Reviewer's report
Title:Acute-on-chronic liver failure due to methimazole in a patient with
hyperthyroidism and trilogy of Fallot: case report
Version: 1Date:2 July 2010
Reviewer: M Isabel Lucena
Reviewer's report:
In this manuscript Shen and coworkers describe a case of acute-on-chronic liver
failure believed to be induced by methimazole in a patient with hyperthyroidism
and trilogy of Fallot. This is the first report of methimazole-induced acute liver
failure under the abovementioned medical conditions. The report is laid out
clearly and with detailed medical information. Although the authors provide
coherent evidence pointing towards methimazole as the main culprit in the case,
the patient’s underlying medical conditions should not be disregarded. This
manuscript would benefit from a more profound consideration of potential effects
of the underlying liver condition on the case development and outcome. This
case report conforms to ethical guidelines.
Suggestions for consideration and improvement of the manuscript are outlined
below:
Major considerations:
Title: The authors should use the drug name specified by the Anatomical
Therapeutic Chemical classification. Hence, methimazole should be referred to
as thiamazole (ATC code H03B002). The use of methimazole may be confused
with metamizole (N02BB02), an analgesics and antipyretics.
Page 3 (Background), first paragraph: The acronym ATDs is normally used for
antidepressant drugs. To avoid confusion it would be better if the authors
changed their acronym for antithyroid drugs, for example to ADs.
Page 3 (Background), first paragraph: “….. presenting with toxic hepatitis or
cholestatic jaundice…” is better referred to as “… presenting with hepatocelluar
or cholestatic injury…”
Page 3 (Background), last paragraph: “….. caused by MMI” is better written as
“….related to MMI”.
Page 4 (case report), first paragraph: The patient is said to have taken MMI for
one year intermittently without noticing any adverse effects. However, when MMI
was continuously administrated symptoms appeared after only two days. The
authors should comment on this. Did the daily dosage increase or remain the
same (20 mg/day) during the intermittent and continuous administrations? Was
any concomitant drugs (including non-ATDs) taken by the patient prior to hospital
admission? Was any over-the-counter drugs or herbal remedies, which may have
contributed to hepatotoxicity, taken by the patient?
Page 4 (case report), first paragraph: “There was no history of liver disease”.
What liver disease do the authors consider here?
Despite the lack of defined liver diseases the patient’s medical condition is known
to have the ability to cause liver dysfunctions, which may have affected his
susceptibility to hepatotoxicity. The authors should comment on this.
Page 4 (case report), third paragraph: The authors should include laboratory test
values for alkaline phosphatase (AP). The AST values could be removed. In
addition, inclusion of base line values would be preferable considering the
patient’s underlying liver condition. In addition, what do the authors mean with
“liver protecting preparations”? Those preparations should be specified and the
active ingredients listed.
Page 4 (case report), third paragraph: How was the lymphocyte stimulation test
for MMI performed?
Page 5 (case report), second paragraph: MMI was discontinued on admission
and treatment with PTU, propranolol and methylprednisolone was initiated. Could
this have had any effect on the progression and poor outcome of the case? The
authors should comment on this.
Page 6 (conclusions), second paragraph: The authors state “ only a small
proportion of patients can develop liver failure”. What do they mean with “small
proportion”?
Page 6 (conclusions), second paragraph: What do the authors mean with
“immune agents or idiosyncratic reactions”? Idiosyncratic drug-induced liver
injury can involve components of the immune system.
Page 6 (conclusions), second paragraph: It is important to state that the patient’s
condition was stable prior to drug treatment.
Page 6 (conclusions), second paragraph: The biopsy data are considered to
favour the MMI-induced liver injury. However, it only demonstrated cholestasis,
which is not specific for drug-induced injury. More specific biopsy findings, such
as eosinophils and centrolobulillar damage are needed to support drug-induced
injury.
Page 8 (conclusions), first paragraph: The authors have stated that “ATD was
proposed to be a risky approach due to the possibility of cross-reactivity between
the two agents”. Comments on the significance of this and possible effects on the
poor outcome should be given.
The report would benefit from inclusion of a CIOMS/RUCAM scale score.
Table 1: Converting the data in Table 1 into graph(s) could make the liver and
thyroid function test data more visual and subsequently facilitate the
comprehension of the progression of the various parameters during the time
period of hospitalization for the reader. Indications of when new drugs were
started would be beneficial, as well as baseline values and values for alkaline
phosphatase (AP)
Minor considerations:
Page 2 (abstract): The background sentence is grammatically confusing and
needs to be revised.
