Title: Metabolic Dysfunction, Cirrhosis, and HCV Genotype 3a Drive Type 2 Diabetes Risk in
Chronic Hepatitis C: A Southern Chinese Cohort Study
Version: 2 Date: 07 May 2025
Reviewer's report:
The study addresses a clinically relevant topic, investigating the metabolic risk factors for type
2 diabetes mellitus (T2DM) in patients with chronic hepatitis C virus (CHC) infection. While
the study is generally well-structured and methodologically sound, I have several important
comments and suggestions to improve clarity, analytical rigor, and interpretability:
1. Clarify patient composition in the CHC group
While the CHC/T2DM group included 200 patients (44 outpatients and 156 inpatients), the
manuscript does not report the outpatient/inpatient distribution for the 242 CHC patients. This
information is important, as inpatients typically present with poorer metabolic control and more
advanced disease. The observed differences in ALT, AST, TB, GGT, fasting glucose, insulin,
triglycerides, and HOMA-IR may in part reflect differences in disease severity or underlying
comorbidities rather than T2DM status alone. Please clarify whether this imbalance could have
influenced the observed associations.
2. Potential selection bias due to study setting
As this is a single-center study with a high proportion of hospitalized patients, selection bias
may be present. The baseline characteristics (Table 1) already show statistically significant
differences between groups, which could reflect pre-existing disparities in clinical condition
rather than differences attributable to diabetes status. Please discuss this more explicitly in the
limitations section.
3. Clarify variable inclusion in the multivariate model
The manuscript should explicitly list which variables were included in the multivariate logistic
regression model for adjustment. Please provide this information in the Methods section.
4. Potential confounders related to medication use
It is unclear whether patients in either the CHC or CHC/T2DM group were receiving antiviral
or antidiabetic medications at the time of enrollment. These treatments could significantly affect
laboratory values such as glucose, insulin, or liver enzymes. Please clarify whether medication
use was collected, and if so, whether it was considered in the analyses.
5. Clarification of HOMA-IR findings
In the univariate analysis, HOMA-IR was positively associated with T2DM, which aligns
with current biological understanding. However, the multivariate analysis indicates an inverse
association (OR < 1), which contradicts established literature. This inconsistency requires
clarification.
6. Presentation of comorbidities in tables
In Table 1 and Table 2, comorbidities such as cirrhosis and hypertension are presented as
yes/no categories, but only the "yes" group percentages are shown. It would be clearer to
display only the proportion of patients with each condition, as the "no" percentage is inherently
complementary. Please consider revising the formatting for greater clarity.
7. Figure placement and legend
The legend for Figure 1 should be placed directly below the figure, in accordance with standard
formatting guidelines. This would improve the clarity and professional presentation of the
manuscript.
Title: Metabolic Dysfunction, Cirrhosis, and HCV Genotype 3a Drive Type 2 Diabetes Risk in
Chronic Hepatitis C: A Southern Chinese Cohort Study
Version: 2 Date: 07 May 2025
Reviewer's report:
The study addresses a clinically relevant topic, investigating the metabolic risk factors for type
2 diabetes mellitus (T2DM) in patients with chronic hepatitis C virus (CHC) infection. While
the study is generally well-structured and methodologically sound, I have several important
comments and suggestions to improve clarity, analytical rigor, and interpretability:
1. Clarify patient composition in the CHC group
While the CHC/T2DM group included 200 patients (44 outpatients and 156 inpatients), the
manuscript does not report the outpatient/inpatient distribution for the 242 CHC patients. This
information is important, as inpatients typically present with poorer metabolic control and more
advanced disease. The observed differences in ALT, AST, TB, GGT, fasting glucose, insulin,
triglycerides, and HOMA-IR may in part reflect differences in disease severity or underlying
comorbidities rather than T2DM status alone. Please clarify whether this imbalance could have
influenced the observed associations.
2. Potential selection bias due to study setting
As this is a single-center study with a high proportion of hospitalized patients, selection bias
may be present. The baseline characteristics (Table 1) already show statistically significant
differences between groups, which could reflect pre-existing disparities in clinical condition
rather than differences attributable to diabetes status. Please discuss this more explicitly in the
limitations section.
