Review for 10.1186/1471-230X-12-84 (2012)

Reviewer's report
Title:Predicting incident fatty liver at 4.37 year follow up, using simple
cardio-metabolic risk factors at baseline
Version: 1Date:27 April 2012
Reviewer: Andrew Yeoman
Reviewer's report:
The manuscript "Predicting incident fatty liver at 4.37 year follow up, using simple
cardio-metabolic risk factors at baseline" by Sung et al is an attempt to address a
major problem: namely that of who is most likely to have non-alcoholic fatty liver
disease (NAFLD).
The article is well written and represents the synthesis of an enormous amount of
work and the authors are to be congratulated on their efforts. Furthermore they
appear to identify 5 risk factors which, when combined, and when using the
refined thresholds they identify in the study, improve the sensitivity for the
presence of moderate steatosis on USS.
However there are a number of limitations to the manuscript that hinder its
impact and therefore I feel require further consideration.
Major Compulsory Revisions:
1) By using abdominal USS as the arbiter of the presence of NAFLD the authors
cannot state with any certainty that patients with a “normal” USS at the start of
the study have NAFLD or not. These patients may have mild steatosis which is
not detected on USS (as they themselves comment on in the discussion).
I accept that it would be impossible to MRI all these patients but non-the-less all
that can be said with certainty in this regard is that patients with the reported risk
factors are more likely to have moderate steatosis at 4.37 years of follow up than
those without risk factors.
There is, therefore, nothing to say that all 430 patients who developed “incident”
NAFLD over a mean of 4.37 years did not have some degree of fatty liver
disease at study outset. In this situation the data remains of use in tracking the
natural history of NAFLD but it is not permissable to say that the later finding of
USS features compatible with NAFLD represent a new finding.
2) Interestingly of the 4,463 apparently healthy patients screened by USS 1,242
were excluded due to prior fatty liver disease. This is over a quarter of the study
population and these patients should not be excluded. Consequently, the
prevalence of identified risk factors for the study in this cohort should be
reported. If the prevalence of these risk factor thresholds is the same as the
cohort with “normal” initial USS but who had features of NAFLD on subsequent
USS then again this dataset is useful at identifying risk factors for progression of
hepatic steatosis over time.
3) It is not clear from the manuscript how many of the 2,589 subjects with no fatty
liver on ultrasound received a follow up USS. If not all patients received a
follow-up USS the reasons why these patients received it should be explicitly
stated.
4) In the assessment of NAFLD the critical issue is not merely the identification of
simple steatosis but that of significant liver disease. In this respect the data
should be available to calculate a non-invasive fibrosis risk assessment (for eg
with the NAFLD fibrosis score). Use of such a disease severity tool would
improve the clinical utility of their findings.
5) When talking about preventing the need for expensive imaging tests the
authors should report by what proportion abdominal USS use could be potentially
decreased by the implementation of their combination risk factors. This however
has to be considered in the context of the number of patients with elevated ALT
levels as those patients would be justified in having an USS, irrespective of the
other risk factors.
Discretionary revisions:
1) The authors could emphasise more the role of their revised thresholds of the 5
parameters in improving the prediction of NAFLD by USS criteria. This seems
one of the strengths of this study. What is interesting is that the established
thresholds are good at excluding NAFLD whilst the revised ones are better at
identifying more marked steatosis.
2) I would take the “4.37 years” out of the title
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