Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:11 June 2015
Reviewer: Rita Garcia Martinez
Reviewer's report:
Salerno et al perform a meta-analysis aiming to investigate the impact of the
albumin dose in the treatment of patients with type 1 hepatorrenal syndrome. The
paper is appropriate, opportune and the question is important, however several
shortcomings deserve further discussion.
Major comments:
1. Methods
• Inclusion of non-randomized studies.. The authors recognize the potential risk
bias of including non-randomized trials, however, the fact that more than half of
the included trials are non-randomized increases this risk and may decreases the
quality of results.
• To my understanding survival and cumulative dose of albumin may be
competitive events since cumulative dose of albumin depends on daily dose plus
days of survival receiving albumin. I wonder whether the events associated to
survival, including dose of albumin would be better analysed using competitive
risk methodology.
2. Results:
• Albumin dose:
- The authors found an association between the cumulative dose of albumin and
survival. However there is only a trend between survival and HRS reversal. If
albumin dose leads to an improvement in survival (causative association) it
would be expected an association also with HRS reversal. The lack of this
association do not support a causative association between albumin cumulative
dose and improvement in survival. The authors defend in the discussion a
causative association. They state that a higher cumulative dose would be due to
longer survival if higher cumulative dose was associated to longer survival. This
is only partially true, since cumulative dose would be more related to HRS
duration and not directly to survival. The establishment of a causative association
is not that clear in the basis of the authors findings and they should moderate
their statements.
• It is surprising that the authors do not find any association with other variables
already known to be important in HRS reversal, such as bilirubin,
vasoconstrictors, basal creatinine... Also another important predicting factor of
HRS is baseline coagulation parameters... Since these are not available, the
statements on the impact of albumin in HRS and survival need to be temperated.
3. Relevance:
• Although there could be a potential benefit on the treatment of HRS type 1 of
higher dose of albumin, the term "cumulative albumin dose" might not be really
useful in clinical practice. It is difficult to predict the length of treatment at
baseline, that is why a daily basis schedule of treatment is preferred. This
practical issue aimed to be resolved is not finally answered in this paper. This is
an open question for prospective studies.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:11 June 2015
Reviewer: Rita Garcia Martinez
Reviewer's report:
Salerno et al perform a meta-analysis aiming to investigate the impact of the
albumin dose in the treatment of patients with type 1 hepatorrenal syndrome. The
paper is appropriate, opportune and the question is important, however several
shortcomings deserve further discussion.
Major comments:
1. Methods
• Inclusion of non-randomized studies.. The authors recognize the potential risk
bias of including non-randomized trials, however, the fact that more than half of
the included trials are non-randomized increases this risk and may decreases the
quality of results.
• To my understanding survival and cumulative dose of albumin may be
competitive events since cumulative dose of albumin depends on daily dose plus
days of survival receiving albumin. I wonder whether the events associated to
survival, including dose of albumin would be better analysed using competitive
risk methodology.
2. Results:
• Albumin dose:
- The authors found an association between the cumulative dose of albumin and
survival. However there is only a trend between survival and HRS reversal. If
albumin dose leads to an improvement in survival (causative association) it
would be expected an association also with HRS reversal. The lack of this
association do not support a causative association between albumin cumulative
dose and improvement in survival. The authors defend in the discussion a
causative association. They state that a higher cumulative dose would be due to
longer survival if higher cumulative dose was associated to longer survival. This
is only partially true, since cumulative dose would be more related to HRS
duration and not directly to survival. The establishment of a causative association
is not that clear in the basis of the authors findings and they should moderate
their statements.
• It is surprising that the authors do not find any association with other variables
already known to be important in HRS reversal, such as bilirubin,
vasoconstrictors, basal creatinine... Also another important predicting factor of
HRS is baseline coagulation parameters... Since these are not available, the
statements on the impact of albumin in HRS and survival need to be temperated.
3. Relevance:
• Although there could be a potential benefit on the treatment of HRS type 1 of
higher dose of albumin, the term "cumulative albumin dose" might not be really
useful in clinical practice. It is difficult to predict the length of treatment at
baseline, that is why a daily basis schedule of treatment is preferred. This
practical issue aimed to be resolved is not finally answered in this paper. This is
an open question for prospective studies.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:11 June 2015
Reviewer: Rita Garcia Martinez
Reviewer's report:
Salerno et al perform a meta-analysis aiming to investigate the impact of the
albumin dose in the treatment of patients with type 1 hepatorrenal syndrome. The
paper is appropriate, opportune and the question is important, however several
shortcomings deserve further discussion.
Major comments:
1. Methods
• Inclusion of non-randomized studies.. The authors recognize the potential risk
bias of including non-randomized trials, however, the fact that more than half of
the included trials are non-randomized increases this risk and may decreases the
quality of results.
• To my understanding survival and cumulative dose of albumin may be
competitive events since cumulative dose of albumin depends on daily dose plus
days of survival receiving albumin. I wonder whether the events associated to
survival, including dose of albumin would be better analysed using competitive
risk methodology.
2. Results:
• Albumin dose:
- The authors found an association between the cumulative dose of albumin and
survival. However there is only a trend between survival and HRS reversal. If
albumin dose leads to an improvement in survival (causative association) it
would be expected an association also with HRS reversal. The lack of this
association do not support a causative association between albumin cumulative
dose and improvement in survival. The authors defend in the discussion a
causative association. They state that a higher cumulative dose would be due to
longer survival if higher cumulative dose was associated to longer survival. This
is only partially true, since cumulative dose would be more related to HRS
duration and not directly to survival. The establishment of a causative association
is not that clear in the basis of the authors findings and they should moderate
their statements.
• It is surprising that the authors do not find any association with other variables
already known to be important in HRS reversal, such as bilirubin,
vasoconstrictors, basal creatinine... Also another important predicting factor of
HRS is baseline coagulation parameters... Since these are not available, the
statements on the impact of albumin in HRS and survival need to be temperated.
3. Relevance:
• Although there could be a potential benefit on the treatment of HRS type 1 of
higher dose of albumin, the term "cumulative albumin dose" might not be really
useful in clinical practice. It is difficult to predict the length of treatment at
baseline, that is why a daily basis schedule of treatment is preferred. This
practical issue aimed to be resolved is not finally answered in this paper. This is
an open question for prospective studies.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
assistant