down if possible, as it is
related to fibrosis. (Line 149-152)
3. Does "artery injury" mean a blockage of blood flow? Please provide a detailed description
of the artery injury. (Line 151)
4. In Table 1, if a liver biopsy was not performed, using the METAVIR system seems incorrect.
It would be better to list the liver stiffness measurement value as a range and the score equivalent
to the METAVIR system.
5. The explanation in the text about the univariate analysis in Table 2 is insufficient. Please
include the results of the analysis in the text. (Line 152)
6. In Table 2, “absent of hepatic artery injury,” “absent anastomotic stricture,” “absent of
cholangitis,” and “non diabetic,” and “BMI below 25” are unnecessary.
7. Were there any differences between the results of Fib-4 analysis and Fibroscan? This paper
mainly focuses on the fibrosis evaluation, so this should be stated.
Discussion:
1. The advantages of Fibroscan have been described. Please also describe its limitations. (Line
192-192)
2. This study only evaluated fibrosis, so the statement "This indicates that a successful repair
without risk factors can lead to near-complete recovery" is an overstatement. Please rewrite it
into an appropriate expression. (Line224-225)
3. Do “patients at higher risk” mean those with hepatic artery injury and those with bile duct
stenosis? It would be easier to understand if you specified that. (Line 226)
4. The author says that closed monitoring is necessary, but what kind of intervention do you
envision with early detection? If hepatic artery injury or bile duct stenosis is the cause of the
progression of fibrosis, I think therapeutic intervention for those factors would precede the
progression of fibrosis. (Line 226)
5. There is no description of limitations. I think there are limitations to this study, such as the
small number of participants, the lack of liver biopsy results, and whether the subject group is
eligible as a control. Please describe them.
Conclusion:
1. Since there is a statistical difference between the F3/4 fibrosis rates in the BDI and control
groups, it is incorrect to say that the two groups are equivalent. Please express it accurately based
on the results of this study.
assistant