Reviewer's report
Title:Impaired Mitochondrial beta-Oxidation in Patients with Chronic Hepatitis C:
Relation with Viral Load and Insulin Resistance
Version: 1Date:8 April 2013
Reviewer: Hironori Mitsuyoshi
Reviewer's report:
In this manuscript, Sato et al. examined hepatic fatty acid oxidation in patients
with HCV infection. They showed that hepatic oxidation was significantly
decreased in HCV patients compared to healthy controls and that the decreased
rate was associated with serum core antigen levels and the index of insulin
resistance. The mechanisms by which HCV infection promotes hepatic steatosis
would involve multiple steps. The findings are interesting. However, I have
several questions regarding their results and discussion.
- Major Compulsory Revisions
1. The authors showed that hepatic fatty acid oxidation was decreased in HCV
patients. However, the decrease in oxidation was not significantly associated with
the grade of steatosis. What is the clinical implication of the impairment of fatty
acid oxidation?
2. The authors speculated that the decrease in fatty acid oxidation was
associated with insulin resistance (Discussion, 7th paragraph). This suggestion
is seemingly curious, since insulin resistance generally results in the increase in
serum fatty acid levels. The increased serum fatty acids may accelerate hepatic
fatty acid oxidation as the authors showed in Figure 4B. The relationships
between them should be discussed in more detail.
3. The authors discussed that “ triglyceride accumulation in the hepatocytes due
to the impairment of mitochondrial beta-oxidation leads to insulin resistance
(Discussion, 7th paragraph).” However, it has been described that lipid
accumulation in the liver does not necessarily cause the insulin resistance
(Schonfeld et al. Trans Am Clin Climatol Assoc 2008; 119: 217–24). It should be
discussed.
4. The authors described that the increase in the core protein levels leads to the
decrease in the rate of hepatic oxidation (Discussion, 5th paragraph). Because
HCV replication prefers lipid rich circumstances, it can be assumed that the
increase in the core protein levels are the results, not cause, of decreased fatty
acid oxidation. They should be discussed.
5. The authors evaluated hepatic fatty acid oxidation by the rate of change in
ketone body concentration between 12h and 15h after the start of fasting
(Methods, fasting test). Why did they measure ketone body levels at 2 times? Is
this method more accurate than one point measurement? If so, it should be
described.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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:Impaired Mitochondrial beta-Oxidation in Patients with Chronic Hepatitis C:
Relation with Viral Load and Insulin Resistance
Version: 1Date:8 April 2013
Reviewer: Hironori Mitsuyoshi
Reviewer's report:
In this manuscript, Sato et al. examined hepatic fatty acid oxidation in patients
with HCV infection. They showed that hepatic oxidation was significantly
decreased in HCV patients compared to healthy controls and that the decreased
rate was associated with serum core antigen levels and the index of insulin
resistance. The mechanisms by which HCV infection promotes hepatic steatosis
would involve multiple steps. The findings are interesting. However, I have
several questions regarding their results and discussion.
- Major Compulsory Revisions
1. The authors showed that hepatic fatty acid oxidation was decreased in HCV
patients. However, the decrease in oxidation was not significantly associated with
the grade of steatosis. What is the clinical implication of the impairment of fatty
acid oxidation?
2. The authors speculated that the decrease in fatty acid oxidation was
associated with insulin resistance (Discussion, 7th paragraph). This suggestion
is seemingly curious, since insulin resistance generally results in the increase in
serum fatty acid levels. The increased serum fatty acids may accelerate hepatic
fatty acid oxidation as the authors showed in Figure 4B. The relationships
between them should be discussed in more detail.
3. The authors discussed that “ triglyceride accumulation in the hepatocytes due
to the impairment of mitochondrial beta-oxidation leads to insulin resistance
(Discussion, 7th paragraph).” However, it has been described that lipid
accumulation in the liver does not necessarily cause the insulin resistance
(Schonfeld et al. Trans Am Clin Climatol Assoc 2008; 119: 217–24). It should be
discussed.
4. The authors described that the increase in the core protein levels leads to the
decrease in the rate of hepatic oxidation (Discussion, 5th paragraph). Because
HCV replication prefers lipid rich circumstances, it can be assumed that the
increase in the core protein levels are the results, not cause, of decreased fatty
acid oxidation. They should be discussed.
5. The authors evaluated hepatic fatty acid oxidation by the rate of change in
ketone body concentration between 12h and 15h after the start of fasting
(Methods, fasting test). Why did they measure ketone body levels at 2 times? Is
this method more accurate than one point measurement? If so, it should be
described.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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:Impaired Mitochondrial beta-Oxidation in Patients with Chronic Hepatitis C:
Relation with Viral Load and Insulin Resistance
Version: 1Date:8 April 2013
Reviewer: Hironori Mitsuyoshi
Reviewer's report:
In this manuscript, Sato et al. examined hepatic fatty acid oxidation in patients
with HCV infection. They showed that hepatic oxidation was significantly
decreased in HCV patients compared to healthy controls and that the decreased
rate was associated with serum core antigen levels and the index of insulin
resistance. The mechanisms by which HCV infection promotes hepatic steatosis
would involve multiple steps. The findings are interesting. However, I have
several questions regarding their results and discussion.
- Major Compulsory Revisions
1. The authors showed that hepatic fatty acid oxidation was decreased in HCV
patients. However, the decrease in oxidation was not significantly associated with
the grade of steatosis. What is the clinical implication of the impairment of fatty
acid oxidation?
2. The authors speculated that the decrease in fatty acid oxidation was
associated with insulin resistance (Discussion, 7th paragraph). This suggestion
is seemingly curious, since insulin resistance generally results in the increase in
serum fatty acid levels. The increased serum fatty acids may accelerate hepatic
fatty acid oxidation as the authors showed in Figure 4B. The relationships
between them should be discussed in more detail.
3. The authors discussed that “ triglyceride accumulation in the hepatocytes due
to the impairment of mitochondrial beta-oxidation leads to insulin resistance
(Discussion, 7th paragraph).” However, it has been described that lipid
accumulation in the liver does not necessarily cause the insulin resistance
(Schonfeld et al. Trans Am Clin Climatol Assoc 2008; 119: 217–24). It should be
discussed.
4. The authors described that the increase in the core protein levels leads to the
decrease in the rate of hepatic oxidation (Discussion, 5th paragraph). Because
HCV replication prefers lipid rich circumstances, it can be assumed that the
increase in the core protein levels are the results, not cause, of decreased fatty
acid oxidation. They should be discussed.
5. The authors evaluated hepatic fatty acid oxidation by the rate of change in
ketone body concentration between 12h and 15h after the start of fasting
(Methods, fasting test). Why did they measure ketone body levels at 2 times? Is
this method more accurate than one point measurement? If so, it should be
described.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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.
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