Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 1 Date: 04 Jan 2021
Reviewer's report:
This is an interesting study that evaluated the prognostic potential of serum ferritin in the
long-term follow-up of cirrhotic outpatients. Total 244 patients with  liver cirrhosis were
enrolled for study analysis. The authors noted that lower (<40µg/L) ferritin concentration was
associated with the development of decompensated clinical stage in patients with previously
compensated cirrhosis. Female sex of the patients, presence of ascites, previous bacterial
infection episode and high serum ferritin concentration were independent risk factors of bacteria
infection development. High ferritin levels were associated with increased mortality rate in all
these groups
Major Comments:
1. Introduction: The major issue is the clinical reasoning to use the ferritin level to predict the
prognosis of long-term mortality in cirrhotic patients. Serum ferritin is almost entirely made up
of L chains and has a half#life of 30 h. Serum ferritin shows an acute phase response such that
levels may be raised beyond that appropriate for reticuloendothelial system (RES) iron stores
by inflammation or by tissue damage. Levels in serum will also be raised by any condition or
treatment (e.g. blood transfusion or iron infusion) that lead to a genuine increase in RES iron
stores. Using a single test of a biomarker with short half-life to predict the prognosis of long
term mortality seems not reasonable.
2. Patient population (Page 5): Strictly speaking, cirrhosis is a pathological diagnosis; it is,
nevertheless, usually diagnosed clinically, by history, physical examination (e.g., cutaneous
signs of liver disease), image (e.g., ultrasonography, transient elastography) and laboratory
analyses (e,g., APRI, FIB-4). The diagnosis criteria for liver cirrhosis should be clarify in this
study. The number of patients diangosis by clinical, biochemical, imaging or liver biopsy need
to be reported
3. Patient population (Page 5): How many people diagnosed with cirrhosis during the study
period?  How many people excluded in this study? Please report numbers of individuals at each
stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible,
included in the study, completing follow-up, and analyses. Give numbers for non-participation
at each stage. Consider the use of a flow diagram.
4. Patient population (Page 5): The authors excluded the patient with positive hemochromatosis
test. What kind of tests were done(mutation in HFE gene, liver biopsy or MRI)?
5. Results: Could we used th eferritin concentration to predict the development of acute
decompensated in patients with previously decompensated cirrhosis?
Minor comment:
1. Patient population (Page 6): How about the diagnosis criteria of bacteria infection?
2. Patient population (Table 1): Please report the serum ferritin level of each group.
3. Results:  Please report the numbers with low and high serum ferritine level in compensated
and decompensated groups.
4. Results (P13): The authors reports 20 patients with AD. The bacteria infection is usually
associated with HE or varices bleeding. Please report the number of bacteria infection.
Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 1 Date: 04 Jan 2021
Reviewer's report:
This is an interesting study that evaluated the prognostic potential of serum ferritin in the
long-term follow-up of cirrhotic outpatients. Total 244 patients with  liver cirrhosis were
enrolled for study analysis. The authors noted that lower (<40µg/L) ferritin concentration was
associated with the development of decompensated clinical stage in patients with previously
compensated cirrhosis. Female sex of the patients, presence of ascites, previous bacterial
infection episode and high serum ferritin concentration were independent risk factors of bacteria
infection development. High ferritin levels were associated with increased mortality rate in all
these groups
Major Comments:
1. Introduction: The major issue is the clinical reasoning to use the ferritin level to predict the
prognosis of long-term mortality in cirrhotic patients. Serum ferritin is almost entirely made up
of L chains and has a half#life of 30 h. Serum ferritin shows an acute phase response such that
levels may be raised beyond that appropriate for reticuloendothelial system (RES) iron stores
by inflammation or by tissue damage. Levels in serum will also be raised by any condition or
treatment (e.g. blood transfusion or iron infusion) that lead to a genuine increase in RES iron
stores. Using a single test of a biomarker with short half-life to predict the prognosis of long
term mortality seems not reasonable.
