Review for 10.1186/1471-230X-8-13 (2008)

Reviewer's report
Title:Prevalence and determinants of biochemical dysfunction of the liver in
Atayal aboriginal community of Taiwan: Is betel nut chewing a risk factor?
Version: 1Date:16 July 2007
Reviewer: Barbara J J Boucher
Reviewer's report:
General These remarks are in standard text below
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Major Compulsory Revisions (that the author must respond to before a decision
on publication can be reached)These comments are in BOLD
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Minor Essential Revisions (such as missing labels on figures, or the wrong use of
a term, which the author can be trusted to correct) These comments are in
ITALICS
Re MS Research article: - Prevalence and determinants of biochemical
dysfunction of the liver in Ataya aboriginal community of Taiwan: is betel chewing
a risk factor? Lin C-H et al.
This cross-sectional study appears to the first on this subject in an aboriginal
group in Taiwan though there are several papers on the topic in the population of
Taiwan including case-control studies, cross-sectional community based
observational studies and prospective studies examining numbers of habits in
relation to development of liver cirrhosis and HCC, especially in those with
chronic viral hepatitis. The findings from the data presented show associations
similar to those reported in other Taiwanese communities, providing a further
demonstration of the likelihood that this particular association of disease with the
betel habit is significant at the population level.
Comments: - General.
The numbers of non-Ataya subjects was small compared to the numbers of
subjects of Ataya origin so that some comparison of that data with the findings in
published data on similar non aboriginal groups would be useful for the betel data
[as already given for viral data] if the reader is to be able to appreciate the scale
of this particular betel-associated health problem in the aboriginal group.
There is no data shown for how long subjects had been betel chewers nor is any
data shown for how many chews subjects used/day. Since some betel habit
related risks appear to be dose-effects in Taiwan [in the KCIS published reports
[such as T2Diabetes Mellitus and metabolic syndrome] this data should be used
in analyses to see if the liver problems identified as being associated with betel
chewing may also show dose-effects. If this data is not available this should be
stated in methods and referred to as a weakness of the study in the Discussion
section.
There is no data that I have seen on which body gave permission for the study to
be carried out. Was consent ‘informed’ and if so was information provided both
orally and in writing or not and, if in writing, in what language bearing in mind that
the aboriginals may not have spoken the same language as the researchers!
Should the term Aboriginal not be given a capital each time it appears?
Detailed comments by section.
Essential minor revisions in italics
Essential major revisions in bold.
Discretionary revisions in standard text.
Abstract. Results, it would help to give the numbers of subjects (in brackets) after
‘Aboriginal’ and ‘non-aboriginal’. The sentence starting ‘The adjusted odds ratios
of chewing betel etc reads as if this was analysed the other way around, i.e., OR
for increased ALT/AST in chewers. Does this in fact mean ‘Adjusted ORs for
betel chewing in those with increased ALT or AST were …’ or does it mean
‘Adjusted ORs for abnormally raised ALT and AST in betel chewers were …’?
The sentence on those agreeing to liver ultrasonography is unclear, does this
mean ‘Among 1.282 subjects consenting to abdominal ultrasonography,
41(3.0%) were found to have liver cirrhosis? The last sentence says ‘…probably
liver cirrhosis’, but does this mean ‘..biochemical dysfunction likely to be
associated with an increased risk of liver cirrhosis.’?
Background. Page 4. Line 1, ‘have been’ would read better than ‘were’. Para 2,
Line 4, ‘A more recent investigation…’would be better than ‘A more updated
investigations…’ if this refers to a single study. Page 5. Line 1. ‘estimated at
about’. Lines 2-3. This confused sentence could be simplified ‘Thus, abnormal
liver function in aboriginal people in Taiwan has usually been considered to be
virus or alcohol related’. Describing betel quids used in Taiwan, the proper name
of the palm, Areca catechu, should be mentioned once, in italics as is usual and
also, is the Piper betel leaf used in the Ataya community rather than the
inflorescence used in Taipei? Re the sentence using ref 14; including the
reference describing targeting of arecal nitrosamines to tissues of foregut origin
when given intravenously might be useful. This may be in a paper by Nair and
Nair. Last Para, Line 2, omit ‘a’, Last line, would read better as ‘this habit’ rather
than ‘such a habit’
Methods. Page 7. Line 2, does this mean ..’in the eastern plains and central
mountainous area…’
Line 4. ‘….which is located in …’. Line 8, this is the only mention of the Hakka
tribe. If there are Hakkas in the study group the numbers should be given and
you should report whether the findings appear to be comparable or not in the 2
aboriginal groups.
Data analysis, Para 2, 1st sentence, Testing for Hbs Ag …. Etc.