3. Clarify variable inclusion in the multivariate model
The manuscript should explicitly list which variables were included in the multivariate logistic
regression model for adjustment. Please provide this information in the Methods section.
4. Potential confounders related to medication use
It is unclear whether patients in either the CHC or CHC/T2DM group were receiving antiviral
or antidiabetic medications at the time of enrollment. These treatments could significantly affect
laboratory values such as glucose, insulin, or liver enzymes. Please clarify whether medication
use was collected, and if so, whether it was considered in the analyses.
5. Clarification of HOMA-IR findings
In the univariate analysis, HOMA-IR was positively associated with T2DM, which aligns
with current biological understanding. However, the multivariate analysis indicates an inverse
association (OR < 1), which contradicts established literature. This inconsistency requires
clarification.
6. Presentation of comorbidities in tables
In Table 1 and Table 2, comorbidities such as cirrhosis and hypertension are presented as
yes/no categories, but only the "yes" group percentages are shown. It would be clearer to
display only the proportion of patients with each condition, as the "no" percentage is inherently
complementary. Please consider revising the formatting for greater clarity.
7. Figure placement and legend
The legend for Figure 1 should be placed directly below the figure, in accordance with standard
formatting guidelines. This would improve the clarity and professional presentation of the
manuscript.
Please review this paper.
user
Title: Metabolic Dysfunction, Cirrhosis, and HCV Genotype 3a Drive Type 2 Diabetes Risk in
Chronic Hepatitis C: A Southern Chinese Cohort Study
Version: 2 Date: 07 May 2025
Reviewer's report:
The study addresses a clinically relevant topic, investigating the metabolic risk factors for type
2 diabetes mellitus (T2DM) in patients with chronic hepatitis C virus (CHC) infection. While
the study is generally well-structured and methodologically sound, I have several important
comments and suggestions to improve clarity, analytical rigor, and interpretability:
1. Clarify patient composition in the CHC group
While the CHC/T2DM group included 200 patients (44 outpatients and 156 inpatients), the
manuscript does not report the outpatient/inpatient distribution for the 242 CHC patients. This
information is important, as inpatients typically present with poorer metabolic control and more
advanced disease. The observed differences in ALT, AST, TB, GGT, fasting glucose, insulin,
triglycerides, and HOMA-IR may in part reflect differences in disease severity or underlying
comorbidities rather than T2DM status alone. Please clarify whether this imbalance could have
influenced the observed associations.
2. Potential selection bias due to study setting
As this is a single-center study with a high proportion of hospitalized patients, selection bias
may be present. The baseline characteristics (Table 1) already show statistically significant
differences between groups, which could reflect pre-existing disparities in clinical condition
rather than differences attributable to diabetes status. Please discuss this more explicitly in the
limitations section.
3. Clarify variable inclusion in the multivariate model
The manuscript should explicitly list which variables were included in the multivariate logistic
regression model for adjustment. Please provide this information in the Methods section.
4. Potential confounders related to medication use
It is unclear whether patients in either the CHC or CHC/T2DM group were receiving antiviral
or antidiabetic medications at the time of enrollment. These treatments could significantly affect
laboratory values such as glucose, insulin, or liver enzymes. Please clarify whether medication
use was collected, and if so, whether it was considered in the analyses.
5. Clarification of HOMA-IR findings
In the univariate analysis, HOMA-IR was positively associated with T2DM, which aligns
with current biological understanding. However, the multivariate analysis indicates an inverse
association (OR < 1), which contradicts established literature. This inconsistency requires
clarification.
6. Presentation of comorbidities in tables
In Table 1 and Table 2, comorbidities such as cirrhosis and hypertension are presented as
yes/no categories, but only the "yes" group percentages are shown. It would be clearer to
display only the proportion of patients with each condition, as the "no" percentage is inherently
complementary. Please consider revising the formatting for greater clarity.
7. Figure placement and legend
The legend for Figure 1 should be placed directly below the figure, in accordance with standard
formatting guidelines. This would improve the clarity and professional presentation of the
manuscript.
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