Review for 10.1186/1471-230X-10-92 (2010)

Reviewer's report
Title:Infection with HIV and HCV enhances the release of Fatty Acid Synthase
into circulation: Evidence for a novel indicator of viral co-infection
Version: 1Date:1 February 2010
Reviewer: Qiang Liu
Reviewer's report:
Gerard Aragonès et al. evaluated the use of the level of circulating fatty acid
synthase (FASN) as an indicator for HIV and HCV co-infection. The major finding
of this work is that, in comparison to healthy individuals, the levels of FASN are
significantly higher in HIV-infected individuals and co-infection with HCV further
and significantly increases FASN. Since infections of both HIV and HCV have
been associated with metabolic abnormalities, characterization of FASN, a key
player in the host lipogenic pathway, is important for understanding pathogenic
mechanisms by these two viruses. As such, this article investigated an important
question. The experimental design, interpretation of the data, and discusion are
sound in general. However, the following points need to be addressed prior to its
acceptance for publication.
1. The impact of viral load on FASN levels? FASN levels are significantly higher
in HIV patients than healthy individuals (Figure 1A). Does this include subjects
with undectable and detectable HIV viral loads? If so, it would be interesting to
further compare the FASN levels between these two groups. As well, co-infection
with HCV further increases FASN with statistical significance (by the way, this
should be stated clearly in the second paragraph of the Results session). It would
be critical to include the information of HCV infections, such as viral loads and
genotypes because different HCV genotypes may play different roles in
modulating lipid metabolism.
2. The authors were not able to correlate the increased FASN levels with
expected changes in non-esterified fatty acids in HIV patients. Is this also the
case for HCV co-infections? The authors should perform this experiment which
will provide evidence supporting their hypothesis where they believe FASN
expression is regulated by a unique mechanism in HIV infection and not in HCV
infection (in the middle of the first paragraph in the Discussion).
3. In an effort to correlate FASN levels with inflammation, the authors measured
a number of markers such as IL-8 and MCP-1. HCV co-infection increases IL-8
levels but does not reach statistic significance (Fig. 2C). This seems at odd with
previous findings where the IL-8 levels are significantly higher in HCV infected
patients than healthy controls (e.g., Polyak, et al., JVI, 2001). Reasons for this
discrepancy should be discussed.
4. The authors have found increased MCP-1 levels which showed a good
correlation with FASN levels. While this seems to fit with the role of MCP-1 in
modulating lipogenesis, the lack of an effect of HCV infection on MCP-1
expression is somewhat puzzling (Fig. 2A). Once again, do the MCP-1 levels
correlate with HIV and/or HCV viral loads?
Minor point:
Please number the pages and lines.
Level of interest: An article of importance in its field
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.