Review for 10.1186/s12876-014-0213-y (2014)

Reviewer's report
Title:Gallstones associated with non-alcoholic fatty liver disease in female rather
than male: a longitudinal cohort study
Version:1Date:31 July 2014
Reviewer: Constance E Ruhl
Reviewer's report:
The authors conducted a prospective study of the relationship of nonalcoholic
fatty liver disease (NAFLD) with incident gallstone disease (GSD) among
Chinese who underwent routine health check-ups. They found a higher incidence
of GSD among persons with NAFLD and this association was limited to women.
NAFLD and GSD are both common conditions and only a limited number of
studies have examined their relationship and few of these have been
prospective. Strengths of this study are the prospective design and large sample
size. However, I have some concerns about the methodology (see below). In
addition, the paper needs to provide more detail, particularly with regard to the
methods, and has many errors in English usage.
Major Compulsory Revisions
Introduction:
1) 1st paragraph of background, last sentence – “…due to the pathogenic
mechanisms of gallstones formation hasn’t been ascertained”. This is not
accurate. Although the pathophysiology of GSD is not completely understood,
much is known with regard to the contributions of cholesterol supersaturation of
bile, pronucleating factors, and decreased gallbladder motility.
2) 2nd paragraph of background, 1st sentence – “NAFLD … plays an enormous
role in the prevalence of gallstone disease.” This is too strong a statement and is
made without references. If this was known to be true, there would have been no
need to do the study the authors have done.
Methods:
1) To help the reader to better assess generalizability, what is the geographic
area served by the 2 hospitals and what proportion of residents of that
geographic area underwent health check-ups at the 2 hospitals? How did the
health examinees compare with the general population of the geographic area,
i.e. higher socio-economic status, etc.?
2) Derivation of the study sample is important and should be described more fully
in the text, rather than merely shown in a supplemental figure.
3) An inclusion criterion was having undergone 3 or more health check-ups. Why
not include persons with any follow-up, i.e. >2 health check-ups? It is possible
that persons with more check-ups were more likely to have both NAFLD and
GSD which could potentially introduce bias. How comparable were persons
without follow-up to those with follow-up?
4) An exclusion criterion was “other known etiologic factors of chronic liver
disease”. What were these other factors?
5) Another exclusion criterion was “time sequence from GD to NAFLD”. It seems
like these persons should have been included and contributed non-NAFLD
person-time up until their diagnosis with GSD.
6) Do all persons undergo abdominal ultrasonography to check for GSD and
NAFLD as part of a routine health check-up each time they have one? What if a
person had a clinical diagnosis of GSD or NAFLD in between check-ups?
7) Only 4 cases of cholecystectomy seem like an extremely low rate. Is it typically
this uncommon in China? How was cholecystectomy defined?
8) NAFLD definition – what drugs were included in hepatotoxic drugs?
9) What was the extent of missing data before imputation and what proportion of
participants had imputed data? Were data imputed for GSD and NAFLD or only
for covariates?
10) Did the authors test for interaction between sex and NAFLD status?
Results:
1) Have the authors examined the relationship between prevalent NAFLD and
prevalent GSD in the entire sample who underwent a health exam before looking
at the longitudinal relationship? It would be useful to first know how this baseline
relationship compares with other cross-sectional studies.
2) How many participants had NAFLD at baseline and how many were
diagnosed during follow-up?
3) Table 1 – This table is very busy and not appealing to look at. It would be
more useful and standard to show the covariate means or percentages among
participants with and without NAFLD at baseline. The current table would be
more appropriate as a supplemental table.
4) Tables 2 & 3 – In Table 2, the event rate for women with NAFLD was 25 times
that of women without NAFLD. In Table 3 with age-adjustment, women with
NAFLD were 80% more likely to develop GSD (RR=1.8). This seems like a very
big difference between unadjusted and age-adjusted analyses.
5) 3rd paragraph of results beginning with “Table 2 …” - Last sentence does not
appear to agree with the numbers shown in Table 2.
Discussion:
1) Last sentence of discussion – What is referred to as “selection bias” is actually
decreased generalizability.
Minor Essential Revisions
Results:
1) Table 1 & text - When listing covariates, write out the actual name rather than
using the variable name, unless the variable name is a standard abbreviation
such as BMI.
2) Table 3 & text - There is no value in showing 4 digits following the decimal
point and it is distracting. Providing 2 significant digits following the decimal point
is sufficient and easier to read.
3) Table 3 – What covariates were included in multivariate-adjusted models
(show in a footnote).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
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.