Page 2 (abstract): The first sentence in the case presentation section is
grammatically incorrect and should be “…….Fallot, who developed……” or
……”Fallot developing……”
Page 2 (abstract): The conclusions section is grammatically incorrect.
Suggestion for correction: “This case suggests that methimazole-induced
hepatotoxicity in the setting of advanced fibrosis increase (or can increase) the
risk of poor outcome. Regular liver function monitoring during methimazole
therapy is therefore important”
Page 3 (background), line 3: …..were widely…… should be …….are widely….
Page 3 (background), line 5: ……presenting with….. should be ….. presenting
as…..
Page 3 (background), line 14: This sentence reads better as: Here we report the
first case of a patient with hyperthyroidism and TOF that was recently referred to
our hospital for acute-on-chronic liver failure (ACLF) caused by MMI.
Page 6 (conclusions), line 2: ‘changes on liver histology’ should be ‘changes in
liver histology’
Page 6 (conclusions), line 12: ……’and only a small proportion of patients can
develop as liver failure’ is better worded as ….’but only a small proportion of
patients develop liver failure’ or ‘but only leads to liver failure in a small proportion
of patients’.
Page 6 (conclusions), line 14: in the English literature
Page 7 (conclusions), line 10: …’can lead to the liver damage’…. should be
…’can lead to liver damage’
Page 8 (conclusions), line 17: ….’enhance their awareness of that’…..
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'.
Reviewer's report
Title:Acute-on-chronic liver failure due to methimazole in a patient with
hyperthyroidism and trilogy of Fallot: case report
Version: 1Date:2 July 2010
Reviewer: M Isabel Lucena
Reviewer's report:
In this manuscript Shen and coworkers describe a case of acute-on-chronic liver
failure believed to be induced by methimazole in a patient with hyperthyroidism
and trilogy of Fallot. This is the first report of methimazole-induced acute liver
failure under the abovementioned medical conditions. The report is laid out
clearly and with detailed medical information. Although the authors provide
coherent evidence pointing towards methimazole as the main culprit in the case,
the patient’s underlying medical conditions should not be disregarded. This
manuscript would benefit from a more profound consideration of potential effects
of the underlying liver condition on the case development and outcome. This
case report conforms to ethical guidelines.
Suggestions for consideration and improvement of the manuscript are outlined
below:
Major considerations:
Title: The authors should use the drug name specified by the Anatomical
Therapeutic Chemical classification. Hence, methimazole should be referred to
as thiamazole (ATC code H03B002). The use of methimazole may be confused
with metamizole (N02BB02), an analgesics and antipyretics.
Page 3 (Background), first paragraph: The acronym ATDs is normally used for
antidepressant drugs. To avoid confusion it would be better if the authors
changed their acronym for antithyroid drugs, for example to ADs.
Page 3 (Background), first paragraph: “….. presenting with toxic hepatitis or
cholestatic jaundice…” is better referred to as “… presenting with hepatocelluar
or cholestatic injury…”
Page 3 (Background), last paragraph: “….. caused by MMI” is better written as
“….related to MMI”.
Page 4 (case report), first paragraph: The patient is said to have taken MMI for
one year intermittently without noticing any adverse effects. However, when MMI
was continuously administrated symptoms appeared after only two days. The
authors should comment on this. Did the daily dosage increase or remain the
same (20 mg/day) during the intermittent and continuous administrations? Was
any concomitant drugs (including non-ATDs) taken by the patient prior to hospital
admission? Was any over-the-counter drugs or herbal remedies, which may have
contributed to hepatotoxicity, taken by the patient?
Page 4 (case report), first paragraph: “There was no history of liver disease”.
What liver disease do the authors consider here?
Despite the lack of defined liver diseases the patient’s medical condition is known
to have the ability to cause liver dysfunctions, which may have affected his
susceptibility to hepatotoxicity. The authors should comment on this.
Page 4 (case report), third paragraph: The authors should include laboratory test
values for alkaline phosphatase (AP). The AST values could be removed. In
addition, inclusion of base line values would be preferable considering the
patient’s underlying liver condition. In addition, what do the authors mean with
“liver protecting preparations”? Those preparations should be specified and the
active ingredients listed.
Page 4 (case report), third paragraph: How was the lymphocyte stimulation test
for MMI performed?
