Title: ROLE OF PERCUTANEOUS LIVER BIOPSY IN INFANTILE CHOLESTASIS:
COHORT FROM ARABS
Version: 1 Date: 24 Nov 2020
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study is an interesting report to investigate the role of liver biopsy in infants with cholestasis
from the largest tertiary hospital in Saudi Arabia. While this is a valuable report of a relatively
large number of cases from the Arab world, its content is not novel. Deeper consideration will
be required for publication in this journal.
This article is well-written and the topic is of great significance given the recent reports on this
topic in the literature. The figures and tables add greatly to the manuscripts. Again, there is
value in this report. However, there is nothing new in this discussion section. Previous reports
including pathology results are similar and should be considered from a different perspective.
[Major points]
1. Please refine the discussion section. The information obtained from this observational study
is not novel from previous reports of biliary atresia (BA). The pathology results were also
consistent with and similar to textbook descriptions. However, this study was still very valuable
as a report from the largest Arab institution and should be reconsidered in a deeper perspective.
For example, with the rise of molecular and gene tests, the significance of liver biopsy has
decreased, but its value is still there, especially as a differential diagnosis of BA. However, the
results of this study indicated that the time to perform a liver biopsy was very late. This may
lead to the delay of Kasai procedure, increase the liver transplantation, and eventually lead to a
worse prognosis. The authors should add to the consideration of that late timing for liver biopsy
and whether or not to introduce screening that could improve it.
2. Could you please explain the high rate of insufficient interpretational specimens in
the Discussion section? It is surprising that among the liver biopsies performed, 32/166
(approximately 20%) of liver biopsies were failed.
3. In the Discussion section, the authors discussed the significance of diagnosing biliary atresia
(BA) within 8 weeks. However, as shown in table 1, the average time of liver biopsy in the BA
group was about 11 weeks. In the non-BA group, the average time to biopsy was 20 weeks,
which was too late if liver biopsy was used as an exclusionary diagnosis of BA. This late timing
of liver biopsy should be considered.
4. In Discussion section (p18, lines 326-327), the authors stated that there was no reliable
noninvasive maker to distinguish between BA and other infantile cholestasis. Nowadays,
MMP-7 could be a good non-invasive tool for the diagnosis of BA. Could you please add the
perspectives of MMP-7 in the Discussion section?
(Yang L, et al. Diagnostic Accuracy of Serum Matrix Metalloproteinase#7 for Biliary Atresia.
Hepatology 2018; 68: 2069-2077.)
5. In the Discussion section, the authors mentioned that the positive predictive value (diagnostic
accuracy) in this BA seemed to be relatively low. The authors mentioned that the results were
similar to those of the ChiLDReN study by Russo p et al, however did this take-into-account
the timing of the liver biopsy? In this study, the liver biopsy time was late and therefore the
diagnostic accuracy should be higher.
[Minor points]
1. In Abstract (P3, line 33), please replace “Therefore;” with “Therefore,”.
2. In Abstract (p3, lines 36, 37, 41, 43, 44, 46, 50), please use the abbreviation “IC” which the
authors defined.
3. In Abstract (p3, lines 36), please use the abbreviation “IC” which the authors defined.
4. In Abstract (p3, lines 36), please use the abbreviation “LB” which the authors defined. Or, do
not set up the abbreviation of liver biopsy in the first paragraph.
5. In Abstract (p3, lines 45-46), please use the abbreviation “BA” which the authors defined.
Or, do not set up the abbreviation of biliary atresia as BA.
6. In Introduction (p5, line 76), the statistical term “prevalence rate” would not be appropriate
in this case.
7. In Introduction (p6, line 93), please set up the abbreviation of IC in the main manuscript when
it is first used.
8. In Reference (P25, lines 486-488), #14 paper was not published from Pediatrics, but BMC
Pediatrics.
Title: ROLE OF PERCUTANEOUS LIVER BIOPSY IN INFANTILE CHOLESTASIS:
COHORT FROM ARABS
Version: 1 Date: 24 Nov 2020
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study is an interesting report to investigate the role of liver biopsy in infants with cholestasis
from the largest tertiary hospital in Saudi Arabia. While this is a valuable report of a relatively
large number of cases from the Arab world, its content is not novel. Deeper consideration will
be required for publication in this journal.
This article is well-written and the topic is of great significance given the recent reports on this
topic in the literature. The figures and tables add greatly to the manuscripts. Again, there is
value in this report. However, there is nothing new in this discussion section. Previous reports
including pathology results are similar and should be considered from a different perspective.
[Major points]
1. Please refine the discussion section. The information obtained from this observational study
is not novel from previous reports of biliary atresia (BA). The pathology results were also
consistent with and similar to textbook descriptions. However, this study was still very valuable
as a report from the largest Arab institution and should be reconsidered in a deeper perspective.
For example, with the rise of molecular and gene tests, the significance of liver biopsy has
decreased, but its value is still there, especially as a differential diagnosis of BA. However, the
results of this study indicated that the time to perform a liver biopsy was very late. This may
lead to the delay of Kasai procedure, increase the liver transplantation, and eventually lead to a
worse prognosis. The authors should add to the consideration of that late timing for liver biopsy
and whether or not to introduce screening that could improve it.
2. Could you please explain the high rate of insufficient interpretational specimens in
the Discussion section? It is surprising that among the liver biopsies performed, 32/166
(approximately 20%) of liver biopsies were failed.
3. In the Discussion section, the authors discussed the significance of diagnosing biliary atresia
(BA) within 8 weeks. However, as shown in table 1, the average time of liver biopsy in the BA
group was about 11 weeks. In the non-BA group, the average time to biopsy was 20 weeks,
which was too late if liver biopsy was used as an exclusionary diagnosis of BA. This late timing
of liver biopsy should be considered.
