Abstract
INTRODUCTION. Acute liver failure (ALF) is a devastating condition with a mortality >40% despite transplantation. It is characterized by overwhelming
hepatocyte death inducing a systemic inflammatory response (SIRS). SIRS moreover confers adverse outcome. Monocytes/macrophages have been implicated as
key effectors of SIRS in the pathogenesis of ALF (1,2). Novel therapeutic strategies to ameliorate acute liver injury are desirable. A multicentre study demonstrated a
20% survival benefit in patients treated with therapeutic plasma exchange (TPE) (3). TPE is an established therapy used for various immunologically driven
disorders. Its mechanism of action is unclear but recent data highlight its ability to dampen pro-inflammatory responses of monocytes (4).
OBJECTIVES. To determine the immune-modulatory effect of TPE on monocytes in patients with ALF as a pathogenic proof of principle for its possible
therapeutic benefit.
METHODS. The pilot study included 7 patients with ALF (n=3 undergoing early TPE, (day1 after admission); n=1 late TPE (day3); n=3 without intervention).
Healthy peripheral blood mononuclear cells were cultured for 24 hours in medium containing 25% plasma from ALF patients. The effect of plasma obtained before,
after TPE and after 5-8 days was compared to the effect of plasma from patients who did not undergo TPE. TNF-? and IL-6 production of monocytes in response to
lipopolysaccharide (LPS) was assessed by flow cytometry based intracellular staining.
RESULTS. ALF plasma induced monocyte death in vitro in relation to disease severity. Pro-inflammatory cytokine production of monocytes was markedly reduced
after incubation with plasma from ALF patients following early TPE compared to plasma preceding TPE: TNF-? was significantly suppressed (mean MFI 1936 vs.
651, p=0.0012); IL-6 was numerically lower (mean MFI 3676 vs. 1834, p=0.1349). Sequential plasma samples from patients with ALF following late TPE or natural
course of disease did not modify TNF-? or IL-6 production differentially.
CONCLUSIONS. Clearance of accumulating mediators from the plasma by TPE modulated monocyte function towards anti-inflammation in vitro. TPE might
therefore alleviate SIRS and extrahepatic organ dysfunction with possibly beneficial effects on outcome if introduced in early phases of ALF.
REFERENCES.
1. Antoniades CG et al., Hepatology, 2006; 44:34-43;
2. Antoniades CG et al., Hepatology, 2014; 59(4):1564-76;
3. Larsen FS, et al., Hepatology, 2010; 52(4)S, 376a;
4. Winters JL, Am. Soc. Hematol. Educ. Program, 2012:7-12.
GRANT ACKNOWLEDGMENT. European Society of Intensive Care Medicine, European Association for the Study of the Liver, Medical Research Council,
Rosetrees Charitable Trust.
| Original language | English |
|---|---|
| Pages (from-to) | S30-S30 |
| Number of pages | 1 |
| Journal | Intensive Care Medicine |
| Volume | 40 |
| Publication status | Published - Sept 2014 |
| Event | 27th Annual Congress of the European-Society-of-Intensive-Care-Medicine (ESICM) - Barcelona, Spain Duration: 27 Sept 2014 → 1 Oct 2014 |