Reviewer's report
Title:Plasma Osteopontin is a Biomarker for the Severity of Alcoholic Liver
Cirrhosis, Not for Hepatocellular Carcinoma Screening
Version:3Date:19 April 2015
Reviewer: WING-KIN SYN
Reviewer's report:
Major:
Recruitment of patients: it is unclear if all patients had histologically proven liver
cirrhosis (if not, what proportion had biopsy proven cirrhosis). It is well
recognized that Osteopontin levels are also increased in patients with the
metabolic syndrome (particularly NAFLD / NASH), in the obese, in women, and
in smokers (it would be relevant to cite and discuss the paper by Gual P 2012).
As such, analysis should be corrected for such confounding factors.
It would be important to measure Osteopontin levels from individuals with
non-cirrhotic ALD (i.e. fibrosis) and from healthy blood donors (controls).
Osteopontin levels appear to be upregulated across CP stage (i.e. correlating
with clinical severity) -> please provide relevant statistics in Table 3. Is there any
correlation with MELD?
Like aFP, Osteopontin levels increased with HCC stage - please provide
statistics in Table. Could Osteopontin (with or without aFP) be a useful
non-invasive marker of prognosis? Discuss.
It is unclear how the study was powered - please describe this. The wiide range
of Osteopontin levels detected among HCC (over 2775+ ng/ml) suggest that
investigators should recruit a larger cohort of patients (in this study, there were
only 21 patients with BCLC 0 / A).
Authors should discuss possible limitations of their study - the use of ELISA kit
that detects specific OPN epitopes (in this case, total Osteopontin). Osteopontin
protein undergoes post-translational modification and cleavage by enzymes, and
studies have reported that cleaved Osteopontin may exhibit a better correlation
with disease stage / severity.
Abstract should be re-written to convey key messages - that Osteopontin levels
are a) upregulated with ALD cirrhosis (fibrosis? - see comments above), b)
correlated with clinical severity (CP), and c) HCC BCLC stage, but d) was a poor
biomarker of early HCC.
Minor:
Discussion on points raised above - recruitment, sampling of plasma, confouding
factors, size of cohort.
Please check references - there is duplication - 14 and 23
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
My research expertise includes Osteopontin biology
Reviewer's report
Title:Plasma Osteopontin is a Biomarker for the Severity of Alcoholic Liver
Cirrhosis, Not for Hepatocellular Carcinoma Screening
Version:3Date:19 April 2015
Reviewer: WING-KIN SYN
Reviewer's report:
Major:
Recruitment of patients: it is unclear if all patients had histologically proven liver
cirrhosis (if not, what proportion had biopsy proven cirrhosis). It is well
recognized that Osteopontin levels are also increased in patients with the
metabolic syndrome (particularly NAFLD / NASH), in the obese, in women, and
in smokers (it would be relevant to cite and discuss the paper by Gual P 2012).
As such, analysis should be corrected for such confounding factors.
It would be important to measure Osteopontin levels from individuals with
non-cirrhotic ALD (i.e. fibrosis) and from healthy blood donors (controls).
Osteopontin levels appear to be upregulated across CP stage (i.e. correlating
with clinical severity) -> please provide relevant statistics in Table 3. Is there any
correlation with MELD?
Like aFP, Osteopontin levels increased with HCC stage - please provide
statistics in Table. Could Osteopontin (with or without aFP) be a useful
non-invasive marker of prognosis? Discuss.
It is unclear how the study was powered - please describe this. The wiide range
of Osteopontin levels detected among HCC (over 2775+ ng/ml) suggest that
investigators should recruit a larger cohort of patients (in this study, there were
only 21 patients with BCLC 0 / A).
Authors should discuss possible limitations of their study - the use of ELISA kit
that detects specific OPN epitopes (in this case, total Osteopontin). Osteopontin
protein undergoes post-translational modification and cleavage by enzymes, and
studies have reported that cleaved Osteopontin may exhibit a better correlation
with disease stage / severity.
Abstract should be re-written to convey key messages - that Osteopontin levels
are a) upregulated with ALD cirrhosis (fibrosis? - see comments above), b)
correlated with clinical severity (CP), and c) HCC BCLC stage, but d) was a poor
biomarker of early HCC.
Minor:
Discussion on points raised above - recruitment, sampling of plasma, confouding
factors, size of cohort.
Please check references - there is duplication - 14 and 23
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
My research expertise includes Osteopontin biology
Please review this paper.
user
Reviewer's report
Title:Plasma Osteopontin is a Biomarker for the Severity of Alcoholic Liver
Cirrhosis, Not for Hepatocellular Carcinoma Screening
Version:3Date:19 April 2015
Reviewer: WING-KIN SYN
Reviewer's report:
Major:
Recruitment of patients: it is unclear if all patients had histologically proven liver
cirrhosis (if not, what proportion had biopsy proven cirrhosis). It is well
recognized that Osteopontin levels are also increased in patients with the
metabolic syndrome (particularly NAFLD / NASH), in the obese, in women, and
in smokers (it would be relevant to cite and discuss the paper by Gual P 2012).
As such, analysis should be corrected for such confounding factors.
It would be important to measure Osteopontin levels from individuals with
non-cirrhotic ALD (i.e. fibrosis) and from healthy blood donors (controls).
Osteopontin levels appear to be upregulated across CP stage (i.e. correlating
with clinical severity) -> please provide relevant statistics in Table 3. Is there any
correlation with MELD?
Like aFP, Osteopontin levels increased with HCC stage - please provide
statistics in Table. Could Osteopontin (with or without aFP) be a useful
non-invasive marker of prognosis? Discuss.
It is unclear how the study was powered - please describe this. The wiide range
of Osteopontin levels detected among HCC (over 2775+ ng/ml) suggest that
investigators should recruit a larger cohort of patients (in this study, there were
only 21 patients with BCLC 0 / A).
Authors should discuss possible limitations of their study - the use of ELISA kit
that detects specific OPN epitopes (in this case, total Osteopontin). Osteopontin
protein undergoes post-translational modification and cleavage by enzymes, and
studies have reported that cleaved Osteopontin may exhibit a better correlation
with disease stage / severity.
Abstract should be re-written to convey key messages - that Osteopontin levels
are a) upregulated with ALD cirrhosis (fibrosis? - see comments above), b)
correlated with clinical severity (CP), and c) HCC BCLC stage, but d) was a poor
biomarker of early HCC.
Minor:
Discussion on points raised above - recruitment, sampling of plasma, confouding
factors, size of cohort.
Please check references - there is duplication - 14 and 23
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
My research expertise includes Osteopontin biology
assistant