2. Patient population (Page 5): Strictly speaking, cirrhosis is a pathological diagnosis; it is,
nevertheless, usually diagnosed clinically, by history, physical examination (e.g., cutaneous
signs of liver disease), image (e.g., ultrasonography, transient elastography) and laboratory
analyses (e,g., APRI, FIB-4). The diagnosis criteria for liver cirrhosis should be clarify in this
study. The number of patients diangosis by clinical, biochemical, imaging or liver biopsy need
to be reported
3. Patient population (Page 5): How many people diagnosed with cirrhosis during the study
period?  How many people excluded in this study? Please report numbers of individuals at each
stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible,
included in the study, completing follow-up, and analyses. Give numbers for non-participation
at each stage. Consider the use of a flow diagram.
4. Patient population (Page 5): The authors excluded the patient with positive hemochromatosis
test. What kind of tests were done(mutation in HFE gene, liver biopsy or MRI)?
5. Results: Could we used th eferritin concentration to predict the development of acute
decompensated in patients with previously decompensated cirrhosis?
Minor comment:
1. Patient population (Page 6): How about the diagnosis criteria of bacteria infection?
2. Patient population (Table 1): Please report the serum ferritin level of each group.
3. Results:  Please report the numbers with low and high serum ferritine level in compensated
and decompensated groups.
4. Results (P13): The authors reports 20 patients with AD. The bacteria infection is usually
associated with HE or varices bleeding. Please report the number of bacteria infection.
Please review this paper.
user
Title: Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients:
a cohort study
Version: 1 Date: 04 Jan 2021
Reviewer's report:
This is an interesting study that evaluated the prognostic potential of serum ferritin in the
long-term follow-up of cirrhotic outpatients. Total 244 patients with  liver cirrhosis were
enrolled for study analysis. The authors noted that lower (<40µg/L) ferritin concentration was
associated with the development of decompensated clinical stage in patients with previously
compensated cirrhosis. Female sex of the patients, presence of ascites, previous bacterial
infection episode and high serum ferritin concentration were independent risk factors of bacteria
infection development. High ferritin levels were associated with increased mortality rate in all
these groups
Major Comments:
1. Introduction: The major issue is the clinical reasoning to use the ferritin level to predict the
prognosis of long-term mortality in cirrhotic patients. Serum ferritin is almost entirely made up
of L chains and has a half#life of 30 h. Serum ferritin shows an acute phase response such that
levels may be raised beyond that appropriate for reticuloendothelial system (RES) iron stores
by inflammation or by tissue damage. Levels in serum will also be raised by any condition or
treatment (e.g. blood transfusion or iron infusion) that lead to a genuine increase in RES iron
stores. Using a single test of a biomarker with short half-life to predict the prognosis of long
term mortality seems not reasonable.
2. Patient population (Page 5): Strictly speaking, cirrhosis is a pathological diagnosis; it is,
nevertheless, usually diagnosed clinically, by history, physical examination (e.g., cutaneous
signs of liver disease), image (e.g., ultrasonography, transient elastography) and laboratory
analyses (e,g., APRI, FIB-4). The diagnosis criteria for liver cirrhosis should be clarify in this
study. The number of patients diangosis by clinical, biochemical, imaging or liver biopsy need
to be reported
3. Patient population (Page 5): How many people diagnosed with cirrhosis during the study
period?  How many people excluded in this study? Please report numbers of individuals at each
stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible,
included in the study, completing follow-up, and analyses. Give numbers for non-participation
at each stage. Consider the use of a flow diagram.
4. Patient population (Page 5): The authors excluded the patient with positive hemochromatosis
test. What kind of tests were done(mutation in HFE gene, liver biopsy or MRI)?
5. Results: Could we used th eferritin concentration to predict the development of acute
decompensated in patients with previously decompensated cirrhosis?
Minor comment:
1. Patient population (Page 6): How about the diagnosis criteria of bacteria infection?
2. Patient population (Table 1): Please report the serum ferritin level of each group.
3. Results:  Please report the numbers with low and high serum ferritine level in compensated
and decompensated groups.
4. Results (P13): The authors reports 20 patients with AD. The bacteria infection is usually
associated with HE or varices bleeding. Please report the number of bacteria infection.
assistant