Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 1Date:12 August 2011
Reviewer: Debbie Shawcross
Reviewer's report:
This study describes an exploration of the role of capillary blood ammonia
estimation in conjunction with a 20 gram oral glutamine challenge (OGC) in 57
patients with advanced cirrhosis with and without a prior history of overt hepatic
encephalopathy (HE). The authors conclude that by itself, capillary blood
ammonia is not a good biomarker of minimal HE and does not reliably predict
future episodes of HE. However, use of the OGC with capillary blood ammonia
estimation improves the diagnostic yield of minimal HE from 44% to 67%.
The notion that isolated blood ammonia level (whether venous or arterial) are
poor predictors of minimal or overt HE has been well established in the literature
by several groups and baseline systemic inflammation has been shown to have
some influence on the cerebral effects of ammonia, in minimal HE using an
amino acid challenge [Shawcross DL, Wright G, Olde Damink SWM and Jalan R.
Role of Ammonia and Inflammation in Minimal Hepatic Encephalopathy.
Metabolic Brain Disease 2007; 22(1):125-38].
The novelty of this study therefore lays in the proposition that OGC and capillary
blood ammonia estimation may be utilised as a point of care diagnostic test for
minimal HE (AUROC 0.727) in patients with cirrhosis. Nevertheless, the time
taken to perform the OGC and 2 sets of neuropsychometry must still have taken
a minimum of 2 hours which may not be feasible to do in all patients presenting
with moderate or advanced cirrhosis.
- Major Compulsory Revisions
1. The authors state that healthy controls were enrolled (Figure 2) and a subset
of patients who had ammonia levels determined simultaneously in 2 vascular
beds (Figure 3). How many controls were used and did they also have
neuropsychomtery performed as well as capillary ammonia? These data need to
be added to the manuscript, table 2 and figure 2. How many patients had 2
vascular beds examined and were they part of the n=57 patients with cirrhosis?
These data need to be added to Figure 3 and discussed in a little more detail in
the manuscript body.
2. The numbers of patients stated to have minimal HE at baseline varies from
45% in the abstract, to 48% in the results and discussion. I calculate 25/57 with
baseline HE to be 44%. Please amend throughout manuscript.
3. The same applies to patients diagnosed with HE post OGC. The abstract says
69% and the results say 67%. I make 38/57 to be 67%. Please amend.
4. This therefore makes me wary that there are other mathematical errors in the
numbers and statistics throughout the manuscript. Please re-check throroughly.
5. It is contentious to give an amino acid challenge to a patient with TIPSS who is
at high risk of developing overt HE as the glutamine will largely bypass the liver.
Previous studies using amino acid challenge and OGC have largely excluded
TIPSS patients. Furthermore, many patients with TIPSS have evidence of
minimal HE at baseline. Please explain the reasoning behind their inclusion and
detail the presence or absence of minimal HE in these 4 who will behave slightly
differently from the remaining 53/57 of the cohort.
6. The authors state that blood sodium levels are important in dictating the
presence or absence of minimal or overt HE in the discussion (ref 34). I’d like to
see some more patient details including whether baseline blood sodium had any
bearing on the presence of minimal HE at baseline or on the response to the
OGC. Likewise what was the serum creatinine (ammonia is also excreted
renally), white cell count and C reactive protein.
- Discretionary Revisions
1. I would change the word ‘attribution’ to ‘distribution’ in the last line of
paragraph 1 of the introduction.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 1Date:12 August 2011
Reviewer: Debbie Shawcross
Reviewer's report:
This study describes an exploration of the role of capillary blood ammonia
estimation in conjunction with a 20 gram oral glutamine challenge (OGC) in 57
patients with advanced cirrhosis with and without a prior history of overt hepatic
encephalopathy (HE). The authors conclude that by itself, capillary blood
ammonia is not a good biomarker of minimal HE and does not reliably predict
future episodes of HE. However, use of the OGC with capillary blood ammonia
estimation improves the diagnostic yield of minimal HE from 44% to 67%.
The notion that isolated blood ammonia level (whether venous or arterial) are
poor predictors of minimal or overt HE has been well established in the literature
by several groups and baseline systemic inflammation has been shown to have
some influence on the cerebral effects of ammonia, in minimal HE using an
amino acid challenge [Shawcross DL, Wright G, Olde Damink SWM and Jalan R.
Role of Ammonia and Inflammation in Minimal Hepatic Encephalopathy.
Metabolic Brain Disease 2007; 22(1):125-38].
The novelty of this study therefore lays in the proposition that OGC and capillary
blood ammonia estimation may be utilised as a point of care diagnostic test for
minimal HE (AUROC 0.727) in patients with cirrhosis. Nevertheless, the time
taken to perform the OGC and 2 sets of neuropsychometry must still have taken
a minimum of 2 hours which may not be feasible to do in all patients presenting
with moderate or advanced cirrhosis.
- Major Compulsory Revisions
1. The authors state that healthy controls were enrolled (Figure 2) and a subset
of patients who had ammonia levels determined simultaneously in 2 vascular
beds (Figure 3). How many controls were used and did they also have
neuropsychomtery performed as well as capillary ammonia? These data need to
be added to the manuscript, table 2 and figure 2. How many patients had 2
vascular beds examined and were they part of the n=57 patients with cirrhosis?
