Reviewer's report
Title:A low level of serum total testosterone is independently associated with
nonalcoholic fatty liver disease.
Version: 1Date:24 January 2012
Reviewer: Andreas Geier
Reviewer's report:
Kim and coworkers present a retrospective cohort study investigating the
association of testosterone and non-alcoholic fatty liver disease. This work nicely
complements previous studies in diabetes and metabolic syndrome. The present
study is the first report on testosterone levels in the setting of fatty liver disease.
All data are consistent and adequate presented. Manuscript adheres to the
relevant formal standards for reporting and data deposition. Title and abstract
accurately convey the contents of the study. However, several shortcomings in
the methodology need to be addressed in the manuscript.
Specific comments:
> Most importantly, it has to be mentioned that the gold standard for diagnosis of
a non-alcoholic fatty liver disease still is liver biopsy. This approach also allows to
differentiate NASH from NAFLD, which has not been considered in the present
study. For further analysis of NASH, alternative serological strategies may help to
overcome the missing biopsy in the majority of patients.
> In sonographic examination rounding of dosal liver margin should have also
been used as a parameter in fatty liver disease. If this has been done, the
authors should mention this in the methods section. Also a fibroscan would have
been of interest, especially while lacking histology to judge at least advanced
fibrosis or cirrhosis versus early disease. Comments of direct or indirect signs of
portal hypertension as signs of hepatic cirrhosis resulting in altered testosterone
levels are missing.
> The differential diagnosis of increased echogenicity of liver tissue remains only
incompletely addressed. Incomplete clinical data regarding non-infectious
reasons of hepatic disease or other reasons for sonographic findings as for
example chemotherapy, metabolic or infectious disease are reported. The
completeness of this information cannot be found in the tables.
> While the authors clearly explain the rationale to correlate testosterone levels
with non-alcoholic fatty liver disease, it remains unclear why total testosterone
was analysed and why free testosterone and sex-hormone binding globuline was
not analysed. From the literature, SHBG would be expected to be elevated in
advanced liver disease and cirrhosis thereby resulting in lower levels of free
testosterone. To address this important issue, measurement of SHBG and free
testosterone should be completed if serum samples of patients are still available.
> Testosterone levels peak in the early morning and standard time intervals for
routine diagnostics usually end at 10 A.M. It remains unclear why the authors
decided to exceed this time in favour of increased patient numbers because this
approach definitely limits the comparability of testosterone levels.
> Laboratory data are supposed to be acquired according to good clinical
practice. Why alkaline phophatase and bilirubin are not analysed is not
explained. Furthermore, levels of inflammatory cytokines as TNFa and IL-1 and
sIL-6r would also have been of interest as remarked in discussion. In the context
of inflammation, serum CK 18 as a marker of steatohepatitis in NAFLD would
have been of interest. If serum samples of patients are still available,
measurement of CK 18 should be completed.
> Why was a CT scan performed in all patients (as a routine examination)? Or
was this done for the sole purpose of this study specifically for measurement of
VAT? In this case, an ethics approval may be helpful.
Level of interest: An article whose findings are important to those with closely
related research interests
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
Paper reviewed by Dr. Theodor Kudlich and Prof. Andreas Geier
Reviewer's report
Title:A low level of serum total testosterone is independently associated with
nonalcoholic fatty liver disease.
Version: 1Date:24 January 2012
Reviewer: Andreas Geier
Reviewer's report:
Kim and coworkers present a retrospective cohort study investigating the
association of testosterone and non-alcoholic fatty liver disease. This work nicely
complements previous studies in diabetes and metabolic syndrome. The present
study is the first report on testosterone levels in the setting of fatty liver disease.
All data are consistent and adequate presented. Manuscript adheres to the
relevant formal standards for reporting and data deposition. Title and abstract
accurately convey the contents of the study. However, several shortcomings in
the methodology need to be addressed in the manuscript.
Specific comments:
> Most importantly, it has to be mentioned that the gold standard for diagnosis of
a non-alcoholic fatty liver disease still is liver biopsy. This approach also allows to
differentiate NASH from NAFLD, which has not been considered in the present
study. For further analysis of NASH, alternative serological strategies may help to
overcome the missing biopsy in the majority of patients.
> In sonographic examination rounding of dosal liver margin should have also
been used as a parameter in fatty liver disease. If this has been done, the
authors should mention this in the methods section. Also a fibroscan would have
been of interest, especially while lacking histology to judge at least advanced
fibrosis or cirrhosis versus early disease. Comments of direct or indirect signs of
portal hypertension as signs of hepatic cirrhosis resulting in altered testosterone
levels are missing.
> The differential diagnosis of increased echogenicity of liver tissue remains only
incompletely addressed. Incomplete clinical data regarding non-infectious
reasons of hepatic disease or other reasons for sonographic findings as for
example chemotherapy, metabolic or infectious disease are reported. The
completeness of this information cannot be found in the tables.
