Title: High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver
transplantation and the role of controlled attenuation parameter
Version: 1 Date: 20 Apr 2023
Reviewer's report:
Dear authors
Comments to authors:
In this study, Mak et al address that High prevalence of de novo metabolic dysfunction-
associated fatty liver disease after liver transplantation. This study aimed to determine the
prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease
(MAFLD) after LT. Controlled attenuation parameter (CAP) was compared with implant liver
biopsy, and also validated in 42 patients with post-LT liver biopsy. The optimal cut-off level
of CAP for diagnosing at least mild (#S1) and moderate-to-severe steatosis (#S2/3) was 266
and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly
derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria
for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR
2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR
4.85) were associated with the development of S2/3 graft steatosis. There was no significant
difference in the median liver stiffness between those with S2/3 and S0/1 steatosis (5.4 kPa vs
4.9 kPa, p=0.091). In conclusion, although NAFLD remains an uncommon primary liver disease
indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and
the majority is classified as MAFLD. Development of graft steatosis is not associated with an
increase in graft dysfunction or fibrosis.
COMMENTS
The study is interest and there is some space for improvement. In particular, as presented the
study looks too descriptive in nature with some insights for the observations made.
1. The optimal cut-off level of CAP for diagnosing at least mild (#S1) was 266 dB/m, with
AUROC of 0.740. The AUROC of 0.740 is not good. Do you have a higher AUROC for at
least mild (#S1)?
2. A total of 879 patients underwent LT is a large series for LT and 571 had transient elastography
performed. Why were only 42 patients undergoing biopsy?
3. After LT, 192, 389, and 164 patients developed new onset DM, hypertension, and
dyslipidemia with cumulative rate of 17.9%, 23.8%, and 2.5%, respectively at 1 years. 28.9%
patients have de novo NAFLD. Why was the high perveance for de novo NAFLD, DM,
hypertension, and dyslipidemia?
4. 42 patients with post-LT liver biopsy were done and Correlation of CAP with liver biopsy
after liver transplantation. Do you have CAP data or pathology reports of donor liver before LT
in 42 patients with post-LT liver biopsy?
5. Development of graft steatosis is not associated with an increase in graft dysfunction or
fibrosis. Why is graft steatosis not associated with an increase in graft dysfunction or fibrosis?
Title: High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver
transplantation and the role of controlled attenuation parameter
Version: 1 Date: 20 Apr 2023
Reviewer's report:
Dear authors
Comments to authors:
In this study, Mak et al address that High prevalence of de novo metabolic dysfunction-
associated fatty liver disease after liver transplantation. This study aimed to determine the
prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease
(MAFLD) after LT. Controlled attenuation parameter (CAP) was compared with implant liver
biopsy, and also validated in 42 patients with post-LT liver biopsy. The optimal cut-off level
of CAP for diagnosing at least mild (#S1) and moderate-to-severe steatosis (#S2/3) was 266
and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly
derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria
for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR
2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR
4.85) were associated with the development of S2/3 graft steatosis. There was no significant
difference in the median liver stiffness between those with S2/3 and S0/1 steatosis (5.4 kPa vs
4.9 kPa, p=0.091). In conclusion, although NAFLD remains an uncommon primary liver disease
indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and
the majority is classified as MAFLD. Development of graft steatosis is not associated with an
increase in graft dysfunction or fibrosis.
COMMENTS
The study is interest and there is some space for improvement. In particular, as presented the
study looks too descriptive in nature with some insights for the observations made.
1. The optimal cut-off level of CAP for diagnosing at least mild (#S1) was 266 dB/m, with
AUROC of 0.740. The AUROC of 0.740 is not good. Do you have a higher AUROC for at
least mild (#S1)?
2. A total of 879 patients underwent LT is a large series for LT and 571 had transient elastography
performed. Why were only 42 patients undergoing biopsy?
3. After LT, 192, 389, and 164 patients developed new onset DM, hypertension, and
dyslipidemia with cumulative rate of 17.9%, 23.8%, and 2.5%, respectively at 1 years. 28.9%
patients have de novo NAFLD. Why was the high perveance for de novo NAFLD, DM,
hypertension, and dyslipidemia?
4. 42 patients with post-LT liver biopsy were done and Correlation of CAP with liver biopsy
after liver transplantation. Do you have CAP data or pathology reports of donor liver before LT
in 42 patients with post-LT liver biopsy?
5. Development of graft steatosis is not associated with an increase in graft dysfunction or
fibrosis. Why is graft steatosis not associated with an increase in graft dysfunction or fibrosis?
Please review this paper.
user
Title: High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver
transplantation and the role of controlled attenuation parameter
Version: 1 Date: 20 Apr 2023
Reviewer's report:
Dear authors
Comments to authors:
In this study, Mak et al address that High prevalence of de novo metabolic dysfunction-
associated fatty liver disease after liver transplantation. This study aimed to determine the
prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease
(MAFLD) after LT. Controlled attenuation parameter (CAP) was compared with implant liver
biopsy, and also validated in 42 patients with post-LT liver biopsy. The optimal cut-off level
of CAP for diagnosing at least mild (#S1) and moderate-to-severe steatosis (#S2/3) was 266
and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly
derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria
for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR
2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR
4.85) were associated with the development of S2/3 graft steatosis. There was no significant
difference in the median liver stiffness between those with S2/3 and S0/1 steatosis (5.4 kPa vs
4.9 kPa, p=0.091). In conclusion, although NAFLD remains an uncommon primary liver disease
indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and
the majority is classified as MAFLD. Development of graft steatosis is not associated with an
increase in graft dysfunction or fibrosis.
COMMENTS
The study is interest and there is some space for improvement. In particular, as presented the
study looks too descriptive in nature with some insights for the observations made.
1. The optimal cut-off level of CAP for diagnosing at least mild (#S1) was 266 dB/m, with
AUROC of 0.740. The AUROC of 0.740 is not good. Do you have a higher AUROC for at
least mild (#S1)?
2. A total of 879 patients underwent LT is a large series for LT and 571 had transient elastography
performed. Why were only 42 patients undergoing biopsy?
3. After LT, 192, 389, and 164 patients developed new onset DM, hypertension, and
dyslipidemia with cumulative rate of 17.9%, 23.8%, and 2.5%, respectively at 1 years. 28.9%
patients have de novo NAFLD. Why was the high perveance for de novo NAFLD, DM,
hypertension, and dyslipidemia?
4. 42 patients with post-LT liver biopsy were done and Correlation of CAP with liver biopsy
after liver transplantation. Do you have CAP data or pathology reports of donor liver before LT
in 42 patients with post-LT liver biopsy?
5. Development of graft steatosis is not associated with an increase in graft dysfunction or
fibrosis. Why is graft steatosis not associated with an increase in graft dysfunction or fibrosis?
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