These data need to be added to Figure 3 and discussed in a little more detail in
the manuscript body.
2. The numbers of patients stated to have minimal HE at baseline varies from
45% in the abstract, to 48% in the results and discussion. I calculate 25/57 with
baseline HE to be 44%. Please amend throughout manuscript.
3. The same applies to patients diagnosed with HE post OGC. The abstract says
69% and the results say 67%. I make 38/57 to be 67%. Please amend.
4. This therefore makes me wary that there are other mathematical errors in the
numbers and statistics throughout the manuscript. Please re-check throroughly.
5. It is contentious to give an amino acid challenge to a patient with TIPSS who is
at high risk of developing overt HE as the glutamine will largely bypass the liver.
Previous studies using amino acid challenge and OGC have largely excluded
TIPSS patients. Furthermore, many patients with TIPSS have evidence of
minimal HE at baseline. Please explain the reasoning behind their inclusion and
detail the presence or absence of minimal HE in these 4 who will behave slightly
differently from the remaining 53/57 of the cohort.
6. The authors state that blood sodium levels are important in dictating the
presence or absence of minimal or overt HE in the discussion (ref 34). I’d like to
see some more patient details including whether baseline blood sodium had any
bearing on the presence of minimal HE at baseline or on the response to the
OGC. Likewise what was the serum creatinine (ammonia is also excreted
renally), white cell count and C reactive protein.
- Discretionary Revisions
1. I would change the word ‘attribution’ to ‘distribution’ in the last line of
paragraph 1 of the introduction.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 1Date:12 August 2011
Reviewer: Debbie Shawcross
Reviewer's report:
This study describes an exploration of the role of capillary blood ammonia
estimation in conjunction with a 20 gram oral glutamine challenge (OGC) in 57
patients with advanced cirrhosis with and without a prior history of overt hepatic
encephalopathy (HE). The authors conclude that by itself, capillary blood
ammonia is not a good biomarker of minimal HE and does not reliably predict
future episodes of HE. However, use of the OGC with capillary blood ammonia
estimation improves the diagnostic yield of minimal HE from 44% to 67%.
The notion that isolated blood ammonia level (whether venous or arterial) are
poor predictors of minimal or overt HE has been well established in the literature
by several groups and baseline systemic inflammation has been shown to have
some influence on the cerebral effects of ammonia, in minimal HE using an
amino acid challenge [Shawcross DL, Wright G, Olde Damink SWM and Jalan R.
Role of Ammonia and Inflammation in Minimal Hepatic Encephalopathy.
Metabolic Brain Disease 2007; 22(1):125-38].
The novelty of this study therefore lays in the proposition that OGC and capillary
blood ammonia estimation may be utilised as a point of care diagnostic test for
minimal HE (AUROC 0.727) in patients with cirrhosis. Nevertheless, the time
taken to perform the OGC and 2 sets of neuropsychometry must still have taken
a minimum of 2 hours which may not be feasible to do in all patients presenting
with moderate or advanced cirrhosis.
- Major Compulsory Revisions
1. The authors state that healthy controls were enrolled (Figure 2) and a subset
of patients who had ammonia levels determined simultaneously in 2 vascular
beds (Figure 3). How many controls were used and did they also have
neuropsychomtery performed as well as capillary ammonia? These data need to
be added to the manuscript, table 2 and figure 2. How many patients had 2
vascular beds examined and were they part of the n=57 patients with cirrhosis?
These data need to be added to Figure 3 and discussed in a little more detail in
the manuscript body.
2. The numbers of patients stated to have minimal HE at baseline varies from
45% in the abstract, to 48% in the results and discussion. I calculate 25/57 with
baseline HE to be 44%. Please amend throughout manuscript.
3. The same applies to patients diagnosed with HE post OGC. The abstract says
69% and the results say 67%. I make 38/57 to be 67%. Please amend.
4. This therefore makes me wary that there are other mathematical errors in the
numbers and statistics throughout the manuscript. Please re-check throroughly.
5. It is contentious to give an amino acid challenge to a patient with TIPSS who is
at high risk of developing overt HE as the glutamine will largely bypass the liver.
Previous studies using amino acid challenge and OGC have largely excluded
TIPSS patients. Furthermore, many patients with TIPSS have evidence of
minimal HE at baseline. Please explain the reasoning behind their inclusion and
detail the presence or absence of minimal HE in these 4 who will behave slightly
differently from the remaining 53/57 of the cohort.
6. The authors state that blood sodium levels are important in dictating the
presence or absence of minimal or overt HE in the discussion (ref 34). I’d like to
see some more patient details including whether baseline blood sodium had any
bearing on the presence of minimal HE at baseline or on the response to the
OGC. Likewise what was the serum creatinine (ammonia is also excreted
renally), white cell count and C reactive protein.
- Discretionary Revisions
1. I would change the word ‘attribution’ to ‘distribution’ in the last line of
paragraph 1 of the introduction.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
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