Title: Associations between non-insulin-based insulin resistance surrogate markers and liver-
related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort
study in South Korea
Version: 3 Date: 24 Feb 2025
Reviewer's report:
The study investigated the link between insulin resistance (IR) surrogate markers and liver-
related outcomes in 66,334 MASLD patients over 9.4 years. Using the TyG index, TG/HDL
ratio, and METS - IR as IR markers, it was found that lower levels of these markers were
associated with a higher risk of liver-related outcomes. The markers increased from F0 - F2 and
decreased from F3 - F4 in liver fibrosis. This indicates the importance of monitoring metabolic
changes in MASLD patients. Nevertheless, certain limitations in this study need to be noted.
1. Insufficient sample size in the liver biopsy cohort
The number of patients with advanced fibrosis (F3 - F4) in the liver biopsy cohort (n = 361) is
relatively small (n = 59), which may reduce the statistical power. It is recommended to expand
the sample size of the liver biopsy cohort or combine data from multiple centers to improve the
reliability of the results.
2. Inadequate explanation of biological mechanisms
The hypotheses proposed in the discussion (such as liver fibrosis leading to a decline in
metabolic parameters) lack direct evidence (e.g., correlation analysis between liver function
indicators and IR markers). It is necessary to supplement the correlation analysis between liver
function indicators (such as albumin, and coagulation function) and IR markers in the liver
biopsy cohort to support the mechanistic hypotheses.
3. Accuracy of disease diagnosis
The use of non-invasive biochemical scores (fatty liver index # 30) to define fatty liver disease
may lead to misdiagnosis compared with liver biopsy or imaging examinations, affecting the
accuracy of the research sample and the reliability of the research conclusions.
4. Assessment of liver-related outcomes
The primary outcomes only include hepatocellular carcinoma and decompensated liver cirrhosis,
without covering other important liver-related outcomes, such as liver failure and the need
for liver transplantation. This may not comprehensively reflect the severity and impact of the
disease.
5. Insufficient subgroup analysisThere is a lack of in-depth analysis of subgroups based on
different genders, ages, and disease severities. This may mask the differences in the relationships
between IR surrogate markers and liver-related outcomes among different subgroups.
6. Impact of drug factors
The study did not consider the effects of drugs that affect metabolism or liver function (such as
statins, and antidiabetic drugs) on IR surrogate markers and liver-related outcomes.
Title: Associations between non-insulin-based insulin resistance surrogate markers and liver-
related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort
study in South Korea
Version: 3 Date: 24 Feb 2025
Reviewer's report:
The study investigated the link between insulin resistance (IR) surrogate markers and liver-
related outcomes in 66,334 MASLD patients over 9.4 years. Using the TyG index, TG/HDL
ratio, and METS - IR as IR markers, it was found that lower levels of these markers were
associated with a higher risk of liver-related outcomes. The markers increased from F0 - F2 and
decreased from F3 - F4 in liver fibrosis. This indicates the importance of monitoring metabolic
changes in MASLD patients. Nevertheless, certain limitations in this study need to be noted.
1. Insufficient sample size in the liver biopsy cohort
The number of patients with advanced fibrosis (F3 - F4) in the liver biopsy cohort (n = 361) is
relatively small (n = 59), which may reduce the statistical power. It is recommended to expand
the sample size of the liver biopsy cohort or combine data from multiple centers to improve the
reliability of the results.
2. Inadequate explanation of biological mechanisms
The hypotheses proposed in the discussion (such as liver fibrosis leading to a decline in
metabolic parameters) lack direct evidence (e.g., correlation analysis between liver function
indicators and IR markers). It is necessary to supplement the correlation analysis between liver
function indicators (such as albumin, and coagulation function) and IR markers in the liver
biopsy cohort to support the mechanistic hypotheses.
3. Accuracy of disease diagnosis
The use of non-invasive biochemical scores (fatty liver index # 30) to define fatty liver disease
may lead to misdiagnosis compared with liver biopsy or imaging examinations, affecting the
accuracy of the research sample and the reliability of the research conclusions.
4. Assessment of liver-related outcomes
The primary outcomes only include hepatocellular carcinoma and decompensated liver cirrhosis,
without covering other important liver-related outcomes, such as liver failure and the need
for liver transplantation. This may not comprehensively reflect the severity and impact of the
disease.
5. Insufficient subgroup analysisThere is a lack of in-depth analysis of subgroups based on
different genders, ages, and disease severities. This may mask the differences in the relationships
between IR surrogate markers and liver-related outcomes among different subgroups.
6. Impact of drug factors
The study did not consider the effects of drugs that affect metabolism or liver function (such as
statins, and antidiabetic drugs) on IR surrogate markers and liver-related outcomes.
Please review this paper.
user
Title: Associations between non-insulin-based insulin resistance surrogate markers and liver-
related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort
study in South Korea
Version: 3 Date: 24 Feb 2025
Reviewer's report:
The study investigated the link between insulin resistance (IR) surrogate markers and liver-
related outcomes in 66,334 MASLD patients over 9.4 years. Using the TyG index, TG/HDL
ratio, and METS - IR as IR markers, it was found that lower levels of these markers were
associated with a higher risk of liver-related outcomes. The markers increased from F0 - F2 and
decreased from F3 - F4 in liver fibrosis. This indicates the importance of monitoring metabolic
changes in MASLD patients. Nevertheless, certain limitations in this study need to be noted.
1. Insufficient sample size in the liver biopsy cohort
The number of patients with advanced fibrosis (F3 - F4) in the liver biopsy cohort (n = 361) is
relatively small (n = 59), which may reduce the statistical power. It is recommended to expand
the sample size of the liver biopsy cohort or combine data from multiple centers to improve the
reliability of the results.
2. Inadequate explanation of biological mechanisms
The hypotheses proposed in the discussion (such as liver fibrosis leading to a decline in
metabolic parameters) lack direct evidence (e.g., correlation analysis between liver function
indicators and IR markers). It is necessary to supplement the correlation analysis between liver
function indicators (such as albumin, and coagulation function) and IR markers in the liver
biopsy cohort to support the mechanistic hypotheses.
3. Accuracy of disease diagnosis
The use of non-invasive biochemical scores (fatty liver index # 30) to define fatty liver disease
may lead to misdiagnosis compared with liver biopsy or imaging examinations, affecting the
accuracy of the research sample and the reliability of the research conclusions.
4. Assessment of liver-related outcomes
The primary outcomes only include hepatocellular carcinoma and decompensated liver cirrhosis,
without covering other important liver-related outcomes, such as liver failure and the need
for liver transplantation. This may not comprehensively reflect the severity and impact of the
disease.
5. Insufficient subgroup analysisThere is a lack of in-depth analysis of subgroups based on
different genders, ages, and disease severities. This may mask the differences in the relationships
between IR surrogate markers and liver-related outcomes among different subgroups.
6. Impact of drug factors
The study did not consider the effects of drugs that affect metabolism or liver function (such as
statins, and antidiabetic drugs) on IR surrogate markers and liver-related outcomes.
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