4. In Discussion section (p18, lines 326-327), the authors stated that there was no reliable
noninvasive maker to distinguish between BA and other infantile cholestasis. Nowadays,
MMP-7 could be a good non-invasive tool for the diagnosis of BA. Could you please add the
perspectives of MMP-7 in the Discussion section?
(Yang L, et al. Diagnostic Accuracy of Serum Matrix Metalloproteinase#7 for Biliary Atresia.
Hepatology 2018; 68: 2069-2077.)
5. In the Discussion section, the authors mentioned that the positive predictive value (diagnostic
accuracy) in this BA seemed to be relatively low. The authors mentioned that the results were
similar to those of the ChiLDReN study by Russo p et al, however did this take-into-account
the timing of the liver biopsy? In this study, the liver biopsy time was late and therefore the
diagnostic accuracy should be higher.
[Minor points]
1. In Abstract (P3, line 33), please replace “Therefore;” with “Therefore,”.
2. In Abstract (p3, lines 36, 37, 41, 43, 44, 46, 50), please use the abbreviation “IC” which the
authors defined.
3. In Abstract (p3, lines 36), please use the abbreviation “IC” which the authors defined.
4. In Abstract (p3, lines 36), please use the abbreviation “LB” which the authors defined. Or, do
not set up the abbreviation of liver biopsy in the first paragraph.
5. In Abstract (p3, lines 45-46), please use the abbreviation “BA” which the authors defined.
Or, do not set up the abbreviation of biliary atresia as BA.
6. In Introduction (p5, line 76), the statistical term “prevalence rate” would not be appropriate
in this case.
7. In Introduction (p6, line 93), please set up the abbreviation of IC in the main manuscript when
it is first used.
8. In Reference (P25, lines 486-488), #14 paper was not published from Pediatrics, but BMC
Pediatrics.
Please review this paper.
user
Title: ROLE OF PERCUTANEOUS LIVER BIOPSY IN INFANTILE CHOLESTASIS:
COHORT FROM ARABS
Version: 1 Date: 24 Nov 2020
Reviewer:  Toshifumi Yodoshi
Reviewer's report:
This study is an interesting report to investigate the role of liver biopsy in infants with cholestasis
from the largest tertiary hospital in Saudi Arabia. While this is a valuable report of a relatively
large number of cases from the Arab world, its content is not novel. Deeper consideration will
be required for publication in this journal.
This article is well-written and the topic is of great significance given the recent reports on this
topic in the literature. The figures and tables add greatly to the manuscripts. Again, there is
value in this report. However, there is nothing new in this discussion section. Previous reports
including pathology results are similar and should be considered from a different perspective.
[Major points]
1. Please refine the discussion section. The information obtained from this observational study
is not novel from previous reports of biliary atresia (BA). The pathology results were also
consistent with and similar to textbook descriptions. However, this study was still very valuable
as a report from the largest Arab institution and should be reconsidered in a deeper perspective.
For example, with the rise of molecular and gene tests, the significance of liver biopsy has
decreased, but its value is still there, especially as a differential diagnosis of BA. However, the
results of this study indicated that the time to perform a liver biopsy was very late. This may
lead to the delay of Kasai procedure, increase the liver transplantation, and eventually lead to a
worse prognosis. The authors should add to the consideration of that late timing for liver biopsy
and whether or not to introduce screening that could improve it.
2. Could you please explain the high rate of insufficient interpretational specimens in
the Discussion section? It is surprising that among the liver biopsies performed, 32/166
(approximately 20%) of liver biopsies were failed.
3. In the Discussion section, the authors discussed the significance of diagnosing biliary atresia
(BA) within 8 weeks. However, as shown in table 1, the average time of liver biopsy in the BA
group was about 11 weeks. In the non-BA group, the average time to biopsy was 20 weeks,
which was too late if liver biopsy was used as an exclusionary diagnosis of BA. This late timing
of liver biopsy should be considered.
4. In Discussion section (p18, lines 326-327), the authors stated that there was no reliable
noninvasive maker to distinguish between BA and other infantile cholestasis. Nowadays,
MMP-7 could be a good non-invasive tool for the diagnosis of BA. Could you please add the
perspectives of MMP-7 in the Discussion section?
(Yang L, et al. Diagnostic Accuracy of Serum Matrix Metalloproteinase#7 for Biliary Atresia.
Hepatology 2018; 68: 2069-2077.)
5. In the Discussion section, the authors mentioned that the positive predictive value (diagnostic
accuracy) in this BA seemed to be relatively low. The authors mentioned that the results were
similar to those of the ChiLDReN study by Russo p et al, however did this take-into-account
the timing of the liver biopsy? In this study, the liver biopsy time was late and therefore the
diagnostic accuracy should be higher.
[Minor points]
1. In Abstract (P3, line 33), please replace “Therefore;” with “Therefore,”.
2. In Abstract (p3, lines 36, 37, 41, 43, 44, 46, 50), please use the abbreviation “IC” which the
authors defined.
3. In Abstract (p3, lines 36), please use the abbreviation “IC” which the authors defined.
4. In Abstract (p3, lines 36), please use the abbreviation “LB” which the authors defined. Or, do
not set up the abbreviation of liver biopsy in the first paragraph.
5. In Abstract (p3, lines 45-46), please use the abbreviation “BA” which the authors defined.
Or, do not set up the abbreviation of biliary atresia as BA.
6. In Introduction (p5, line 76), the statistical term “prevalence rate” would not be appropriate
in this case.
7. In Introduction (p6, line 93), please set up the abbreviation of IC in the main manuscript when
it is first used.
8. In Reference (P25, lines 486-488), #14 paper was not published from Pediatrics, but BMC
Pediatrics.
assistant