Page 5 (case report), second paragraph: MMI was discontinued on admission
and treatment with PTU, propranolol and methylprednisolone was initiated. Could
this have had any effect on the progression and poor outcome of the case? The
authors should comment on this.
Page 6 (conclusions), second paragraph: The authors state “ only a small
proportion of patients can develop liver failure”. What do they mean with “small
proportion”?
Page 6 (conclusions), second paragraph: What do the authors mean with
“immune agents or idiosyncratic reactions”? Idiosyncratic drug-induced liver
injury can involve components of the immune system.
Page 6 (conclusions), second paragraph: It is important to state that the patient’s
condition was stable prior to drug treatment.
Page 6 (conclusions), second paragraph: The biopsy data are considered to
favour the MMI-induced liver injury. However, it only demonstrated cholestasis,
which is not specific for drug-induced injury. More specific biopsy findings, such
as eosinophils and centrolobulillar damage are needed to support drug-induced
injury.
Page 8 (conclusions), first paragraph: The authors have stated that “ATD was
proposed to be a risky approach due to the possibility of cross-reactivity between
the two agents”. Comments on the significance of this and possible effects on the
poor outcome should be given.
The report would benefit from inclusion of a CIOMS/RUCAM scale score.
Table 1: Converting the data in Table 1 into graph(s) could make the liver and
thyroid function test data more visual and subsequently facilitate the
comprehension of the progression of the various parameters during the time
period of hospitalization for the reader. Indications of when new drugs were
started would be beneficial, as well as baseline values and values for alkaline
phosphatase (AP)
Minor considerations:
Page 2 (abstract): The background sentence is grammatically confusing and
needs to be revised.
Page 2 (abstract): The first sentence in the case presentation section is
grammatically incorrect and should be “…….Fallot, who developed……” or
……”Fallot developing……”
Page 2 (abstract): The conclusions section is grammatically incorrect.
Suggestion for correction: “This case suggests that methimazole-induced
hepatotoxicity in the setting of advanced fibrosis increase (or can increase) the
risk of poor outcome. Regular liver function monitoring during methimazole
therapy is therefore important”
Page 3 (background), line 3: …..were widely…… should be …….are widely….
Page 3 (background), line 5: ……presenting with….. should be ….. presenting
as…..
Page 3 (background), line 14: This sentence reads better as: Here we report the
first case of a patient with hyperthyroidism and TOF that was recently referred to
our hospital for acute-on-chronic liver failure (ACLF) caused by MMI.
Page 6 (conclusions), line 2: ‘changes on liver histology’ should be ‘changes in
liver histology’
Page 6 (conclusions), line 12: ……’and only a small proportion of patients can
develop as liver failure’ is better worded as ….’but only a small proportion of
patients develop liver failure’ or ‘but only leads to liver failure in a small proportion
of patients’.
Page 6 (conclusions), line 14: in the English literature
Page 7 (conclusions), line 10: …’can lead to the liver damage’…. should be
…’can lead to liver damage’
Page 8 (conclusions), line 17: ….’enhance their awareness of that’…..
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'.
Please review this paper.
user
Reviewer's report
Title:Acute-on-chronic liver failure due to methimazole in a patient with
hyperthyroidism and trilogy of Fallot: case report
Version: 1Date:2 July 2010
Reviewer: M Isabel Lucena
Reviewer's report:
In this manuscript Shen and coworkers describe a case of acute-on-chronic liver
failure believed to be induced by methimazole in a patient with hyperthyroidism
and trilogy of Fallot. This is the first report of methimazole-induced acute liver
failure under the abovementioned medical conditions. The report is laid out
clearly and with detailed medical information. Although the authors provide
coherent evidence pointing towards methimazole as the main culprit in the case,
the patient’s underlying medical conditions should not be disregarded. This
manuscript would benefit from a more profound consideration of potential effects
of the underlying liver condition on the case development and outcome. This
case report conforms to ethical guidelines.
Suggestions for consideration and improvement of the manuscript are outlined
below:
Major considerations:
Title: The authors should use the drug name specified by the Anatomical
Therapeutic Chemical classification. Hence, methimazole should be referred to
as thiamazole (ATC code H03B002). The use of methimazole may be confused
with metamizole (N02BB02), an analgesics and antipyretics.
Page 3 (Background), first paragraph: The acronym ATDs is normally used for
antidepressant drugs. To avoid confusion it would be better if the authors
changed their acronym for antithyroid drugs, for example to ADs.
