Title: Branched-chain Amino Acids Supplementation Improves Liver Frailty Index in Frail
Compensated Cirrhotic Patients: A Randomized Controlled Trial
Version: 2 Date: 03 Mar 2023
Reviewer's report:
This is a 16-week, single center randomized trial of BCAA supplementation (twice daily) - 26
g of protein among patients with frailty and cirrhosis. LFI decreased by 0.36 points vs. 0.14
in intervention vs. control. There was a 4-week run  in period with counseling and exercise
recommendations for both groups.
The patients were largely child A and some were child C. The proportion of frailty reversion
was about 1/3 in intervention and none in the control group.
Quality of life (physical and mental) improved in the BCAA group and not in the  control group.
Frailty reversion is important and protein supplementation has potential to combat frailty and
reverse sarcopenia. The methods are clear and the manuscript is well-written.
My main questions are :
1. It is difficult to believe that there would be some many patients who are currently frail and
without recent decompensations. When was frailty measured? How many patients ruled out
the study  for not meeting frailty criteria? This should be included in the CONSORT diagram.
It seems that most of the patient met frailty criteria due to concomitant cirrhosis and older
age, but non on the  basis of decompensation. I am willing to accept this, but please provide
more information on how many were not candidates due to decompensations and due to lack
of meeting frailty criteria.
2. How was body composition measured? BIA is only mentioned in the discussion. This should
also be in the methods.
3. Beyond 2-week monitoring and BCAA, did the intervention group receive any other
counseling?
4. Figure 2 is a bit confusing to interpret. The Figure legends should clearly specify what is
shown in  each panel.
5. Discussion should specify that the findings do not apply to patients with decompensated
cirrhosis (if i am reading the exclusion criteria correctly). Future studies should evaluate
BCAA for decompensated cirrhosis and also compared BCAA to standard dietary protein
supplementation (nighttime snack).
Title: Branched-chain Amino Acids Supplementation Improves Liver Frailty Index in Frail
Compensated Cirrhotic Patients: A Randomized Controlled Trial
Version: 2 Date: 03 Mar 2023
Reviewer's report:
This is a 16-week, single center randomized trial of BCAA supplementation (twice daily) - 26
g of protein among patients with frailty and cirrhosis. LFI decreased by 0.36 points vs. 0.14
in intervention vs. control. There was a 4-week run  in period with counseling and exercise
recommendations for both groups.
The patients were largely child A and some were child C. The proportion of frailty reversion
was about 1/3 in intervention and none in the control group.
Quality of life (physical and mental) improved in the BCAA group and not in the  control group.
Frailty reversion is important and protein supplementation has potential to combat frailty and
reverse sarcopenia. The methods are clear and the manuscript is well-written.
My main questions are :
1. It is difficult to believe that there would be some many patients who are currently frail and
without recent decompensations. When was frailty measured? How many patients ruled out
the study  for not meeting frailty criteria? This should be included in the CONSORT diagram.
It seems that most of the patient met frailty criteria due to concomitant cirrhosis and older
age, but non on the  basis of decompensation. I am willing to accept this, but please provide
more information on how many were not candidates due to decompensations and due to lack
of meeting frailty criteria.
2. How was body composition measured? BIA is only mentioned in the discussion. This should
also be in the methods.
3. Beyond 2-week monitoring and BCAA, did the intervention group receive any other
counseling?
4. Figure 2 is a bit confusing to interpret. The Figure legends should clearly specify what is
shown in  each panel.
5. Discussion should specify that the findings do not apply to patients with decompensated
cirrhosis (if i am reading the exclusion criteria correctly). Future studies should evaluate
BCAA for decompensated cirrhosis and also compared BCAA to standard dietary protein
supplementation (nighttime snack).
Please review this paper.
user
Title: Branched-chain Amino Acids Supplementation Improves Liver Frailty Index in Frail
Compensated Cirrhotic Patients: A Randomized Controlled Trial
Version: 2 Date: 03 Mar 2023
Reviewer's report:
This is a 16-week, single center randomized trial of BCAA supplementation (twice daily) - 26
g of protein among patients with frailty and cirrhosis. LFI decreased by 0.36 points vs. 0.14
in intervention vs. control. There was a 4-week run  in period with counseling and exercise
recommendations for both groups.
The patients were largely child A and some were child C. The proportion of frailty reversion
was about 1/3 in intervention and none in the control group.
Quality of life (physical and mental) improved in the BCAA group and not in the  control group.
Frailty reversion is important and protein supplementation has potential to combat frailty and
reverse sarcopenia. The methods are clear and the manuscript is well-written.
My main questions are :
1. It is difficult to believe that there would be some many patients who are currently frail and
without recent decompensations. When was frailty measured? How many patients ruled out
the study  for not meeting frailty criteria? This should be included in the CONSORT diagram.
It seems that most of the patient met frailty criteria due to concomitant cirrhosis and older
age, but non on the  basis of decompensation. I am willing to accept this, but please provide
more information on how many were not candidates due to decompensations and due to lack
of meeting frailty criteria.
2. How was body composition measured? BIA is only mentioned in the discussion. This should
also be in the methods.
3. Beyond 2-week monitoring and BCAA, did the intervention group receive any other
counseling?
4. Figure 2 is a bit confusing to interpret. The Figure legends should clearly specify what is
shown in  each panel.
5. Discussion should specify that the findings do not apply to patients with decompensated
cirrhosis (if i am reading the exclusion criteria correctly). Future studies should evaluate
BCAA for decompensated cirrhosis and also compared BCAA to standard dietary protein
supplementation (nighttime snack).
assistant