Here, we propose a novel mechanism for enhanced HCVrelated liver disease progression in HIV co-infection; that of bystander activation and induced inflammation from HIV-specific T-cells accumulated in the liver. Our data however are limited in the cross-sectional nature of our cohort, the low number of analyzed liver biopsies and the narrow range of CD4 + T-cell counts among the studied individuals. We should also acknowledge that ex-vivo functional T-cell capacity may not exactly reflect the situation in-vivo. Further studies, particularly, those which are prospective are warranted in order to understand the role that HIV-specific T-cells play in contributing to fibrosis and in particular how HAART modulates these responses. frequency of CD8 + T-cells specific for HCV, HIV and CMV in HCV/HIV co-infected liver (OM 385). Liver isolated mononuclear cells were stained with pools of HLA-A*0201 and HLA-A*2402-restricted pentamers (Pro5 MHC class I Pentamers, Proimmune), followed by staining for cell surface markers CD3 and CD8. The following pentamers were used for each group: HCV pentamers: NS3-CINGVCWTV and NS3-KLVALGINAV; HIV pentamers: Pol-ILKEPVHGV and Gag p24-TLNAWVKVV; CMV Pentamers: pp65-NLVPMVATV and pp65-QYDPVAALF. No CD8 + T-cells specific for CMV were detected in this co-infected liver sample. Similar findings were found in another individual (data not shown). doi:10.1371/journal.pone.0003454.g004 background is shown to become extremely low when examining combinations of functions, nearly reaching 0 events for multiple functions simultaneously. This permits a very low threshold for detection of positive responses from multiple combinations. Consequently, for multi-parameter analysis, the results were thresholded based on a minimum criterion of positivity, as calculated by SPICE software and presented as the 90 th percentile of negative values for each analysis. Each pie chart generated by SPICE software, represents the hierarchy of responses to either HCV or HIV antigen stimulation. For simplicity, responses are grouped by number of functions and matched to the colored bars, with black bars representing the percentage of responding cells to HIV peptides and gray bars representing the percentage of responses to HCV peptide stimulation. In all pie charts, color red represents the 5+ responding population and the colors blue, green, turquoise, and yellow representing the 4+, 3+, 2+, and 1+ populations respectively. Color-coded arcs represent the dominant marker within each pie slice, with color blue representing TNF-a, red for CD107-a, green for IFN-c and black for MIP-1b. Although IL-2 is included in the presentation and demonstrated by bar graphs, the software would not allow for arc colors for more than 4 responses. As a result there is no arc representative for IL-2. Figure (c) represents the average frequency of intra-hepatic viral specific responses within the pool of CD8 + T-cell populations simultaneously expressing 2 functions or less, compared with those within the pool of populations expressing more than 2 functions simultaneously; as analyzed in 3 subjects within each cohort of HCV mono and HCV/HIV co-infected individuals. The cutoff point of simultaneous expression of more than 2 measured markers is considered to show CD8 + T-cell poly-functionality.  Multiorgan failure due to hemophagocytic syndrome: A case report INTRODUCTION: Hemophagocytic syndrome (HFS) is a potentially lethal disorder due to an uncontrolled immune response to a triggering agent. Our objective is to raise the importance of HFS early diagnosis by presenting a representative case. CASE PRESENTATION: A sixteen-year-old girl with Still disease diagnosis developed a progressive multiorgan failure including acute respiratory distress (ARDS), anemia and thrombopenia, elevated liver enzymes, renal failure, coagulopathy with hypofibrinogenemia, and acute phase reactants elevation despite broad-spectrum antibiotics. A bone marrow puncture-biopsy was performed, and hemophagocytosis was found. Prolonged fever, splenomegaly, bicytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia confirmed HFS diagnosis. She received intensive care support therapy including mechanical ventilation and specific therapy according to HLH 2004 protocol, with a very good response. CONCLUSION: Our case shows complexity of HFS diagnosis, due to septic shock-like manifestations. Early diagnosis is essential to start appropriate treatment achieving a better outcome. Hemophagocytic syndrome (HFS) is a rare disorder characterized by prolonged fever, cytopenias, hepatosplenomegaly, hypertriglyceridemia, disseminated intravascular coagulation (DIC)-like coagulopathy and bone marrow, spleen, liver or lymphatic nodes histiocytosis [1] [2] [3] . A sudden presentation, like a septic shock is possible making its early recognition a challenging diagnosis [4] . It is well known that HFS could be a severe complication in some infections (mainly virals) or in some underlying diseases, such as chronic juvenile arthritis (CJA) [3, 5, 6] . Moreover, it is one of the differential diagnosis in fever of unknown origin [7] .