Page 3 (Background), first paragraph: “….. presenting with toxic hepatitis or
cholestatic jaundice…” is better referred to as “… presenting with hepatocelluar
or cholestatic injury…”
Page 3 (Background), last paragraph: “….. caused by MMI” is better written as
“….related to MMI”.
Page 4 (case report), first paragraph: The patient is said to have taken MMI for
one year intermittently without noticing any adverse effects. However, when MMI
was continuously administrated symptoms appeared after only two days. The
authors should comment on this. Did the daily dosage increase or remain the
same (20 mg/day) during the intermittent and continuous administrations? Was
any concomitant drugs (including non-ATDs) taken by the patient prior to hospital
admission? Was any over-the-counter drugs or herbal remedies, which may have
contributed to hepatotoxicity, taken by the patient?
Page 4 (case report), first paragraph: “There was no history of liver disease”.
What liver disease do the authors consider here?
Despite the lack of defined liver diseases the patient’s medical condition is known
to have the ability to cause liver dysfunctions, which may have affected his
susceptibility to hepatotoxicity. The authors should comment on this.
Page 4 (case report), third paragraph: The authors should include laboratory test
values for alkaline phosphatase (AP). The AST values could be removed. In
addition, inclusion of base line values would be preferable considering the
patient’s underlying liver condition. In addition, what do the authors mean with
“liver protecting preparations”? Those preparations should be specified and the
active ingredients listed.
Page 4 (case report), third paragraph: How was the lymphocyte stimulation test
for MMI performed?
Page 5 (case report), second paragraph: MMI was discontinued on admission
and treatment with PTU, propranolol and methylprednisolone was initiated. Could
this have had any effect on the progression and poor outcome of the case? The
authors should comment on this.
Page 6 (conclusions), second paragraph: The authors state “ only a small
proportion of patients can develop liver failure”. What do they mean with “small
proportion”?
Page 6 (conclusions), second paragraph: What do the authors mean with
“immune agents or idiosyncratic reactions”? Idiosyncratic drug-induced liver
injury can involve components of the immune system.
Page 6 (conclusions), second paragraph: It is important to state that the patient’s
condition was stable prior to drug treatment.
Page 6 (conclusions), second paragraph: The biopsy data are considered to
favour the MMI-induced liver injury. However, it only demonstrated cholestasis,
which is not specific for drug-induced injury. More specific biopsy findings, such
as eosinophils and centrolobulillar damage are needed to support drug-induced
injury.
Page 8 (conclusions), first paragraph: The authors have stated that “ATD was
proposed to be a risky approach due to the possibility of cross-reactivity between
the two agents”. Comments on the significance of this and possible effects on the
poor outcome should be given.
The report would benefit from inclusion of a CIOMS/RUCAM scale score.
Table 1: Converting the data in Table 1 into graph(s) could make the liver and
thyroid function test data more visual and subsequently facilitate the
comprehension of the progression of the various parameters during the time
period of hospitalization for the reader. Indications of when new drugs were
started would be beneficial, as well as baseline values and values for alkaline
phosphatase (AP)
Minor considerations:
Page 2 (abstract): The background sentence is grammatically confusing and
needs to be revised.
Page 2 (abstract): The first sentence in the case presentation section is
grammatically incorrect and should be “…….Fallot, who developed……” or
……”Fallot developing……”
Page 2 (abstract): The conclusions section is grammatically incorrect.
Suggestion for correction: “This case suggests that methimazole-induced
hepatotoxicity in the setting of advanced fibrosis increase (or can increase) the
risk of poor outcome. Regular liver function monitoring during methimazole
therapy is therefore important”
Page 3 (background), line 3: …..were widely…… should be …….are widely….
Page 3 (background), line 5: ……presenting with….. should be ….. presenting
as…..
Page 3 (background), line 14: This sentence reads better as: Here we report the
first case of a patient with hyperthyroidism and TOF that was recently referred to
our hospital for acute-on-chronic liver failure (ACLF) caused by MMI.
Page 6 (conclusions), line 2: ‘changes on liver histology’ should be ‘changes in
liver histology’
Page 6 (conclusions), line 12: ……’and only a small proportion of patients can
develop as liver failure’ is better worded as ….’but only a small proportion of
patients develop liver failure’ or ‘but only leads to liver failure in a small proportion
of patients’.
Page 6 (conclusions), line 14: in the English literature
Page 7 (conclusions), line 10: …’can lead to the liver damage’…. should be
…’can lead to liver damage’
Page 8 (conclusions), line 17: ….’enhance their awareness of that’…..
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'.
assistant