> While the authors clearly explain the rationale to correlate testosterone levels
with non-alcoholic fatty liver disease, it remains unclear why total testosterone
was analysed and why free testosterone and sex-hormone binding globuline was
not analysed. From the literature, SHBG would be expected to be elevated in
advanced liver disease and cirrhosis thereby resulting in lower levels of free
testosterone. To address this important issue, measurement of SHBG and free
testosterone should be completed if serum samples of patients are still available.
> Testosterone levels peak in the early morning and standard time intervals for
routine diagnostics usually end at 10 A.M. It remains unclear why the authors
decided to exceed this time in favour of increased patient numbers because this
approach definitely limits the comparability of testosterone levels.
> Laboratory data are supposed to be acquired according to good clinical
practice. Why alkaline phophatase and bilirubin are not analysed is not
explained. Furthermore, levels of inflammatory cytokines as TNFa and IL-1 and
sIL-6r would also have been of interest as remarked in discussion. In the context
of inflammation, serum CK 18 as a marker of steatohepatitis in NAFLD would
have been of interest. If serum samples of patients are still available,
measurement of CK 18 should be completed.
> Why was a CT scan performed in all patients (as a routine examination)? Or
was this done for the sole purpose of this study specifically for measurement of
VAT? In this case, an ethics approval may be helpful.
Level of interest: An article whose findings are important to those with closely
related research interests
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
Paper reviewed by Dr. Theodor Kudlich and Prof. Andreas Geier
Please review this paper.
user
Reviewer's report
Title:A low level of serum total testosterone is independently associated with
nonalcoholic fatty liver disease.
Version: 1Date:24 January 2012
Reviewer: Andreas Geier
Reviewer's report:
Kim and coworkers present a retrospective cohort study investigating the
association of testosterone and non-alcoholic fatty liver disease. This work nicely
complements previous studies in diabetes and metabolic syndrome. The present
study is the first report on testosterone levels in the setting of fatty liver disease.
All data are consistent and adequate presented. Manuscript adheres to the
relevant formal standards for reporting and data deposition. Title and abstract
accurately convey the contents of the study. However, several shortcomings in
the methodology need to be addressed in the manuscript.
Specific comments:
> Most importantly, it has to be mentioned that the gold standard for diagnosis of
a non-alcoholic fatty liver disease still is liver biopsy. This approach also allows to
differentiate NASH from NAFLD, which has not been considered in the present
study. For further analysis of NASH, alternative serological strategies may help to
overcome the missing biopsy in the majority of patients.
> In sonographic examination rounding of dosal liver margin should have also
been used as a parameter in fatty liver disease. If this has been done, the
authors should mention this in the methods section. Also a fibroscan would have
been of interest, especially while lacking histology to judge at least advanced
fibrosis or cirrhosis versus early disease. Comments of direct or indirect signs of
portal hypertension as signs of hepatic cirrhosis resulting in altered testosterone
levels are missing.
> The differential diagnosis of increased echogenicity of liver tissue remains only
incompletely addressed. Incomplete clinical data regarding non-infectious
reasons of hepatic disease or other reasons for sonographic findings as for
example chemotherapy, metabolic or infectious disease are reported. The
completeness of this information cannot be found in the tables.
> While the authors clearly explain the rationale to correlate testosterone levels
with non-alcoholic fatty liver disease, it remains unclear why total testosterone
was analysed and why free testosterone and sex-hormone binding globuline was
not analysed. From the literature, SHBG would be expected to be elevated in
advanced liver disease and cirrhosis thereby resulting in lower levels of free
testosterone. To address this important issue, measurement of SHBG and free
testosterone should be completed if serum samples of patients are still available.
> Testosterone levels peak in the early morning and standard time intervals for
routine diagnostics usually end at 10 A.M. It remains unclear why the authors
decided to exceed this time in favour of increased patient numbers because this
approach definitely limits the comparability of testosterone levels.
> Laboratory data are supposed to be acquired according to good clinical
practice. Why alkaline phophatase and bilirubin are not analysed is not
explained. Furthermore, levels of inflammatory cytokines as TNFa and IL-1 and
sIL-6r would also have been of interest as remarked in discussion. In the context
of inflammation, serum CK 18 as a marker of steatohepatitis in NAFLD would
have been of interest. If serum samples of patients are still available,
measurement of CK 18 should be completed.
> Why was a CT scan performed in all patients (as a routine examination)? Or
was this done for the sole purpose of this study specifically for measurement of
VAT? In this case, an ethics approval may be helpful.
Level of interest: An article whose findings are important to those with closely
related research interests
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
Paper reviewed by Dr. Theodor Kudlich and Prof. Andreas Geier
assistant