Page 8. line 1, if the reading was borderline … Line 2-3. ‘Liver function tests were
performed…’Line 5. Diagnostic imaging for liver disease …. This sentence
should be followed by the criteria used to diagnose liver cirrhosis with a
reference.
Line 7. ……and previous medical history, ethnic group etc. Line 12, ‘generally
accurate’ is not adequate. The Authors should give some estimate of accuracy.
It is unclear whether non-normally distributed data was normalized before use in
regression analyses and this should be clarified.
Last word, ‘status’ would be better than ‘condition’.
Results. Page 9, 6, ‘resident’ would read better than ‘stayed’. Line 7, omit ‘about’.
Line10, For clarity: - ‘…18.2% showed an abnormal AST and 28.6% an abnormal
GGT.’
11, ‘those of’ should read ‘did’.
The data for the non-aboriginal groups and the non-aboriginal group should be
shown together, perhaps in a Table, with numbers of subjects and % findings so
that the validity of the comparisons with this ‘control’ group can be examined by
readers, then it can be seen whether the liver related abnormalities are more
common in the aboriginals and valid differences can then be identified (p<0.0-).
Last Line Para 1. ‘Table 2 summarizes the ….’ Page 10. Line 3, …with an OR for
ALT of …, for AST of … and for GGT of …’ or some suitable re wording needed
to make this easier to follow as would saying ..Increased BMI (>25) was also
associated with increased risks for abnormality in ALT and GGT [This finding
could be due to the non alcoholic fatty liver disease seen in obesity; therefore this
point should be referred to in the discussion when discussing potential
confounders; both those allowed for and those not allowed for.
Para 2, line 2, it would be better to say ‘with liver cirrhosis’ or ‘with cirrhosis of the
liver’ than ‘cirrhosis of liver’ which is an incomplete remark. The last sentence of
this page is redundant here as it is entirely speculative, any such remarks are for
the discussion. Page 11. Line 1. Insert’ for’ after ‘controlling’’
Discussion. Page 12, Line 2, ‘higher than in non-aboriginals..’. Line 3-4 ‘’’,
especially using a cross-sectional design, requires careful evaluation’ Line 5,
‘’and sightseeing which attracted ….’Line 7. ‘to compare the findings in these
ethnic groups’.
Weaknesses of the study should follow on here and, where they can be shown to
be unlikely to have confounded the study the reasons for this should be stated
include those identified or queried in the above report; the possible errors in data
collection, including ethnicity in view of free care for aboriginals [since others may
have claimed aboriginal status for this reason]. The possibility of random errors
next, as already in the paper,
Strengths of the study should be stated next including the comparable uptake of
NHI by each ethnic group’’.
Page 13. Line 5, ..Tables 2 and 3, supporting the validity of the findings in this
study. Lines 9-10,The last part of this sentence needs to be rephrased; perhaps
to ‘…including betel chewing. Efforts to reduce the prevalence of liver disease in
aborigines should, therefore, include efforts to increase quitting of the betel habit.
Line 11 to end of page needs to be shortened and to be put more simply while
stating that the associations described between betel chewing and liver disease
imply that there may a causal role for this habit. e.g. ‘This could reflect the effects
of betel quid components such as .. which induces .. ,or … which causes …. etc.
Line 14, ref 21 specifically refers to anti-bacterial role of WBCs not anti-viral; is
there a better ref to use? Last line, re refs 23/24, …other reactive oxygen
adducts formed as a result of habitual betel chewing’ or some similar wording
would aid clarity.
Page 14. Lines1-2, high proportion (up to 37.5%) of betel quids contaminated by
aflatoxin, …’ Lines 2-3, try to clarify; ‘..Further studies are needed to determine
which components of betel quids may be responsible for liver damage are now
required.’
Lines 5-6, has been isolated from betel nuts (32) ? Para 2, Line 4. ..it is difficult to
hypothesize what the combined effects of eating Piper betle vines, +/- Areca
catechu, may be. Lines 6-7 on confounding might best be moved back to the
suggested section on confounders? The last Para on this page, and overleaf,
seems to repeat the thinking in Para 1; on Page 14, last sentence would itself
make a nice ending to this discussion. Could the authors, therefore, consider
combining these remarks into one Para at the end of the Discussion. This final
Para should focus on reduction in betel chewing rates in Aboriginals for reduction
in the risks of liver disease rather than on all the other aspects of increasing
uptake of health care that are lumped together in the present final paragraph?
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Discretionary Revisions (which the author can choose to ignore)
I now see that your format does not recognise bold or italics which makes it
difficult. I will e mail teh file with the format in full to teh journal adn ask them to
forward it to both teh editorial team and the authors.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I have no financial or other competing interests such as are listed above though I
am involved in writing up work in this area with others in Taiwan. I do not,
however, beleive that this research interest has in any way predjudiced my
preparation of this report.