Review for 10.1186/1471-230X-8-47 (2008)

Reviewer's report
Title:Bile composition in Alagille Syndrome and PFIC patients having Partial
External Biliary Diversion
Version: 1Date:21 May 2008
Reviewer: Ralf Kubitz
Reviewer's report:
Emerick et al., "Bile composition in Alagille and PFIC patients having partial
external biliary diversion":
General:
The manuscript "Bile composition in Alagille and PFIC patients having partial
external biliary diversion" describes three small groups of patients with different
forms of inherited cholestasis. All patients were treated by surgical bile drainage
in order to treat cholestasis-associated pruritus. Composition of bile samples was
analysed at the time of surgery and several months to years after surgery. The
study sought to define prognostic factors of clinical outcome after partial external
biliary diversion – which could not be detected. The major draw back of the study
is the small number within the three groups of patients.
Major points:
1. The three groups of patients are very small (3 or 4 patients per disease entity),
which may not be representative for the type of cholestasis. The group of PFIC-2
patients (with mutations of BSEP) were genetically different, whereas all four
PFIC-1 patients (mutations of FIC-1) belong to the same family with an identical
genetic background. Therefore, the "better" clinical course of PFIC-1 patients
after PEBD and changes in bile composition may be attributed to their particular
FIC-1mutation. On the other hand, no genetic information is given concerning the
AGS patients.
2. The definitions of "responders" and "non-responders" are overlapping: e.g. a
patient with bile salts below 40 µmol/l but with drop of pruritus score of 1 after
PEBD fits both definitions. Similar, "PFIC responders" (page 9) maintained "bile
acid levels of 40,9 +/- 53.9 µmol/l", thus, by author's definition, they can be
regarded as non-responders.
3. Considering that PFIC-1 and PFIC-2 patients substantially differ in respect to
changes in phospholipid content and CDCA/CA ratio (see figure 2) it seems not
justified to mix data of these two patient groups in order to differentiate
"responders" and "non-responders" (figure 3).
4. Discussion page 12: Which parameters were considered in order to identify
parameters as prognostic factors?
5. Conclusion: the first paragraph of this section does not conclude anything.
Secondly, the "confirmation" of earlier data is not a conclusion and thirdly, the
conclusion that larger studies are needed for "definite conclusions" is correct and
reflects the limitation of the study.
Minor points:
6. Page 5: "All patients ... medical therapy without success": Was unsuccessful
treatment defined as persistent pruritus or by biochemical parameters or just by
clinical judgment?
7. It is indicated, that bile samples represented gall bladder bile initially and
ostomy bile at follow up. It cannot be excluded that differences in bile
composition before and after surgery is partially due to "stasis effects", since
residence of bile within the gall bladder becomes modified with time. Did the
authors check if "flowing bile" right after surgery was similar to "stagnant bile"
from gall bladders?
8. Page 5: The "four-point scale", which was used to quantify pruritus, should be
described briefly. In the case that this method included patients rating it must be
considered that validity may vary considerably between small children (BSEP
group) and teenagers (AGS group).
9. IRB should be defined (Institutional review board).
10. Page 6: Was the pathologist really "blinded" or was the analysis done in a
blinded fashion?
11. Table 1: this table should contain bile salt concentrations.
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